# Insulin degludec × Severe hypoglycemia — direct maintenance-period evidence sheet

Verdict 2922 · Evidence Check

Stored-material review date: Not recorded  
Original evidence cut-off: 2026-08-26  
Review-criteria version: 1.0  
Public page/material preparation date: 2026-10-10

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: Type 2 diabetes with hypoglycemia risk; detailed eligibility, baseline characteristics and risk subgroups remain unread
- Ingredient, formulation and route: Historical crossover-trial exposure to insulin degludec; not a recommendation on selection or use
- Dose: Original detailed doses, titration and administration times remain unread; no individual regimen, injection or dose-adjustment instructions
- Comparator: Active insulin glargine U100 control; two-period crossover in the same patients; detailed shared concurrent treatment remains unread
- Measured outcome: Proportion of patients experiencing severe hypoglycemia during 16-week maintenance, difference/CI/P; distinguished from the overall-endpoint effect
- Duration: Each 32-week period: initial 16-week titration and 16-week maintenance primary analysis; other periods/long-term follow-up remain separate gaps
- Questions outside this scope: Transferring the overall symptomatic composite effect to severe-only, HbA1c or long-term outcomes; Mixing event rates, patient proportions, contributors, FAS and completers; Correcting the original rate difference −23.66 using simple arithmetic; Adding two periods, the same people or recurrent events as new independent observations; Recommendations on insulin, doses, titration, injections, treatment choice, coverage or costs

