# Biotin — sole-added-active oral product × Lower HbA1c in adults with type 2 diabetes Verdict 3105 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-15 Review-criteria version: NGM-v3105-SOLE-BIOTIN-T2D-HBA1C-1.0 Public page/material preparation date: 2026-11-03 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Adults with type 2 diabetes; confirmed deficiency correction, type 1, gestational and drug-induced diabetes, prediabetes and healthy populations are separate; unreported biotin status is not presumed normal - Ingredient, formulation and route: Biotin (biotin, vitamin B7), sole added active ingredient · The question is bounded to an oral product with a sole active ingredient; eligible product formulation, excipients, batch and purity are unverified · Oral; topical and injectable routes excluded - Dose: Unverified — dose, frequency, dietary intake and total concurrent supplemental intake for an eligible regimen - Comparator: Placebo, no biotin supplement or usual care under the same background conditions; the actual eligible comparator is unverified. Maintaining common diabetes treatment is a separate condition - Measured outcome: Priority is given to the between-group HbA1c change difference (%p) at a prespecified follow-up; an appropriately adjusted between-group endpoint contrast is separate. FPG, PPG, insulin, HOMA-IR and fructosamine are not substitutes - Duration: Unverified — eligible treatment duration and prespecified HbA1c follow-up - Questions outside this scope: Common metformin is allowed; mixtures with a concurrent change in chromium, confirmed deficiency correction, type 1/gestational/healthy populations, FPG/PPG/Hb and clinical events/assay bias are separate. The candidate GUTERRING biotin-only arm is retained. /subclaims=[] ## Checklist items ### N01 · Which biotin, population and HbA1c comparison does the question concern? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The selected question asks whether oral biotin as the sole added active ingredient in adults with T2D lowers HbA1c at a prespecified follow-up compared with placebo, no supplement or usual care under identical background treatment. subclaims is an empty list. - Why unverified: This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide. - Reason for missing information: This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide. - Required materials and conditions: Adults with T2D · Oral biotin as the sole addition · Comparator with identical background conditions · Between-group HbA1c result at a prespecified time point - Materials to obtain first: Adults with T2D · Oral biotin as the sole addition · Comparator with identical background conditions · Between-group HbA1c result at a prespecified time point - Further research: For each source, compare the direct comparison results that match this question and the reasons for any mismatch. - Conditions for verification: Link the current original effect wording to the actual inclusion/exclusion boundaries and original pointers. - Why this condition is needed: Needed to avoid combining the ingredient as a whole or all glycemic markers into a single result. - Application exceptions: Type 1/gestational/healthy populations, confirmed deficiency correction, topical/injectable routes and concurrent changes in chromium are separate. - Remaining uncertainty: This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide. - Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed - Related sources: S01, S02, S04, S05, S10, S11, S15 ### N02 · Does common metformin treatment exclude a comparison of a sole added ingredient? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S11 is a candidate in which only biotin was added to the common treatment of metformin 500 mg/day in both arms, so it is not excluded because of concomitant treatment. The endpoint actually verified is not HbA1c. - Why unverified: This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained. - Reason for missing information: This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained. - Required materials and conditions: Background treatment in both arms, added ingredients, arm-specific changes/rescue treatment and the actual effect of interest - Materials to obtain first: Background treatment in both arms, added ingredients, arm-specific changes/rescue treatment and the actual effect of interest - Further research: Compare results in which only biotin differs under identical background treatment, along with changes in diabetes medications. - Conditions for verification: Distinguish the difference in added ingredients from common treatment and link this distinction to endpoint eligibility. - Why this condition is needed: Common treatment must be distinguished from active ingredients that change concurrently. - Application exceptions: A comparison of biotin as the sole addition is not excluded merely because it is described as concomitant treatment. - Remaining uncertainty: This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S11 ### N03 · Are the chemical form, origin and manufacturer of the directly eligible product known? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: exact_chemical_form and manufacturing_origin have null value entries/not_verified. source_part also leaves the chemical form, origin and manufacturer of the eligible preparation unverified. - Why unverified: The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted. - Reason for missing information: The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted. - Required materials and conditions: Exact chemical form, origin, manufacturer and documentation verifying the active ingredient - Materials to obtain first: Exact chemical form, origin, manufacturer and documentation verifying the active ingredient - Further research: Obtain and link the original product documentation and manufacturing specifications for the eligible result. - Conditions for verification: Separate verified values for the directly eligible product from null values and reasons for nonverification. - Why this condition is needed: Needed to avoid filling in the identity of an eligible HbA1c regimen with a product from another study. - Application exceptions: Naming biotin in the question does not verify the chemical form of the actual preparation. - Remaining uncertainty: The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed - Related sources: S01, S02, S04, S11, S15 ### N04 · Are tablet/capsule form, excipients, brand, batch and purity verified? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: tablet_or_capsule, excipients, brand and batch_purity all have null values/not_verified. An oral product with a sole active ingredient is the question boundary, not the specifications of an actual eligible product. - Why unverified: Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available. - Reason for missing information: Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available. - Required materials and conditions: Formulation, excipients, brand, batch/purity and other added active ingredients - Materials to obtain first: Formulation, excipients, brand, batch/purity and other added active ingredients - Further research: Compare the preparation specifications and batch documentation for the eligible comparison. - Conditions for verification: Identify the actual locations verifying the eligible formulation and composition/quality, or mark them as unverified. - Why this condition is needed: Needed to avoid claiming identical composition and quality based solely on a product name. - Application exceptions: Specifications of a combination product are not transferred as verification of a sole-active product. - Remaining uncertainty: Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed - Related sources: S01, S02, S04, S11, S15 ### N05 · What are the eligible biotin dose, frequency and total exposure? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: dose, frequency, dietary_biotin and concurrent_supplements have null values/not_verified for the directly eligible comparison. S11's 5 mg 2 times daily is the exposure in a candidate study of another endpoint. - Why unverified: The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials. - Reason for missing information: The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials. - Required materials and conditions: Eligible dose/frequency, dietary biotin, concurrent supplements and actual exposure - Materials to obtain first: Eligible dose/frequency, dietary biotin, concurrent supplements and actual exposure - Further research: Link the relevant product, dose, frequency and dietary/supplement records to the eligible result. - Conditions for verification: Explain what is verified and what is missing about the actual dose and total exposure linked to the selected result. - Why this condition is needed: Needed to avoid using quantities from adjacent FPG studies or safety cases as an HbA1c regimen. - Application exceptions: Do not arbitrarily convert values expressed in mg, µmol and µg at different source locations into mass equivalents. - Remaining uncertainty: The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details of dose, duration and effect modification are internally designed - Related sources: S01, S02, S05, S06, S11 ### N06 · Have the treatment duration and HbA1c follow-up time been specified? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: treatment_duration and followup_time have null values/not_verified. S11 used 4 weeks of biotin treatment followed by 2 weeks of observation off biotin, while S05 used a combination product for 90 days; neither fills in the eligible HbA1c duration. - Why unverified: The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long. - Reason for missing information: The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long. - Required materials and conditions: Actual treatment duration, prespecified follow-up time and separate post-discontinuation time point - Materials to obtain first: Actual treatment duration, prespecified follow-up time and separate post-discontinuation time point - Further research: Compare the direct comparison's plan, treatment duration and results at each follow-up time point together. - Conditions for verification: Link the eligible treatment duration and prespecified HbA1c follow-up to the original plan/results. - Why this condition is needed: Needed to avoid transferring FPG at 4/6 weeks or a combination product at 90 days into the same HbA1c time point. - Application exceptions: Do not arbitrarily adopt a common minimum treatment duration. - Remaining uncertainty: The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details of dose, duration and effect modification are internally designed - Related sources: S05, S11 ### N07 · Are confirmed T2D diagnosis, baseline HbA1c and disease duration verified? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The question concerns adults with T2D, but diagnostic_criteria, baseline_HbA1c and disease_duration have null values for the directly eligible comparison. Materials on other populations are retained, with direct attribution restricted. - Why unverified: An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison. - Reason for missing information: An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison. - Required materials and conditions: Diagnostic criteria, age, baseline HbA1c, disease duration and population composition - Materials to obtain first: Diagnostic criteria, age, baseline HbA1c, disease duration and population composition - Further research: Compare recruitment, diagnosis, baseline tables and population composition for the eligible result. - Conditions for verification: Link the actual eligible population/baseline composition to the unverified items. - Why this condition is needed: Needed to avoid filling in the actual baseline status of the eligible sample from the population label alone. - Application exceptions: Type 1, gestational and drug-induced diabetes, prediabetes and healthy populations are retained as separate questions. - Remaining uncertainty: An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed - Related sources: S01, S02, S04, S10, S11 ### N08 · Have observations of low biotin been recast as confirmed deficiency correction? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: baseline_biotin and deficiency_assay have null values for the eligible comparison. The original KO explicitly states that observations of low circulating biotin were not recast as a trial treating confirmed deficiency. - Why unverified: The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified. - Reason for missing information: The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified. - Required materials and conditions: baseline_biotin, deficiency_assay, deficiency definition and eligible status - Materials to obtain first: baseline_biotin, deficiency_assay, deficiency definition and eligible status - Further research: Link the deficiency definition/assay to the direct HbA1c results for each relevant population. - Conditions for verification: Separate the status verified by the original source from the level of diagnosis that remains unverified. - Why this condition is needed: Needed to distinguish blood-level observations, unreported status and treatment of confirmed deficiency. - Application exceptions: Unreported status is not presumed normal, and a trial is not described as treating deficiency solely because low levels were observed. - Remaining uncertainty: The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed - Related sources: S01, S02, S04 ### N09 · Were between-group HbA1c changes distinguished from other glycemic outcomes? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: Priority is given to the between-group HbA1c change difference (%p), and an appropriately adjusted between-group endpoint contrast is separate. The original crux/content block and facets rule out substitution with FPG, PPG or other metabolic markers. - Why unverified: This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained. - Reason for missing information: This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained. - Required materials and conditions: Prespecified between-group HbA1c change difference in %p, adjusted endpoint contrast and measurement/analysis definitions - Materials to obtain first: Prespecified between-group HbA1c change difference in %p, adjusted endpoint contrast and measurement/analysis definitions - Further research: Compare the original plan with the change/endpoint estimates in the actual HbA1c tables. - Conditions for verification: Attribute observations to the selected endpoint, unit, time point and analysis. - Why this condition is needed: Needed to avoid interpreting FPG/PPG, insulin, HOMA-IR, fructosamine or Hb as HbA1c. - Application exceptions: Do not automatically equate an adjusted endpoint contrast with a change difference. - Remaining uncertainty: This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S01, S02, S04, S11 ### N10 · Are the HbA1c assay method and red-cell-related factors verified? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: HbA1c_assay, HbA1c_interference, anemia_RBC_lifespan, transfusion_hemoglobin_variant and renal_function have null values/not_verified. - Why unverified: Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review. - Reason for missing information: Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review. - Required materials and conditions: HbA1c assay, interference, anemia/RBC lifespan, transfusion/Hb variants and renal function - Materials to obtain first: HbA1c assay, interference, anemia/RBC lifespan, transfusion/Hb variants and renal function - Further research: Compare the assay principles, validation materials and baseline hematological/renal records for the eligible result. - Conditions for verification: Explain the actual assay method and arm-specific measurement conditions for the selected HbA1c outcome, and what remains unverified. - Why this condition is needed: Needed to distinguish changes in measured values from assay/red-cell conditions. - Application exceptions: Biotin interference in specific immunoassays is not generalized to all HbA1c methods. - Remaining uncertainty: Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are internally designed - Related sources: S01, S02, S04, S06, S07, S11 ### N11 · Is there an eligible between-group HbA1c estimate for biotin alone? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: between_group_effect, P and CI have null values for the directly eligible comparison. The assessment's direct_eligible_human_result_verified=false is a bounded gate for the fixed question. related_human_studies_exist=true is also retained. - Why unverified: Positive combination-product and FPG results are not substituted, and null values are not converted to 0. - Reason for missing information: Positive combination-product and FPG results are not substituted, and null values are not converted to 0. - Required materials and conditions: Directly eligible between-group HbA1c effect, follow-up time point, denominator and original result location - Materials to obtain first: Directly eligible between-group HbA1c effect, follow-up time point, denominator and original result location - Further research: Verify the between-group effect and its definition/time point in the eligible original result. - Conditions for verification: Link the direct estimate or an explicit gap within the currently verified scope. - Why this condition is needed: Needed to distinguish the existence of related human studies from obtaining a direct result for this question. - Application exceptions: Failure to verify a direct result is not described as an effect of 0 or an absence of human studies worldwide. - Remaining uncertainty: Positive combination-product and FPG results are not substituted, and null values are not converted to 0. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and internal design; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S01, S02, S04, S05, S11, S15 ### N12 · Can the effect magnitude be interpreted using CI, P and MCID? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: CI, P and MCID all have null values/not_verified for the eligible HbA1c comparison. P=.03 for the chromium-combination product is not used to construct an interval or importance assessment for biotin alone. - Why unverified: This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence. - Reason for missing information: This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence. - Required materials and conditions: Direct effect, confidence interval, variance, denominator and justified importance threshold - Materials to obtain first: Direct effect, confidence interval, variance, denominator and justified importance threshold - Further research: Compare the direct result's estimate, CI and basis for the MCID together. - Conditions for verification: Distinguish reported direct intervals/importance thresholds from the reasons interpretation is not possible. - Why this condition is needed: Needed to avoid equating a P value with clinical importance or precision. - Application exceptions: Do not arbitrarily set a minimum sample size, number of trials or numerical HbA1c importance threshold. - Remaining uncertainty: This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M15 §15.3.1–15.3.3; internal application - Related sources: S05 ### N13 · Are the allocation, completion, analysis and ITT/PP denominators linked? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: randomized_n, completed_n, analysis_n and ITT_PP have null values for the directly eligible comparison. S11's 60 allocated participants, 28 and 26 completers by arm, and 60 participants in the flowchart are records for other endpoints. - Why unverified: An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants. - Reason for missing information: An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants. - Required materials and conditions: Direct randomized/completed/analysis n, ITT/PP and reasons for/handling of missing data - Materials to obtain first: Direct randomized/completed/analysis n, ITT/PP and reasons for/handling of missing data - Further research: For each eligible result, compare the recruitment→allocation→completion→analysis flow and handling of missing data. - Conditions for verification: Show the actual denominator and handling for the relevant HbA1c outcome, or mark them as unverified. - Why this condition is needed: Needed to avoid using allocation or completion counts from another endpoint as HbA1c denominators. - Application exceptions: Do not sum n across different reports or arbitrarily reconcile flowchart conflicts. - Remaining uncertainty: An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S11 ### N14 · Are allocation, concealment and baseline balance known for the direct HbA1c result? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The retained evidence reports adjacent designs, including randomized blinded studies in S02/S04 and a single-center computer-randomized open-label trial in S11. The link between a directly eligible HbA1c result and its design is unverified. - Why unverified: The reference to trial_families.json in evidence does not mean that the file was read in this review. - Reason for missing information: The reference to trial_families.json in evidence does not mean that the file was read in this review. - Required materials and conditions: Actual eligible comparison design, randomized/nonrandomized allocation, concealment and baseline balance - Materials to obtain first: Actual eligible comparison design, randomized/nonrandomized allocation, concealment and baseline balance - Further research: Compare the protocol/allocation documents and baseline tables for the direct comparison. - Conditions for verification: Distinguish the verified design information for the selected result from the scope that remains unverified. - Why this condition is needed: Needed to avoid transferring a description of an adjacent randomized study as verification of the design for the selected HbA1c result. - Application exceptions: An unverified design is not labeled as crossover/cluster inapplicability or an automatic failure on bias. - Remaining uncertainty: The reference to trial_families.json in evidence does not mean that the file was read in this review. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M08 §8.1–8.2.3; internal application - Related sources: S02, S04, S11 ### N15 · Are actual adherence, diabetes medication changes, diet and exercise known? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: adherence, background_diabetes_medication, medication_change_rescue and diet_exercise have null values/not_verified for the directly eligible comparison. These are separate verification items from the nominal common metformin exposure in S11. - Why unverified: Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study. - Reason for missing information: Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study. - Required materials and conditions: adherence, background meds, rescue/change, diet/exercise and handling in the analysis - Materials to obtain first: adherence, background meds, rescue/change, diet/exercise and handling in the analysis - Further research: Link adherence, rescue-treatment and arm-specific change records for the eligible original result. - Conditions for verification: Explain arm-specific concurrent changes and adherence in the eligible comparison, and the gaps. - Why this condition is needed: Needed to separate concurrent changes from biotin's contribution. - Application exceptions: Verify the actual effect of interest and the handling methods rather than requiring all changes to be identical. - Remaining uncertainty: Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study. - Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S11 ### N16 · Were the planned HbA1c outcome, analysis and time points compared with what was reported? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S13/S14 are registry shells, and S15 is an indexed excerpt/shell. The historical limitation that some registry record texts, histories, protocols and SAPs could not be adequately obtained is explicitly stated in KO. - Why unverified: Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0. - Reason for missing information: Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0. - Required materials and conditions: Registry record text, history, protocol, SAP, actual results and reasons for changes - Materials to obtain first: Registry record text, history, protocol, SAP, actual results and reasons for changes - Further research: Compare the eligible candidate's registry history and original plan with the actual results. - Conditions for verification: Identify the locations showing what was actually compared and the plans/time points not compared. - Why this condition is needed: Needed to distinguish a registry shell from verification of the original plan. - Application exceptions: Failure to obtain material is not recast as confirmed nonregistration or selective reporting. - Remaining uncertainty: Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0. - Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application - Related sources: S13, S14, S15 ### N17 · Were Maebashi's fasting-glucose findings transferred to HbA1c? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F01/S01 concern fasting-glucose and circulating-biotin results, not between-group HbA1c results. The original KO did not recast the observed low levels as a trial treating confirmed deficiency. - Why unverified: The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time. - Reason for missing information: The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time. - Required materials and conditions: Maebashi’s actual population, ingredient, comparator, time point and endpoint, and whether a between-group HbA1c result exists - Materials to obtain first: Maebashi’s actual population, ingredient, comparator, time point and endpoint, and whether a between-group HbA1c result exists - Further research: Verify S01’s actual HbA1c results/plans during an authorized update. - Conditions for verification: Link the originally retained S01 results to the reason for exclusion from direct evidence. - Why this condition is needed: Needed to distinguish the existence of biotin-only studies from an eligible HbA1c result. - Application exceptions: Do not reclassify observations of low circulating biotin or the long-term combination arm as a sole-biotin comparison treating confirmed deficiency. - Remaining uncertainty: The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S01 ### N18 · Is Báez-Saldaña’s baseline glycated hemoglobin a follow-up effect? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F02/S02/S03 contain baseline glycated hemoglobin and enzyme/other metabolic-marker data; an eligible between-group HbA1c change/endpoint effect was not verified. The evidence field reports a randomized, blinded 28-day protocol after a cross-sectional phase. - Why unverified: Verifying a study’s existence and baseline values does not establish a direct follow-up effect. - Reason for missing information: Verifying a study’s existence and baseline values does not establish a direct follow-up effect. - Required materials and conditions: Baseline and follow-up HbA1c; the 28-day comparison; table/analysis definitions - Materials to obtain first: Baseline and follow-up HbA1c; the 28-day comparison; table/analysis definitions - Further research: Verify the HbA1c follow-up contrast, denominator and time point in the original results tables. - Conditions for verification: Distinguish S02’s baseline/other results from the unverified eligible effect. - Why this condition is needed: Needed to avoid misreading baseline characteristics as an estimate of between-group change. - Application exceptions: Do not recast enzyme or metabolic markers as between-group HbA1c follow-up results. - Remaining uncertainty: Verifying a study’s existence and baseline values does not establish a direct follow-up effect. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S02, S03 ### N19 · Were the location-specific values in the µmol/day erratum preserved? