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Study · Observational study · 2022

9 results

Emulating the GRADE trial using real world data: retrospective comparative effectiveness study.

Deng Y, Polley EC, Wallach JD, Dhruva SS, Herrin J, Quinto K, Gandotra C, Crown W, Noseworthy P, Yao X, Lyon TD, Shah ND, Ross JS, McCoy RG

BMJ (Clinical research ed.)3 Oct 2022Cited by 24 (Europe PMC)

PMID36191949 (opens in a new tab)PMCIDPMC9527635 (opens in a new tab)DOI10.1136/bmj-2022-070717 (opens in a new tab)PepBankPUB-36191949
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Summary

ObjectiveTo emulate the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) trial using real world data before its publication. GRADE directly compared second line glucose lowering drugs for their ability to lower glycated hemoglobin A1c (HbA1c).DesignObservational study.SettingOptumLabs® Data Warehouse (OLDW), a nationwide claims database in the US, 25 January 2010 to 30 June 2019.ParticipantsAdults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.Main outcome measuresThe primary outcome was time to HbA1c ≥7.0%. Secondary outcomes were time to HbA1c >7.5%, incident microvascular complications, incident macrovascular complications, adverse events, all cause hospital admissions, and all cause mortality. Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.Results8252 people were identified (19.7% of adults starting the study drugs in OLDW) who met eligibility criteria for the GRADE trial (glimepiride arm=4318, liraglutide arm=690, sitagliptin arm=2993, glargine arm=251). The glargine arm was excluded from analyses owing to small sample size. Median times to HbA1c ≥7.0% were 442 days (95% confidence interval 394 to 480 days) for glimepiride, 764 (741 to not calculable) days for liraglutide, and 427 (380 to 483) days for sitagliptin. Liraglutide was associated with lower risk of reaching HbA1c ≥7.0% compared with glimepiride (hazard ratio 0.57, 95% confidence interval 0.43 to 0.75) and sitagliptin (0.55, 0.41 to 0.73). Results were consistent for the secondary outcome of time to HbA1c >7.5%. No significant differences were observed among treatment groups for the remaining secondary outcomes.ConclusionsIn this emulation of the GRADE trial, liraglutide was statistically significantly more effective at maintaining glycemic control than glimepiride or sitagliptin when added to metformin monotherapy. Generating timely evidence on medical treatments using real world data as a complement to prospective trials is of value.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

  1. 01HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, median time to HbA1c of 7.0% or higher was longer with liraglutide (764 days) than with glimepiride (442 days) or sitagliptin (427 days).

    In plain wordsIn adults with type 2 diabetes, blood sugar stayed in target longer with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    IncreaseMedian time to HbA1c of 7.0% or higher
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Median time to HbA1c >=7.0%
    764 days
    liraglutide
    Median time to HbA1c >=7.0%
    442 days
    glimepiride
    Median time to HbA1c >=7.0%
    427 days
    sitagliptin

    Source sentences

    Summary
    Median times to HbA1c ≥7.0% were 442 days (95% confidence interval 394 to 480 days) for glimepiride, 764 (741 to not calculable) days for liraglutide, and 427 (380 to 483) days for sitagliptin.
    2 context sentences
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  2. 02HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, liraglutide was linked to a lower risk of reaching HbA1c of 7.0% or higher than glimepiride (hazard ratio 0.57).

    In plain wordsIn adults with type 2 diabetes, liraglutide was linked to a lower chance of losing blood sugar control than glimepiride.

    Peptide
    Liraglutide
    Outcome
    DecreaseRisk of reaching HbA1c of 7.0% or higher versus glimepiride
    Study

    n: not reported in source

    Comparator
    Glimepiride
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio, time to HbA1c >=7.0%
    0.57 HR
    liraglutide vs glimepiride

    Source sentences

    Summary
    Liraglutide was associated with lower risk of reaching HbA1c ≥7.0% compared with glimepiride (hazard ratio 0.57, 95% confidence interval 0.43 to 0.75) and sitagliptin (0.55, 0.41 to 0.73).
    2 context sentences
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  3. 03HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, liraglutide was linked to a lower risk of reaching HbA1c of 7.0% or higher than sitagliptin (hazard ratio 0.55).

    In plain wordsIn adults with type 2 diabetes, liraglutide was linked to a lower chance of losing blood sugar control than sitagliptin.

    Peptide
    Liraglutide
    Outcome
    DecreaseRisk of reaching HbA1c of 7.0% or higher versus sitagliptin
    Study

    n: not reported in source

    Comparator
    Sitagliptin
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio, time to HbA1c >=7.0%
    0.55 HR
    liraglutide vs sitagliptin

    Source sentences

    Summary
    Liraglutide was associated with lower risk of reaching HbA1c ≥7.0% compared with glimepiride (hazard ratio 0.57, 95% confidence interval 0.43 to 0.75) and sitagliptin (0.55, 0.41 to 0.73).
    2 context sentences
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  4. 04HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, results for time to HbA1c above 7.5% were consistent with the primary outcome, favouring liraglutide over glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, liraglutide also kept blood sugar below a higher limit longer than glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    DecreaseTime to HbA1c above 7.5%
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Results were consistent for the secondary outcome of time to HbA1c >7.5%.
    2 context sentences
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  5. 05HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, incident microvascular complications did not differ significantly among liraglutide, glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, new small-vessel complications were not significantly different with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    No significant changeIncident microvascular complications
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Kidney function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant differences were observed among treatment groups for the remaining secondary outcomes.
    3 context sentences
    Summary · context
    incident microvascular complications, incident macrovascular complications
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  6. 06HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, incident macrovascular complications did not differ significantly among liraglutide, glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, new large-vessel complications were not significantly different with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    No significant changeIncident macrovascular complications
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant differences were observed among treatment groups for the remaining secondary outcomes.
    3 context sentences
    Summary · context
    incident microvascular complications, incident macrovascular complications
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  7. 07HumanObservational studySafety outcome

    In adults with type 2 diabetes on metformin, adverse events did not differ significantly among liraglutide, glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, side effects were not significantly different with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    No significant changeAdverse events
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant differences were observed among treatment groups for the remaining secondary outcomes.
    3 context sentences
    Summary · context
    adverse events, all cause hospital admissions, and all cause mortality.
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  8. 08HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, all cause hospital admissions did not differ significantly among liraglutide, glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, hospital stays were not significantly different with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    No significant changeAll cause hospital admissions
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant differences were observed among treatment groups for the remaining secondary outcomes.
    3 context sentences
    Summary · context
    all cause hospital admissions, and all cause mortality.
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.
  9. 09HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes on metformin, all cause mortality did not differ significantly among liraglutide, glimepiride and sitagliptin.

    In plain wordsIn adults with type 2 diabetes, deaths were not significantly different with liraglutide than with glimepiride or sitagliptin.

    Peptide
    Liraglutide
    Outcome
    No significant changeAll cause mortality
    Study

    n: not reported in source

    Comparator
    Glimepiride and sitagliptin
    Analysis
    Secondary
    Outcome group
    Mortality · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    No significant differences were observed among treatment groups for the remaining secondary outcomes.
    3 context sentences
    Summary · context
    all cause mortality.
    Summary · context
    Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine.
    Summary · context
    Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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