## Checklist items

### N01 · Are subclaim C/D, original notes and parent C50/axes distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Selected severe hypoglycemia subclaim D has a note of maintenance-period 1.6% versus 2.4%, P=.35. It is distinguished from parent C50, safety caution and the original overall symptomatic verdict.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Absent subclaim scores, status and axes are not filled with parent values. There is no new split, verdict, grade or independent certification.
- Reason for missing information: Absent subclaim scores, status and axes are not filled with parent values. There is no new split, verdict, grade or independent certification.
- Required materials and conditions: Separate preservation of the selected claim, grade, note, absent values and parent values
- Materials to obtain first: Absent subclaim scores, status and axes are not filled with parent values. There is no new split, verdict, grade or independent certification.
- Further research: Additional material is linked with each selected question and parent context distinguished.
- Conditions for verification: Separate preservation of the selected claim, grade, note, absent values and parent values
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N02 · What are the actual population and baseline characteristics of type 2 diabetes with hypoglycemia risk?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: SWITCH2 is an insulin comparison trial in type 2 diabetes with hypoglycemia risk.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Detailed risk eligibility, previous hypoglycemia, baseline medication, renal/age/comorbidity characteristics and group/sequence composition are absent from the summary. Results are not automatically extended to other populations.
- Reason for missing information: Detailed risk eligibility, previous hypoglycemia, baseline medication, renal/age/comorbidity characteristics and group/sequence composition are absent from the summary. Results are not automatically extended to other populations.
- Required materials and conditions: Eligibility, risk criteria, baseline insulin, concurrent drugs and denominators
- Materials to obtain first: Detailed risk eligibility, previous hypoglycemia, baseline medication, renal/age/comorbidity characteristics and group/sequence composition are absent from the summary. Results are not automatically extended to other populations.
- Further research: Acquire original eligibility, baseline characteristics, risk criteria, concurrent exposure and denominators.
- Conditions for verification: Eligibility, risk criteria, baseline insulin, concurrent drugs and denominators
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N03 · What is the direct comparison between degludec and glargine U100?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing citation compares insulin degludec with insulin glargine U100; each patient received both insulins sequentially.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. This is not changed to other concentrations, other insulins, treatment discontinuation or no-insulin comparison. Product, dose, shared concurrent treatment and treatment-change details remain unread; no selection or regimen instructions are given.
- Reason for missing information: This is not changed to other concentrations, other insulins, treatment discontinuation or no-insulin comparison. Product, dose, shared concurrent treatment and treatment-change details remain unread; no selection or regimen instructions are given.
- Required materials and conditions: Original drugs, formulations, active control, shared treatment and actual exposure
- Materials to obtain first: This is not changed to other concentrations, other insulins, treatment discontinuation or no-insulin comparison. Product, dose, shared concurrent treatment and treatment-change details remain unread; no selection or regimen instructions are given.
- Further research: Acquire original drugs, formulations, active control, concurrent treatment, changes and actual exposure.
- Conditions for verification: Original drugs, formulations, active control, shared treatment and actual exposure
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N04 · What are the sequence, same-person and analysis relationships in the two-period crossover?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original randomized double-blind two-period crossover design gives both treatments to the same people.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Two periods, treatment-specific analyses and two questions are not added as new people or independent trials. Original sequence counts, period/sequence models, treatment changes and censoring remain unread.
- Reason for missing information: Two periods, treatment-specific analyses and two questions are not added as new people or independent trials. Original sequence counts, period/sequence models, treatment changes and censoring remain unread.
- Required materials and conditions: Assigned sequences, each period, treatment-specific contributions, correlation and denominators
- Materials to obtain first: Two periods, treatment-specific analyses and two questions are not added as new people or independent trials. Original sequence counts, period/sequence models, treatment changes and censoring remain unread.
- Further research: Acquire original sequence allocation, period/treatment contributions, correlations, models and denominators.
- Conditions for verification: Assigned sequences, each period, treatment-specific contributions, correlation and denominators
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N05 · Are each 32-week period, 16-week titration and 16-week maintenance windows distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary says the initial 16 weeks of each 32-week period were for titration, with only maintenance used in primary analysis. The evidence entry concerns the 16-week maintenance endpoint.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Time in the two periods is not newly added, and titration/full-period values are not moved into maintenance results. No titration method, usage instruction or actual period/exposure is invented.
- Reason for missing information: Time in the two periods is not newly added, and titration/full-period values are not moved into maintenance results. No titration method, usage instruction or actual period/exposure is invented.
- Required materials and conditions: Original periods, titration, maintenance, primary window and actual exposure
- Materials to obtain first: Time in the two periods is not newly added, and titration/full-period values are not moved into maintenance results. No titration method, usage instruction or actual period/exposure is invented.
- Further research: Acquire original period-specific plans, actual exposure, observation windows, denominators and analyses.
- Conditions for verification: Original periods, titration, maintenance, primary window and actual exposure
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N06 · Are carryover-mitigation plans distinguished from gaps on residual effects?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary describes crossover’s reduction of between-person variation, possible carryover and a 16-week titration plan to reduce it. It records that crossover itself was not a listed defect.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. A titration plan alone does not newly certify zero carryover or complete resolution. Washout, period/sequence tests and sensitivity details remain unread.
- Reason for missing information: A titration plan alone does not newly certify zero carryover or complete resolution. Washout, period/sequence tests and sensitivity details remain unread.
- Required materials and conditions: Original titration plans, period effects, residual effects, sequence and sensitivity