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: KO preserves the correction of 6.14 µmol/day to 61.4 µmol/day at several daily-dose locations and the 20.5 µmol/day notation at another specified location. S02/S03 belong to one study-and-erratum family. - Why unverified: The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0. - Reason for missing information: The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0. - Required materials and conditions: Relevant locations in the original text and erratum; the 6.14/61.4/20.5 µmol notations; the relationship between versions - Materials to obtain first: Relevant locations in the original text and erratum; the 6.14/61.4/20.5 µmol notations; the relationship between versions - Further research: Verify the original bytes, locations and versions of the original text and erratum, and update each exposure record. - Conditions for verification: Link the location-specific correction notations and remaining identity/interpretation limitations to the original text. - Why this condition is needed: Needed to avoid creating a new dose by ignoring the erratum or standardizing the values to a single value. - Application exceptions: Do not turn unclear locations or units into arbitrary mg conversions or personal prescriptions. - Remaining uncertainty: The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: S02, S03 ### N20 · Are Revilla-Monsalve’s lipid/glucose results HbA1c? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F03/S04 is a 28-day randomized, blinded placebo comparison with lipid, fasting-glucose and insulin results. Between-group HbA1c results were not verified in the original material. - Why unverified: The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL. - Reason for missing information: The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL. - Required materials and conditions: S04’s actual lipid, FPG and insulin results, and eligible between-group HbA1c results - Materials to obtain first: S04’s actual lipid, FPG and insulin results, and eligible between-group HbA1c results - Further research: Verify S04’s original plan/results tables for the presence of eligible HbA1c. - Conditions for verification: Link the other endpoints in the original record to the reason for exclusion from direct HbA1c evidence. - Why this condition is needed: Needed to avoid substituting changes in other metabolic markers for the selected endpoint. - Application exceptions: Do not establish an endpoint match solely from the 28-day randomized placebo design. - Remaining uncertainty: The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S04 ### N21 · What were the exposure and off-treatment periods in Devi/Ranjani? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S11 allocated 60 participants, 30 per arm, with metformin 500 mg/day for 6 weeks as common treatment and biotin 5 mg 2 times daily for 4 weeks followed by 2 weeks off. The verified weekly endpoints are FPG/PPG. - Why unverified: This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect. - Reason for missing information: This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect. - Required materials and conditions: Biotin 5 mg 2 times daily for 4 weeks; 2 weeks off; metformin 500 mg/day for 6 weeks in both arms; actual endpoints - Materials to obtain first: Biotin 5 mg 2 times daily for 4 weeks; 2 weeks off; metformin 500 mg/day for 6 weeks in both arms; actual endpoints - Further research: Verify administration, discontinuation and the presence of HbA1c at each time point in the original plan/results. - Conditions for verification: Link the retained exposure, common treatment and off-treatment period to the verified endpoints. - Why this condition is needed: Needed to preserve this candidate added-ingredient comparison without confusing duration and endpoints. - Application exceptions: Do not recast 4 weeks of use as 6 weeks of continuous exposure or HbA1c follow-up. - Remaining uncertainty: This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are internally designed - Related sources: S11 ### N22 · Were the completer analyses by arm and the flowchart’s 60 participants both retained? Verification status: Conflicting information Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S11’s results text/tables present completer analyses of control 28/biotin 26 participants, while the flowchart shows 60 completers. KO preserves both and explicitly states that Hb was not read as HbA1c. - Why unverified: Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either. - Reason for missing information: Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either. - Required materials and conditions: S11 results text/tables: control 28 and biotin 26 participants; flowchart: 60 completers; analysis definitions - Materials to obtain first: S11 results text/tables: control 28 and biotin 26 participants; flowchart: 60 completers; analysis definitions - Further research: Compare the original text, flowchart, corrections and analysis specifications to verify the reason for the denominator discrepancy. - Conditions for verification: Preserve conflicting denominators within the same report and the limits on attributing results/endpoints. - Why this condition is needed: Needed to avoid arbitrarily reconciling the conflicting completion/analysis denominators into the selected HbA1c sample. - Application exceptions: Do not read blood-test Hb as HbA1c. Recalculations of the original numbers/changes to the flowchart: 0. - Remaining uncertainty: Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S11 ### N23 · Are week 4 P=.001 and week 6 P=.087 the same result? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: In the same S11, the week 4 FPG endpoint comparison has nominal P=.001, and week 6 after discontinuation has P=.087. These are FPG results at different time points, not HbA1c. - Why unverified: Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed. - Reason for missing information: Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed. - Required materials and conditions: S11 FPG endpoint comparison: time point, whether biotin had been stopped, P, and whether the endpoint was HbA1c - Materials to obtain first: S11 FPG endpoint comparison: time point, whether biotin had been stopped, P, and whether the endpoint was HbA1c - Further research: Separately verify the prespecified plan, between-group estimates/intervals at each time point and the effect of discontinuation. - Conditions for verification: Retain the differences in results and exposure at the two time points together with the limits on direct attribution. - Why this condition is needed: Needed to avoid selecting only the positive time point or treating nonsignificance as equivalence. - Application exceptions: Do not transfer FPG results at different time points to an HbA1c effect or turn nonsignificance into an effect of 0. - Remaining uncertainty: Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M15 §15.3.1–15.3.3; internal application; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are internally designed - Related sources: S11 ### N24 · Were 447 participants and P=.03 used as a biotin-only HbA1c result? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: Albarracin S05 reports 447 participants, a combination of chromium 600 µg+biotin 2 mg/day for 90 days versus placebo, and a between-group HbA1c-change P=.03. The positive finding is preserved and is not attributed to biotin alone. - Why unverified: The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result. - Reason for missing information: The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result. - Required materials and conditions: S05: chromium 600 µg+biotin 2 mg/day for 90 days versus placebo; 447 participants; between-group HbA1c P=.03 - Materials to obtain first: S05: chromium 600 µg+biotin 2 mg/day for 90 days versus placebo; 447 participants; between-group HbA1c P=.03 - Further research: Separately verify an eligible HbA1c comparison in which only biotin differs against the same chromium background. - Conditions for verification: Link the combination-product results to the reason for exclusion from sole-biotin evidence. - Why this condition is needed: The positive HbA1c result must be preserved while limiting attribution because another ingredient also changed. - Application exceptions: The same background diabetes treatment does not isolate the incremental effects of chromium/biotin individually. - Remaining uncertainty: The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S05 ### N25 · Were 348 participants and the active arm’s 226 participants counted as a different study/the total n? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The related combination report’s 348 participants comprise active 226 and placebo 122 participants; 226 is not used as the total n. F04 conservatively groups possible overlap, and the S12 review is not added to its included studies. - Why unverified: The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0. - Reason for missing information: The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0. - Required materials and conditions: S05/S08/S13 and review S12: study families; 348=active 226/placebo 122; overlap relationships - Materials to obtain first: S05/S08/S13 and review S12: study families; 348=active 226/placebo 122; overlap relationships - Further research: Compare recruitment, periods and participant links across the relevant reports and registries. - Conditions for verification: Distinguish verified families/unconfirmed overlaps and report-specific denominators. - Why this condition is needed: Needed to avoid double-counting original reports, follow-up reports, registries and reviews as replication trials or participants. - Application exceptions: Do not convert a possibly shared cohort into either confirmed independence or confirmed complete identity. - Remaining uncertainty: The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S05, S08, S12, S13 ### N26 · Were Singer/Geohas’s sample and results verified? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S09 is primary_index_only for a chromium-biotin combination pilot report. F05’s S14 registry linkage is provisional, and the exact study-to-report link is unconfirmed. - Why unverified: The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0. - Reason for missing information: The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0. - Required materials and conditions: S09 original text and results tables; actual study linkage to registry S14; sole/combination composition - Materials to obtain first: S09 original text and results tables; actual study linkage to registry S14; sole/combination composition - Further research: Compare the S09 original text with the S14 history and actual recruitment/results. - Conditions for verification: Identify the verified title/index and the unverified original results/registry linkage. - Why this condition is needed: Needed to distinguish bibliographic discovery from verification of eligible results. - Application exceptions: Do not establish a confirmed shared family or participant count when the registry-number linkage is provisional. - Remaining uncertainty: The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: S09, S14 ### N27 · Were type 1 HbA1c candidates transferred to T2D? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F06/S10 is a biotin add-on-to-insulin study in type 1 diabetes and is not directly attributed to the adult T2D question. The historical PMC full access challenge/partial abstract level is preserved separately. - Why unverified: The PMC full text was not read this time, and results in the other population were not deleted. - Reason for missing information: The PMC full text was not read this time, and results in the other population were not deleted. - Required materials and conditions: S10’s actual type1 population, common insulin treatment and extraction level - Materials to obtain first: S10’s actual type1 population, common insulin treatment and extraction level - Further research: Verify direct T2D results separately and retain type1 data for a different question. - Conditions for verification: Link S10’s actual population mismatch to the historical access limitations. - Why this condition is needed: Needed to avoid counting human studies in a population different from the question’s population as direct results. - Application exceptions: Do not delete data from other populations or use them as evidence that no human studies exist. - Remaining uncertainty: The PMC full text was not read this time, and results in the other population were not deleted. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S10 ### N28 · Was GUTERRING excluded solely because its title mentions a combination? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F08/S15 is a biotin-only arm candidate in an officially indexed pilot open-label randomized 4-arm design. KO records that it was not excluded solely because of the combination wording in the title, but direct T2D HbA1c results remain unverified. - Why unverified: An indexed excerpt/shell does not constitute obtaining the complete registry plan/results. - Reason for missing information: An indexed excerpt/shell does not constitute obtaining the complete registry plan/results. - Required materials and conditions: NCT05832190’s actual 4 arms, biotin-only arm, population/follow-up HbA1c results and plan - Materials to obtain first: NCT05832190’s actual 4 arms, biotin-only arm, population/follow-up HbA1c results and plan - Further research: Verify the registry body/history, population, actual biotin-only arm results and HbA1c time points. - Conditions for verification: Indicate separately the retention of the registry candidate and the lack of verified direct results. - Why this condition is needed: Needed to avoid omitting a potential biotin-only arm candidate solely on the basis of the title. - Application exceptions: Do not claim that an eligible T2D HbA1c result has been verified solely because a biotin-only arm exists. - Remaining uncertainty: An indexed excerpt/shell does not constitute obtaining the complete registry plan/results. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application - Related sources: S15 ### N29 · Is a review counted as an original trial or independent verification? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: S12 is a 2022 systematic review/meta-analysis serving as a literature map; the retained location is the HbA1c subsection/refs32–39. KO did not double-count the review, original papers, follow-up reports and registries. - Why unverified: What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read. - Reason for missing information: What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read. - Required materials and conditions: The S12 review’s question, search cutoff, included studies/endpoints and links to original reports - Materials to obtain first: The S12 review’s question, search cutoff, included studies/endpoints and links to original reports - Further research: Compare the review’s inclusion tables with the original reports’ results and the overlap/sole-ingredient boundaries. - Conditions for verification: Distinguish the review’s role and the family/endpoint differences among its included original studies. - Why this condition is needed: Needed to avoid counting mixtures of endpoints/ingredients and repeated citations as independent results. - Application exceptions: Do not claim to have read the entire review/numeric files this time. - Remaining uncertainty: What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S01, S02, S04, S05, S08, S09, S11, S12, S13 ### N30 · Do the discovery and access failure concerning Coggeshall constitute a negative result? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: F09/S16 is at the level of bibliographic discovery of a 1985 report. The population/eligible original between-group HbA1c results were not sufficiently verified, and the historical access_level is metadata_and_failed_full_text. - Why unverified: The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result. - Reason for missing information: The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result. - Required materials and conditions: S16’s actual original text, population, sole-biotin comparison, HbA1c follow-up and historical failure record - Materials to obtain first: S16’s actual original text, population, sole-biotin comparison, HbA1c follow-up and historical failure record - Further research: Verify the relevant original text, population and follow-up results during an authorized update. - Conditions for verification: Separate the retained discovery/historical failure from the current unread status and the lack of verified eligible evidence. - Why this condition is needed: Needed to distinguish a candidate whose original text was not obtained from no effect. - Application exceptions: Do not use metadata_and_failed_full_text to represent a current failed-access action or worldwide study absence. - Remaining uncertainty: The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result. - Referenced methods: M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: S16 ### N31 · Is the lack of verified direct evidence expressed as 0 studies worldwide? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The original KO/assessment limits its statement to not having verified directly eligible results within the documented search scope. S17 WHO ICTRP was internal error/access_failed at the time; current external lookups/searches: 0. - Why unverified: Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date. - Reason for missing information: Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date. - Required materials and conditions: The 2026-09-15 original review/search scope, ICTRP failure and scope of this reading of retained material - Materials to obtain first: The 2026-09-15 original review/search scope, ICTRP failure and scope of this reading of retained material - Further research: Verify search records, unpublished studies/registries and correction coverage in an authorized update as a separate event. - Conditions for verification: Link every expression of absence or lack of verification to its actual scope and date. - Why this condition is needed: Needed to distinguish a bounded gate from complete absence of literature. - Application exceptions: The 0 searches this time do not mean 0 studies. Historical selection_log/ZIP references do not constitute current acquisition. - Remaining uncertainty: Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date. - Referenced methods: M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: S13, S14, S15, S16, S17 ### N32 · Was TSH/troponin interference generalized to interference with HbA1c itself? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The retained NIH/FDA content concerns selected thyroid tests after a single 10 mg dose within 24 hours, selected TSH/NT-proBNP tests in 6 people receiving 10 mg/day for 1 week, and falsely low results in some troponin tests. It does not establish the same interference in every test/HbA1c method. - Why unverified: Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules. - Reason for missing information: Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules. - Required materials and conditions: NIH/FDA’s specific assays, populations, exposures and time points, with separate verification of the HbA1c assay - Materials to obtain first: NIH/FDA’s specific assays, populations, exposures and time points, with separate verification of the HbA1c assay - Further research: Separately verify validation for each relevant HbA1c method and data on biotin exposure/blood-sampling time points. - Conditions for verification: Separate the assay/exposure scope of the retained safety material from the lack of verification for the selected HbA1c endpoint. - Why this condition is needed: Needed to avoid turning biotin interference into actual glycemic improvement or a risk for every test. - Application exceptions: Statements concerning specific TSH/NT-proBNP/troponin tests do not directly establish interference with an HbA1c assay. - Remaining uncertainty: Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.2 design-specific harm questions; temporal-relationship details are internally designed; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied - Related sources: S06, S07 ### N33 · Are the frequencies of nausea, loose stools and gastric irritation in S11 known? Verification status: Partly verified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: KO preserves nausea, loose stools and gastric irritation from the trial with common metformin treatment and states that the safety-analysis denominator is unclear. The stored summary read this time retains a reference to numeric_evidence N12 instead of specific event counts. - Why unverified: The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy. - Reason for missing information: The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy. - Required materials and conditions: People with AE/events by arm; collection; exposure/follow-up; safety-analysis denominators; discontinuation - Materials to obtain first: People with AE/events by arm; collection; exposure/follow-up; safety-analysis denominators; discontinuation - Further research: Separately verify the original AE tables, collection methods and arm-specific denominators/discontinuations. - Conditions for verification: Link the retained symptoms to gaps in safety denominators/directly eligible exposure. - Why this condition is needed: Needed to distinguish the presence of symptoms from incidence rates or a guarantee of long-term safety. - Application exceptions: Do not calculate event rates or NNH from unclear safety denominators, or treat unreported data as 0. - Remaining uncertainty: The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied - Related sources: S11 ### N34 · Is there safety evidence for long-term use, pregnancy/lactation, children, hepatic/renal disease and concurrent use? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The original safety_detail explicitly states that long-term add-on use in T2D, pregnancy, lactation, children, hepatic/renal disease, concurrent use and eligible dose-specific AE/discontinuations are unverified. - Why unverified: Unverified information does not establish either safety or harm, and no personal dosing instructions are created. - Reason for missing information: Unverified information does not establish either safety or harm, and no personal dosing instructions are created. - Required materials and conditions: Long-term AE and discontinuations by eligible dose; population-specific exposure/interactions and denominators - Materials to obtain first: Long-term AE and discontinuations by eligible dose; population-specific exposure/interactions and denominators - Further research: Separately verify long-term/population-specific harms and observation conditions for the same product and dose. - Conditions for verification: Distinguish direct information in the same population/exposure from unverified extensions. - Why this condition is needed: Needed to avoid guaranteeing safety in all populations from some brief observations. - Application exceptions: Do not unconditionally require every rare-harm study for the current narrow HbA1c question. - Remaining uncertainty: Unverified information does not establish either safety or harm, and no personal dosing instructions are created. - Referenced methods: M19 §19.1.2–19.2.4; internal application; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied - Related sources: S06, S07, S11 ### N35 · Is the actual scope of funding, product provision and COI known? Verification status: Unverified Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The funding fields of the 9 evidence items refer to trial_families.json for detailed verified and unverified information. The S11 location includes p106 COI, but the currently retained summary does not reproduce the specific disclosures. - Why unverified: The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement. - Reason for missing information: The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement. - Required materials and conditions: Report-specific funding, product provision, author relationships, COI declarations and original verification locations - Materials to obtain first: Report-specific funding, product provision, author relationships, COI declarations and original verification locations - Further research: Verify original research funding/COI and product supply records by report. - Conditions for verification: Distinguish the level of disclosures/funding actually verified from materials not read in this review. - Why this condition is needed: Required to avoid treating unverified funding as absent or as certification of independence. - Application exceptions: Do not automatically exclude a study or judge it free of bias solely on historical wording stating the presence or absence of COI. - Remaining uncertainty: The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement. - Referenced methods: Chamgap’s own independence and attribution criteria. The official methodological sections used in this pilot do not warrant all these detailed items; the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application. - Related sources: S01, S02, S04, S05, S08, S09, S10, S11, S15, S16 ### N36 · Have historical full-text access and current summary reading been separated? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: What was actually read in this review consists of the exact retained Korean content, bibliography and structure/metadata, with the retained summaries’ locations/values/SHA. publisher_full_pdf, author_text, official_extract, shell and failure are historical records; external materials/referenced historical ZIP files have not been read in this review. - Why unverified: Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition. - Reason for missing information: Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition. - Required materials and conditions: Historical access_level/location by report; actual access dates; current local locations/values/SHA; external access unattempted - Materials to obtain first: Historical access_level/location by report; actual access dates; current local locations/values/SHA; external access unattempted - Further research: If new access is separately authorized, independently record the material/time/original bytes. - Conditions for verification: Link reading badges to the actual retained citations and keep unread external materials separate. - Why this condition is needed: Required to avoid retroactively treating retained statements of PDF access as full-text reading in this review. - Application exceptions: If a report has no date field, leave it null; the global verified_date is a separate review date. - Remaining uncertainty: Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition. - Referenced methods: M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: S01, S02, S03, S04, S05, S06, S07, S08, S09, S10, S11, S12, S13, S14, S15, S16, S17 ### N37 · Have ?/null values and no_human_study=true been preserved unchanged? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: Preserve the original ?, null score, B/S, nulls on the subsequent 5 axes, no_human_study=true and human_study_exists=false unchanged. The assessment’s scope is direct eligible HbA1c results, and related_human_studies_exist=true. - Why unverified: Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict. - Reason for missing information: Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict. - Required materials and conditions: Original ?/null score; B/S; nulls on the subsequent 5 axes; bounded human scope; related studies true - Materials to obtain first: Original ?/null score; B/S; nulls on the subsequent 5 axes; bounded human scope; related studies true - Further research: If direct evidence is added, consider a separate update that preserves the original values/reasons for change. - Conditions for verification: Separate the scope expressed by the original verdict/gate from the statuses of the new criteria. - Why this condition is needed: Required to avoid treating the historical calculator gate as absence of all human studies or as a new efficacy grade. - Application exceptions: Do not alter the original false/true/null values for convenience or convert them to a score of 0 or a new criterion-fulfillment rate. - Remaining uncertainty: Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict. - Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.5, §4.6.3; the limits of the current data conversion follow the user’s scope and internal design; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: ### N38 · Have server_deployed and actual deployment in this work been distinguished? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: Preserve the original server_deployed=true, server_write_performed=false, deployed_at 2026-09-15 and initial snapshot scope. This work is a local table conversion, with 0 public site deployments. - Why unverified: Do not certify the current actual publication status solely from the original metadata. - Reason for missing information: Do not certify the current actual publication status solely from the original metadata. - Required materials and conditions: Original server_deployed/server_write_performed/first_published_scope; current local preparation - Materials to obtain first: Original server_deployed/server_write_performed/first_published_scope; current local preparation - Further research: If actual publication is separately authorized, verify the production URL/display/links and record the event. - Conditions for verification: Separate the original metadata values/scope from the current local conversion and absence of public deployment. - Why this condition is needed: Required to avoid treating historical deployment metadata as evidence of site publication in this work. - Application exceptions: Do not arbitrarily reconcile the original server_deployed=true and server_write=false. - Remaining uncertainty: Do not certify the current actual publication status solely from the original metadata. - Referenced methods: M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design - Related sources: ### N39 · Does the HbA1c table also answer questions about clinical events and improvements in quality of life? Verification status: Not applicable Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The selected question concerns between-group numerical HbA1c results. The original assessment uses an S surrogate and does not upgrade it to an H clinical event/P functional endpoint. - Why unverified: The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits. - Reason for missing information: The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits. - Required materials and conditions: Boundary between the selected HbA1c question and separate questions about complications, quality of life, mortality, duration/dose - Materials to obtain first: Boundary between the selected HbA1c question and separate questions about complications, quality of life, mortality, duration/dose - Further research: Review direct results and criteria separately for questions about events/long-term outcomes/dose. - Conditions for verification: Separate the directly selected endpoint from additional questions extending beyond it. - Why this condition is needed: Required to avoid extending a numerical surrogate outcome to benefits in clinical events. - Application exceptions: Do not make clinical-event trials an unconditional requirement for the numerical HbA1c question. - Remaining uncertainty: The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adapting outcomes to each question is internally designed; M03 §3.2.1–3.2.4; details concerning dose, duration and effect modification are internally designed; M03 §3.2.4; internal boundaries for extensions - Related sources: ### N40 · What changes when new direct results, full texts or corrections are acquired? Verification status: Met Reading scope: Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review - Current findings: The original revision_triggers are new direct HbA1c results, full texts/registrations/SAPs, corrections/retractions, numerical/classification errors and new safety materials. Maintain the same ID/URL and the policy of retaining old/new/reason/source/date. - Why unverified: No new search, calculation, update to the original verdict or public release was performed in this work. - Reason for missing information: No new search, calculation, update to the original verdict or public release was performed in this work. - Required materials and conditions: Original identity/dates; original values before/after; corrections/retractions; criterion versions; update links - Materials to obtain first: Original identity/dates; original values before/after; corrections/retractions; criterion versions; update links - Further research: Register separately authorized full texts, direct HbA1c results and corrections with their exact locations/values/hashes, then review the linked items again. - Conditions for verification: Explicitly link update triggers, required materials and affected items/preservation of history. - Why this condition is needed: Required to avoid making the current table a fixed truth or an automatic efficacy upgrade. - Application exceptions: Adding new materials is separate from amending criteria/reaching a new verdict and from deployment; do not exceed the current authorized scope. - Remaining uncertainty: No new search, calculation, update to the original verdict or public release was performed in this work. - Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M04 §4.5, §4.6.3; the limits of the current data conversion follow the user’s scope and internal design - Related sources: ## Evidence and sources ### S01 Maebashi et al. 1993. Therapeutic Evaluation of the Effect of Biotin on Hyperglycemia in Patients with Non-Insulin Dependent Diabetes Mellitus [Source](https://www.jstage.jst.go.jp/article/jcbn1986/14/3/14_3_211/_pdf) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: S01 fasting-glucose/blood-biotin data; direct between-group HbA1c result unverified Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: J Clin Biochem Nutr 14:211–218; Methods pp212–213; results p214; whole-paper endpoint inspection. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Publisher PDF link | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: J Clin Biochem Nutr 14:211–218; Methods pp212–213; results p214; whole-paper endpoint inspection. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S02 Báez-Saldaña et al. 2004. Effects of biotin on carboxylases and markers for glucose and lipid homeostasis [Source](https://www.researchgate.net/publication/7754969_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: S02 baseline glycated hemoglobin and enzyme/metabolic markers; follow-up between-group HbA1c result unverified Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: author_uploaded_full_text. Historically recorded location: Am J Clin Nutr 79:238–243; p239 procedures; Table2 p241; discussion p242; baseline characteristics. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Author-shared full-text page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: author_uploaded_full_text. Historically recorded location: Am J Clin Nutr 79:238–243; p239 procedures; Table2 p241; discussion p242; baseline characteristics. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S03 Báez-Saldaña et al. 2007. Erratum to 2004 biotin study [Source](https://www.researchgate.net/publication/297184582_Erratum_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects_Am) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Preserve location-specific 6.14→61.4 µmol/day and 20.5 µmol/day at other specified locations; new conversions: 0 Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: author_uploaded_correction_text. Historically recorded location: Am J Clin Nutr 85:570; correction paragraph. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Author-shared correction page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: author_uploaded_correction_text. Historically recorded location: Am J Clin Nutr 85:570; correction paragraph. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S04 Revilla-Monsalve et al. 2006. Biotin supplementation reduces plasma triacylglycerol and VLDL [Source](https://pubmed.ncbi.nlm.nih.gov/16677798/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Lipids, FPG and insulin; eligible between-group HbA1c result unverified Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_and_author_text. Historically recorded location: Biomed Pharmacother 60:182–185; abstract; Methods subjects/treatment and outcome table. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | PubMed bibliographic record and abstract | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. S04’s historical access to the author’s text does not mean current full-text reading at this PubMed URL. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_and_author_text. Historically recorded location: Biomed Pharmacother 60:182–185; abstract; Methods subjects/treatment and outcome table. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S05 Albarracin et al. 2008. Chromium picolinate and biotin combination improves glucose metabolism [Source](https://pubmed.ncbi.nlm.nih.gov/17506119/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: 447 participants, 90 days; chromium 600µg+biotin 2mg/P=.03; not attributable to biotin alone Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: pubmed_primary_abstract. Historically recorded location: Diabetes Metab Res Rev 24:41–51; abstract Methods/Results. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | PubMed bibliographic record and abstract | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: pubmed_primary_abstract. Historically recorded location: Diabetes Metab Res Rev 24:41–51; abstract Methods/Results. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S06 NIH Office of Dietary Supplements: Biotin—Health Professional Fact Sheet [Source](https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Biotin interference under specific assay and exposure conditions; does not demonstrate interference with HbA1c itself or all tests Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Official NIH ODS web document | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S07 FDA: Biotin Interference with Troponin Lab Tests—Assays Subject to Biotin Interference [Source](https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Falsely low results in some troponin assays; not direct evidence of actual HbA1c efficacy/risk rates Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Opening safety statement and paragraphs on residual assay interference. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Official FDA web document | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Opening safety statement and paragraphs on residual assay interference. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S08 Albarracin et al. 2007. Chromium and biotin: coronary risk factors in type 2 diabetes [Source](https://pubmed.ncbi.nlm.nih.gov/17684468/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: 348 participants, active 226/placebo 122; possible shared cohorts conservatively grouped/independent summations: 0 Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_mirror. Historically recorded location: J Cardiometab Syndr 2:91–97; abstract N=348, active226/placebo122. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | PubMed bibliographic record and abstract | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_mirror. Historically recorded location: J Cardiometab Syndr 2:91–97; abstract N=348, active226/placebo122. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S09 Singer and Geohas 2006. Chromium picolinate and biotin supplementation in poorly controlled type 2 diabetes [Source](https://pubmed.ncbi.nlm.nih.gov/17109595/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Original outcome extraction not acquired; S14 linkage provisional; not direct data on HbA1c from biotin alone Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_index_only. Historically recorded location: Title and bibliographic record; full outcome extraction not obtained. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | PubMed bibliographic record and abstract | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_index_only. Historically recorded location: Title and bibliographic record; full outcome extraction not obtained. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S10 Hemmati et al. 2013. Survey of biotin, glycemic control and plasma lipids in type 1 diabetes [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC3679599/) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Type 1 insulin add-on data; excluded from the direct T2D question/historical partial PMC access Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_index_partial. Historically recorded location: Title/abstract population; full PMC access challenge. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | PMC full-text page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_index_partial. Historically recorded location: Title/abstract population; full PMC access challenge. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S11 Devi and Ranjani 2016. Biotin added to metformin versus metformin alone in newly diagnosed type 2 diabetes [Source](https://www.iosrjournals.org/iosr-jdms/papers/Vol15-Issue%207/Version-9/R1507910106.pdf) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Common metformin allowed; HbA1c unverified; completers 28/26 versus flowchart 60; FPG P values at 4/6 weeks preserved Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: IOSR-JDMS 15(7)IX:100–106; p101 methods/flowchart; p102 completers/Table4; p104 Tables6–7; p105 Tables8–9; p106 COI. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Publisher PDF link | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: IOSR-JDMS 15(7)IX:100–106; p101 methods/flowchart; p102 completers/Table4; p104 Tables6–7; p105 Tables8–9; p106 COI. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S12 Zhang et al. 2022. Biotin interventions in type 2 diabetes: systematic review and meta-analysis [Source](https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1046800/full) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Included studies, combinations/sole ingredients and endpoints must be distinguished; duplicate summations as independent trials: 0 Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_text. Historically recorded location: Methods/search cutoff; HbA1c subsection; references32–39. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Publisher’s review full-text page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_text. Historically recorded location: Methods/search cutoff; HbA1c subsection; references32–39. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S13 ClinicalTrials.gov NCT00289354 [Source](https://clinicaltrials.gov/study/NCT00289354) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Registry URL/shell for the combination family; not upgraded to verification of the body text or plan Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL verified, rendered body not available. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | ClinicalTrials.gov registry page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL verified, rendered body not available. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S14 ClinicalTrials.gov NCT00308451 [Source](https://clinicaltrials.gov/study/NCT00308451) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Shell only; exact report linkage unconfirmed; not counted as a new independent study Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL accessed; exact study-to-report link not established. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | ClinicalTrials.gov registry page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL accessed; exact study-to-report link not established. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S15 ClinicalTrials.gov NCT05832190: GUTERRING [Source](https://clinicaltrials.gov/study/NCT05832190) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: 4-arm/biotin-only-arm candidate retained; eligible T2D HbA1c results/body text unverified Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_search_excerpt_and_shell. Historically recorded location: Official indexed title/design excerpt; direct body unavailable. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | ClinicalTrials.gov registry page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_search_excerpt_and_shell. Historically recorded location: Official indexed title/design excerpt; direct body unavailable. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S16 Coggeshall et al. 1985. Biotin Status and Plasma Glucose in Diabetics [Source](https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1985.tb18454.x) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: 1985 full text/eligible population/between-group HbA1c details unverified; the failure at the time was not a negative result Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: metadata_and_failed_full_text. Historically recorded location: Ann NY Acad Sci 447:389–392; article identified, outcome detail inaccessible. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | Publisher’s article page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: metadata_and_failed_full_text. Historically recorded location: Ann NY Acad Sci 447:389–392; article identified, outcome detail inaccessible. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ### S17 WHO ICTRP portal search for biotin [Source](https://trialsearch.who.int/?query=biotin) Materials actually read: The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review. Findings recorded in the summary: Historical internal error/access_failed; not an outcome or evidence of 0 studies worldwide Record level: Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review. Independent replication: 17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained archived summary: bibliography, linked summary/historical access | Retained locally | Acquired | Summary read | Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: access_failed. Historically recorded location: Search endpoint attempted, returned internal error. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | | WHO ICTRP search page | Unverified (0 external lookups in this review) | Access not attempted | Not read | Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: access_failed. Historically recorded location: Search endpoint attempted, returned internal error. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention. · Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported. · Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting. · Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence. · Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work ## What the statuses mean - Partly verified: Some related materials/identity/historical information are available, but gaps remain in direct comparisons, plans, access and harms - Unverified: The actual materials required for the selected direct comparison could not be verified within the retained scope; this does not mean no effect or 0 studies - Review incomplete: Comparison against original sources/search was not performed within the authorized scope - Not reported: A scoped status indicating that the item is not stated in the specific material/section that was read - Inaccessible: Used only for materials for which access was actually attempted and failed. Not assigned to the clinical materials in this work - Insufficient evidence for this criterion: Used only when relevant studies within a defined scope have been reviewed and the evidence is insufficient to answer the criterion. Not applied to all items in this work - Not applicable: The extension requiring clinical events beyond HbA1c does not apply; not a substitute for Unverified - Conflicting information: The conflict between completer and flowchart denominators in the same report is preserved; no new calculation or correction - Met: Verification of the stated preservation/boundary, distinction and linkage criteria; not new direct HbA1c efficacy evidence, full-text reading or safety certification ## Change history 2026-11-03 · Public page/materials 1.0. Public-facing display and data were created from the existing 40 items. No new clinical search, change in verification status or scoring was performed.