- Materials to obtain first: A titration plan alone does not newly certify zero carryover or complete resolution. Washout, period/sequence tests and sensitivity details remain unread.
- Further research: Acquire original period/sequence, carryover, titration and sensitivity plans/results.
- Conditions for verification: Original titration plans, period effects, residual effects, sequence and sensitivity
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N07 · Are 721 randomized, 720 FAS, 580 completed and treatment-specific 632/618 distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing evidence list gives 721 randomized, 720 FAS and 580 completed. The original Korean article records treatment-specific primary contributors of 632 and 618.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. 632/618 are not newly mapped to treatment names absent from the existing summary or added as different people. FAS720, completed580 and primary contributors do not substitute for the same population.
- Reason for missing information: 632/618 are not newly mapped to treatment names absent from the existing summary or added as different people. FAS720, completed580 and primary contributors do not substitute for the same population.
- Required materials and conditions: Randomized, FAS, completers, contributors and each treatment/period denominator
- Materials to obtain first: 632/618 are not newly mapped to treatment names absent from the existing summary or added as different people. FAS720, completed580 and primary contributors do not substitute for the same population.
- Further research: Acquire original flow, treatment/period contributions, sequences, population definitions and denominators.
- Conditions for verification: Randomized, FAS, completers, contributors and each treatment/period denominator
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N08 · What are the limits of completed 80.4%, not completed 19.6% and original missing-data handling?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: 580/721 completed, 80.4%; not completed, 19.6%; and ITT/missingness-sensitivity analyses are retained as described in the original article.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. No new dropout rate, group missingness or imputed values are calculated. Original missing-data analysis wording does not certify resolution of all missingness bias or complete follow-up.
- Reason for missing information: No new dropout rate, group missingness or imputed values are calculated. Original missing-data analysis wording does not certify resolution of all missingness bias or complete follow-up.
- Required materials and conditions: Completion, discontinuation reasons, treatment/period missingness, models and sensitivity
- Materials to obtain first: No new dropout rate, group missingness or imputed values are calculated. Original missing-data analysis wording does not certify resolution of all missingness bias or complete follow-up.
- Further research: Acquire original discontinuation, missingness, imputation/sensitivity assumptions, populations, effects and intervals.
- Conditions for verification: Completion, discontinuation reasons, treatment/period missingness, models and sensitivity
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N09 · What is the overall symptomatic endpoint definition involving severe or glucose-confirmed events?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original primary endpoint is externally adjudicated severe events requiring third-party assistance, or events combining glucose <56mg/dL with symptoms.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. This is not changed to a lab value alone, all asymptomatic hypoglycemia or severe events alone. Recurrent-event distinctions, ascertainment schedules and collection details remain unread.
- Reason for missing information: This is not changed to a lab value alone, all asymptomatic hypoglycemia or severe events alone. Recurrent-event distinctions, ascertainment schedules and collection details remain unread.
- Required materials and conditions: Severe events, third-party assistance, external adjudication, glucose/symptoms and event ascertainment
- Materials to obtain first: This is not changed to a lab value alone, all asymptomatic hypoglycemia or severe events alone. Recurrent-event distinctions, ascertainment schedules and collection details remain unread.
- Further research: Acquire original definitions, external adjudication, combined symptoms/testing, people/recurrent events and periods.
- Conditions for verification: Severe events, third-party assistance, external adjudication, glucose/symptoms and event ascertainment
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N10 · What scales do 185.6/265.4 events, 0.70 and the 95% CI represent?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Overall symptomatic hypoglycemia during 16-week maintenance was 185.6 versus 265.4 events/100 patient-years; rate ratio 0.70 (95% CI 0.61–0.80).
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Event rates are not changed into patient proportions, risk ratios or total people. Recurrent events, patient-time, adjustment and detailed test P values are not invented.
- Reason for missing information: Event rates are not changed into patient proportions, risk ratios or total people. Recurrent events, patient-time, adjustment and detailed test P values are not invented.
- Required materials and conditions: Patient-time, event rates, original ratio, model, interval and denominator
- Materials to obtain first: Event rates are not changed into patient proportions, risk ratios or total people. Recurrent events, patient-time, adjustment and detailed test P values are not invented.
- Further research: Acquire original event/time tables, rate models, adjustment, group exposure, CIs and tests.
- Conditions for verification: Patient-time, event rates, original ratio, model, interval and denominator
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N11 · Was the original absolute rate difference −23.66 retained without recalculation as a simple difference?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary and evidence list separately record an absolute rate difference of −23.66 events/100 patient-years.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. 185.6/265.4 are not subtracted again to replace/correct this original value. Calculation model, adjustment, CI and P value are not filled in if unspecified.
- Reason for missing information: 185.6/265.4 are not subtracted again to replace/correct this original value. Calculation model, adjustment, CI and P value are not filled in if unspecified.
- Required materials and conditions: Original rate difference, model, scale, denominator and uncertainty
- Materials to obtain first: 185.6/265.4 are not subtracted again to replace/correct this original value. Calculation model, adjustment, CI and P value are not filled in if unspecified.
- Further research: Acquire original rate-difference calculation, model, denominator, period and interval.
- Conditions for verification: Original rate difference, model, scale, denominator and uncertainty
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N12 · Are affected-patient proportions 22.5%/31.6% and original −9.1%p distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Patients experiencing overall symptomatic events were 22.5% versus 31.6%; the original absolute difference was −9.1%p.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. This proportion is not converted to a recurrent-event rate, severe proportion or new patient count. No new NNT, difference CI, P value or absolute-event example is created.
- Reason for missing information: This proportion is not converted to a recurrent-event rate, severe proportion or new patient count. No new NNT, difference CI, P value or absolute-event example is created.
- Required materials and conditions: Affected patients, at least one event, denominator, period, difference and interval
- Materials to obtain first: This proportion is not converted to a recurrent-event rate, severe proportion or new patient count. No new NNT, difference CI, P value or absolute-event example is created.
- Further research: Acquire original affected-patient definitions, group denominators, event mapping, original difference/interval and tests.
- Conditions for verification: Affected patients, at least one event, denominator, period, difference and interval
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N13 · Are severe 1.6%/2.4%, −0.8%p, CI and P retained in their original scope?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Patients experiencing severe events during maintenance were 1.6% versus 2.4%; difference −0.8%p (95% CI −2.2–0.5; P=.35).
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. This value is not changed to events/patient-year, overall symptomatic effects or severe effects in other periods. No new people/event counts, rate ratios, CIs or P values are created.
- Reason for missing information: This value is not changed to events/patient-year, overall symptomatic effects or severe effects in other periods. No new people/event counts, rate ratios, CIs or P values are created.
- Required materials and conditions: Severe definition requiring third-party assistance, patient proportions, original denominators, difference, CI and P
- Materials to obtain first: This value is not changed to events/patient-year, overall symptomatic effects or severe effects in other periods. No new people/event counts, rate ratios, CIs or P values are created.
- Further research: Acquire original severe events, affected patients, denominators, periods, difference/interval and tests.
- Conditions for verification: Severe definition requiring third-party assistance, patient proportions, original denominators, difference, CI and P
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N14 · Are overall-endpoint improvement and severe-only uncertainty separated?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary says overall symptomatic outcomes improved but the severe maintenance-period difference was not significant. Subclaim C/D are distinguished.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Overall effects, average glucose or mechanisms do not establish severe reduction; P=.35 is not judged as an exact zero effect or equivalence.
- Reason for missing information: Overall effects, average glucose or mechanisms do not establish severe reduction; P=.35 is not judged as an exact zero effect or equivalence.
- Required materials and conditions: Overall/components, hierarchy, denominators, original effects, tests and interpretation
- Materials to obtain first: Overall effects, average glucose or mechanisms do not establish severe reduction; P=.35 is not judged as an exact zero effect or equivalence.
- Further research: Acquire original component-specific plans, effects, intervals, hierarchy and precision.
- Conditions for verification: Overall/components, hierarchy, denominators, original effects, tests and interpretation
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N15 · Are secondary HbA1c noninferiority and primary hypoglycemia separated?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary records HbA1c as a secondary efficacy endpoint, noninferior in both periods.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. HbA1c is not promoted to primary hypoglycemia; values, margins, CIs, P values or overall/severe effects absent from the existing summary are not filled in.
- Reason for missing information: HbA1c is not promoted to primary hypoglycemia; values, margins, CIs, P values or overall/severe effects absent from the existing summary are not filled in.
- Required materials and conditions: Original secondary efficacy, noninferiority plans, periods, denominators and margins
- Materials to obtain first: HbA1c is not promoted to primary hypoglycemia; values, margins, CIs, P values or overall/severe effects absent from the existing summary are not filled in.
- Further research: Separately acquire original HbA1c plans, margins, group values, denominators, periods and tests.
- Conditions for verification: Original secondary efficacy, noninferiority plans, periods, denominators and margins
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N16 · What are the gaps in direct precision and event ascertainment for severe-only reduction?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Original severe events required third-party assistance and external adjudication; affected patients during maintenance were 1.6%/2.4%, difference CI −2.2–0.5; P=.35.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Overall symptomatic rates or HbA1c do not fill direct severe effects. Severe patient counts, recurrence, exposure time, other-period effects and CIs are not invented.
- Reason for missing information: Overall symptomatic rates or HbA1c do not fill direct severe effects. Severe patient counts, recurrence, exposure time, other-period effects and CIs are not invented.
- Required materials and conditions: Severe definitions, external adjudication, patients/events, exposure, denominators and original effects
- Materials to obtain first: Overall symptomatic rates or HbA1c do not fill direct severe effects. Severe patient counts, recurrence, exposure time, other-period effects and CIs are not invented.
- Further research: Acquire original severe-event adjudication, people/event tables, group denominators, periods, models and plans.
- Conditions for verification: Severe definitions, external adjudication, patients/events, exposure, denominators and original effects
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N17 · What is actual access to primary/secondary hierarchy, multiplicity, registration and SAP?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original registration identifier is NCT02030600; the primary endpoint is the 16-week maintenance overall symptomatic hypoglycemia rate.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Registration, full text and plans were not newly read. Exact hierarchy, α, multiplicity, prespecified subgroups or changes for severe/other periods are not newly established.
- Reason for missing information: Registration, full text and plans were not newly read. Exact hierarchy, α, multiplicity, prespecified subgroups or changes for severe/other periods are not newly established.
- Required materials and conditions: Original registration, protocol, SAP, primary/secondary outcomes, changes and models
- Materials to obtain first: Registration, full text and plans were not newly read. Exact hierarchy, α, multiplicity, prespecified subgroups or changes for severe/other periods are not newly established.
- Further research: Acquire original registration, plans, hierarchy, multiplicity, models and changes.
- Conditions for verification: Original registration, protocol, SAP, primary/secondary outcomes, changes and models
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N18 · Are identical vials/syringes, double blinding and actual assessment distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary records double blinding, identical vials/syringes, ITT and missingness sensitivity as historical reasons for not counting additional defects.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. This does not certify new completed review or absence of all bias. Successful masking, allocation concealment and analyst/adjudicator details remain unread.
- Reason for missing information: This does not certify new completed review or absence of all bias. Successful masking, allocation concealment and analyst/adjudicator details remain unread.
- Required materials and conditions: Allocation, concealment, masking, identical tools, adjudication and analysis
- Materials to obtain first: This does not certify new completed review or absence of all bias. Successful masking, allocation concealment and analyst/adjudicator details remain unread.
- Further research: Acquire original allocation, masking, external adjudication, analysis and missingness.
- Conditions for verification: Allocation, concealment, masking, identical tools, adjudication and analysis
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N19 · Are Novo support, two employees and design/data/writing roles each preserved?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Novo Nordisk support, 2 employee authors and involvement in design, data and medical writing are preserved as in the existing summary.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Two employees are not certified as independent authors, and funding alone does not fill trial-drug provision or external-analysis roles. Parent I0 is also preserved.
- Reason for missing information: Two employees are not certified as independent authors, and funding alone does not fill trial-drug provision or external-analysis roles. Parent I0 is also preserved.
- Required materials and conditions: Funding, drugs/in-kind support, employees, external analysis and design/data/medical writing
- Materials to obtain first: Two employees are not certified as independent authors, and funding alone does not fill trial-drug provision or external-analysis roles. Parent I0 is also preserved.
- Further research: Separately acquire original cash, drug/in-kind support, affiliations and design/data/analysis/writing disclosures.
- Conditions for verification: Funding, drugs/in-kind support, employees, external analysis and design/data/medical writing
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N20 · Were one trial, two periods, recurrent events and two tables kept from independent addition?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: One Wysham2017 SWITCH2 report and the same crossover population share two existing questions.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Periods, treatment contributions, recurrent events and overall/severe components are not added as new trials/participants. Final independent counts and participant totals are null.
- Reason for missing information: Periods, treatment contributions, recurrent events and overall/severe components are not added as new trials/participants. Final independent counts and participant totals are null.
- Required materials and conditions: Bibliography, trial, same people, periods and sibling-question relationships
- Materials to obtain first: Periods, treatment contributions, recurrent events and overall/severe components are not added as new trials/participants. Final independent counts and participant totals are null.
- Further research: Link added reports to original registration, the same population, outcomes and period relationships.
- Conditions for verification: Bibliography, trial, same people, periods and sibling-question relationships
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N21 · Do gaps remain for nocturnal, other-period, baseline-risk-subgroup and individual effects?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: Core values in the designated existing summary concern overall symptomatic and severe outcomes during 16-week maintenance.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. No nocturnal, titration, full-period, baseline-risk-specific effect, individual suitability or drug choice is invented.
- Reason for missing information: No nocturnal, titration, full-period, baseline-risk-specific effect, individual suitability or drug choice is invented.
- Required materials and conditions: Original prespecified subgroups, timepoints, outcomes, interactions and denominators
- Materials to obtain first: No nocturnal, titration, full-period, baseline-risk-specific effect, individual suitability or drug choice is invented.
- Further research: Acquire original period/subgroup plans, outcomes, denominators, interactions and multiplicity.
- Conditions for verification: Original prespecified subgroups, timepoints, outcomes, interactions and denominators
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N22 · Are hypoglycemia outcomes separated from other drug harms and safety denominators?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The existing summary records patient-experienced hypoglycemia as a treatment harm. Both treatments are insulins and parent safety is caution.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Reduced overall hypoglycemia is not extended to absence of other harms or overall drug safety. Other-harm tables, relatedness and safety populations remain unread.
- Reason for missing information: Reduced overall hypoglycemia is not extended to absence of other harms or overall drug safety. Other-harm tables, relatedness and safety populations remain unread.
- Required materials and conditions: Harm definitions, people/events, actual exposure, denominators and relatedness
- Materials to obtain first: Reduced overall hypoglycemia is not extended to absence of other harms or overall drug safety. Other-harm tables, relatedness and safety populations remain unread.
- Further research: Acquire original other harms, group people/events, safety denominators, exposure and relatedness.
- Conditions for verification: Harm definitions, people/events, actual exposure, denominators and relatedness
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N23 · What are the gaps in rare/long-term harms, discontinuation, actual exposure and treatment application?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: Original completion/contribution limitations and the severe-proportion CI are preserved; long-term/rare-harm tables were not provided.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. No dose-adjustment, monitoring, injection, treatment choice/substitution, coverage or cost guidance is created. Nonreporting/nonsignificance is not used as long-term safety or zero rare events.
- Reason for missing information: No dose-adjustment, monitoring, injection, treatment choice/substitution, coverage or cost guidance is created. Nonreporting/nonsignificance is not used as long-term safety or zero rare events.
- Required materials and conditions: Original harm collection, exposure, discontinuation, follow-up, periods and independent relationships
- Materials to obtain first: No dose-adjustment, monitoring, injection, treatment choice/substitution, coverage or cost guidance is created. Nonreporting/nonsignificance is not used as long-term safety or zero rare events.
- Further research: Acquire original exposure, harm-related discontinuation, collection, rare/long-term outcomes and direct material for new populations/drugs.
- Conditions for verification: Original harm collection, exposure, discontinuation, follow-up, periods and independent relationships
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N24 · Are stored summaries, bibliographic URLs, registration identifiers and external access distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The complete stored parent-verdict summary was read for production; Wysham2017 PubMed PMID28672317, registration identifier NCT02030600 and the original source URL were linked.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. External abstracts, full texts, registration, protocols and SAPs remain unread. No new URL/DOI is constructed from identifiers and no separate link test was run.
- Reason for missing information: External abstracts, full texts, registration, protocols and SAPs remain unread. No new URL/DOI is constructed from identifiers and no separate link test was run.
- Required materials and conditions: Original bibliography, URLs, identifiers and access to abstracts/full texts/registration/plans
- Materials to obtain first: External abstracts, full texts, registration, protocols and SAPs remain unread. No new URL/DOI is constructed from identifiers and no separate link test was run.
- Further research: Link user-provided individual source material to its type and access status.
- Conditions for verification: Original bibliography, URLs, identifiers and access to abstracts/full texts/registration/plans
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

### N25 · Are Korean/English, axes, the reference date, corrections, empty values, candidate history and current production preserved?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: 2026-08-26, empty correction/deliberation values, parent C50, safety caution, axes, Korean/English articles, selected subclaim C/D and notes are preserved in their original form.
- Why unverified: Only relevant stored-summary information is recorded; detailed original material and user review remain outstanding. Original design/missingness and prescription/cost explanations are historical, not current review, lookup or recommendations. Absent subclaim values are not filled; candidate review-pending/production-eligible indicators are historical.
- Reason for missing information: Original design/missingness and prescription/cost explanations are historical, not current review, lookup or recommendations. Absent subclaim values are not filled; candidate review-pending/production-eligible indicators are historical.
- Required materials and conditions: Distinguishing the selected verdict record, complete parent, original languages, history and current production
- Materials to obtain first: Original design/missingness and prescription/cost explanations are historical, not current review, lookup or recommendations. Absent subclaim values are not filled; candidate review-pending/production-eligible indicators are historical.
- Further research: Only user-added material/decisions are linked as separate events after preserving the complete original.
- Conditions for verification: Distinguishing the selected verdict record, complete parent, original languages, history and current production
- Why this condition is needed: Individual production conditions recording original selected claims, comparisons, denominators, periods and interpretive limits
- Application exceptions: Unread external material, other questions or out-of-scope outcomes do not substitute for satisfied conditions, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Selected claim: Reduced severe hypoglycemia
- Related sources: R01

## Evidence and sources

### R01

Wysham C, Bhargava A, Chaykin L, et al. Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes. JAMA. 2017;318(1):45-56. PMID: 28672317.

[PubMed](https://pubmed.ncbi.nlm.nih.gov/28672317/)

Materials actually read: Summary read; external materials not read  
Findings recorded in the summary: 185.6 versus 265.4 events/100 patient-years; rate ratio 0.70 (0.61–0.80), absolute difference -23.66 events/100 patient-years; patient-proportion difference -9.1%p  
Record level: Stored review summary; not a result of comparing the original external report here  
Independent replication: Family IDs link relationships and do not certify unique trial counts; added reports, sibling questions, the same participants and outcomes are not added independently. F01: the same SWITCH2 crossover report, patients, two periods, recurrent events and overall/severe hypoglycemia are shared by both subquestions

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Stored existing review summary | Original URL preserved | Summary read | Summary read | Stored parent-verdict summary |
| External abstract | Original URL preserved | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review |
| External full paper | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review |
| External registration | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review |
| External protocol and SAP | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review |

## 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 conditions and reasons for changes, and distinguish variations in interventions. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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 studies from reports and link them; do not omit a study solely because results are unreported. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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 · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing

## What the statuses mean

- Partly verified: Some information is in the stored summary; detailed original material remains unverified. This does not certify passed review or clinical efficacy
- Unverified: Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety
- Review incomplete: Awaiting user review
- Met: Use only within the relevant condition's scope after user review; no automatic display in this preparation
- Not reported: Distinguish only within materials actually read; do not turn unread external materials into unreported findings
- Inaccessible: Not applied during this preparation because actual access was not tested
- Not applicable: Use with a reason for non-applicability based on an explicit question boundary
- Conflicting data: Judge after actual material comparison; review was not performed during this preparation
- Insufficient evidence for the conditions: Do not use as a clinical grade encompassing currently unread materials

## Change history

2026-10-10 · Public page/materials 1.0. The public page and data were prepared from the existing 25 items. No new clinical search, verification-status change or scoring was performed.