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Study · Systematic review · 2026

9 results

Efficacy and safety of orforglipron in type 2 diabetes mellitus and obesity: a GRADE-assessed meta-analysis and trial sequential analysis with subgroup evaluations by diabetic status, obesity status, and dose regimens.

Jamal A, Khan S, Qadri M, Shah A, Iftikhar H, Fatima E, Ahmad M, Sikandar M, Jawed I, Muneeb M, Mohmand MS, Bacha Z and 5 more

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Khan BW, Jamal T, Khalid AA, Khan MI, Zulkaif M

Acta diabetologica7 Jan 2026Cited by 1 (Europe PMC)

PMID41498807 (opens in a new tab)DOI10.1007/s00592-025-02635-8 (opens in a new tab)PepBankPUB-41498807
Publisher pagePubMedAsk about this study
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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study9

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

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron reduced HbA1c versus placebo in both the primary and sensitivity pooled analyses.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron lowered long-term blood sugar more than placebo in the main and the sensitivity pooled analyses.

    Peptide
    Orforglipron
    Outcome
    DecreaseHbA1c pooled effect
    Study

    n: not reported in source

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

    Measurements

    HbA1c mean difference
    −1.07%
    primary pooled analysis
    HbA1c mean difference
    −1.45%
    sensitivity analysis
    HbA1c mean difference 95% confidence interval
    −2 to −0.13%
    primary pooled analysis, orforglipron versus placebo
    HbA1c mean difference heterogeneity I²
    100%
    primary pooled analysis, orforglipron versus placebo
    HbA1c mean difference 95% confidence interval
    −1.49 to −1.41%
    sensitivity analysis, orforglipron versus placebo
    HbA1c mean difference heterogeneity I²
    0%
    sensitivity analysis, orforglipron versus placebo

    Source sentences

    Summary
    Orforglipron reduced HbA1c (primary MD − 1.07%, 95% CI − 2.00 to − 0.13; I²=100%; sensitivity MD − 1.45%, 95% CI − 1.49 to − 1.41; I²=0%),
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron reduced body weight versus placebo in both the primary and sensitivity pooled analyses.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron lowered body weight more than placebo in the main and the sensitivity pooled analyses.

    Peptide
    Orforglipron
    Outcome
    DecreaseBody weight pooled effect
    Study

    n: not reported in source

    Comparator
    placebo
    Analysis
    Primary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Body weight mean difference
    −5.25 kg
    primary pooled analysis
    Body weight mean difference
    −4.21 kg
    sensitivity analysis
    Body weight mean difference 95% confidence interval
    −6.72 to −3.77 kg
    primary pooled analysis, orforglipron versus placebo
    Body weight mean difference heterogeneity I²
    96%
    primary pooled analysis, orforglipron versus placebo
    Body weight mean difference 95% confidence interval
    −4.4 to −4.02 kg
    sensitivity analysis, orforglipron versus placebo
    Body weight mean difference heterogeneity I²
    0%
    sensitivity analysis, orforglipron versus placebo

    Source sentences

    Summary
    body weight (primary MD − 5.25 kg, 95% CI − 6.72 to − 3.77; I²=96%; sensitivity MD − 4.21 kg, 95% CI − 4.40 to − 4.02; I²=0%),
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron reduced systolic blood pressure versus placebo in both the primary and sensitivity pooled analyses.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron lowered systolic blood pressure more than placebo in the main and the sensitivity pooled analyses.

    Peptide
    Orforglipron
    Outcome
    DecreaseSystolic blood pressure pooled effect
    Study

    n: not reported in source

    Comparator
    placebo
    Analysis
    Primary
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    Systolic blood pressure mean difference
    −3.9 mmHg
    primary pooled analysis
    Systolic blood pressure mean difference
    −2.56 mmHg
    sensitivity analysis
    Systolic blood pressure mean difference 95% confidence interval
    −6.44 to −1.35 mmHg
    primary pooled analysis, orforglipron versus placebo
    Systolic blood pressure mean difference heterogeneity I²
    91%
    primary pooled analysis, orforglipron versus placebo
    Systolic blood pressure mean difference 95% confidence interval
    −4.64 to −0.48 mmHg
    sensitivity analysis, orforglipron versus placebo
    Systolic blood pressure mean difference heterogeneity I²
    22%
    sensitivity analysis, orforglipron versus placebo

    Source sentences

    Summary
    and systolic blood pressure (primary MD − 3.90 mmHg, 95% CI − 6.44 to − 1.35; I²=91%; sensitivity MD − 2.56 mmHg, 95% CI − 4.64 to − 0.48; I²=22%).
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron did not significantly change diastolic blood pressure versus placebo in the primary or sensitivity pooled analyses.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron did not significantly change diastolic blood pressure compared with placebo in the main or the sensitivity pooled analyses.

    Peptide
    Orforglipron
    Outcome
    No significant changeDiastolic blood pressure pooled effect
    Study

    n: not reported in source

    Comparator
    placebo
    Analysis
    Primary
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    Diastolic blood pressure mean difference
    −0.32 mmHg
    primary pooled analysis
    Diastolic blood pressure mean difference
    0.68 mmHg
    sensitivity analysis
    Diastolic blood pressure mean difference 95% confidence interval
    −2.36 to 1.71 mmHg
    primary pooled analysis, orforglipron versus placebo
    Diastolic blood pressure mean difference 95% confidence interval
    −0.02 to 1.39 mmHg
    sensitivity analysis, orforglipron versus placebo

    Source sentences

    Summary
    Diastolic blood pressure was neutral (primary MD − 0.32 mmHg, 95% CI − 2.36 to 1.71; sensitivity MD + 0.68 mmHg, 95% CI − 0.02 to 1.39).
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  5. 05HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron increased heart rate versus placebo.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron increased heart rate compared with placebo.

    Peptide
    Orforglipron
    Outcome
    IncreaseHeart rate
    Study

    n: not reported in source

    Comparator
    placebo
    Analysis
    Primary
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    Heart rate mean difference
    6.38 bpm
    primary pooled analysis
    Heart rate mean difference 95% confidence interval
    2.99 to 9.77 bpm
    primary pooled analysis, orforglipron versus placebo

    Source sentences

    Summary
    Heart rate increased (primary MD + 6.38 bpm, 95% CI + 2.99 to + 9.77; high heterogeneity).
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  6. 06HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron reduced BMI versus placebo.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron lowered BMI more than placebo.

    Peptide
    Orforglipron
    Outcome
    DecreaseBMI pooled effect
    Study

    n: not reported in source

    Comparator
    placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    BMI mean difference
    −1.99 kg/m²
    pooled analysis
    BMI mean difference 95% confidence interval
    −2.97 to −1.01 kg/m²
    pooled analysis, orforglipron versus placebo
    BMI mean difference heterogeneity I²
    97%
    pooled analysis, orforglipron versus placebo

    Source sentences

    Summary
    BMI (MD − 1.99 kg/m², 95% CI − 2.97 to − 1.01; I²=97%),
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  7. 07HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes and/or obesity, orforglipron significantly reduced fasting plasma glucose versus placebo, with a reported dose response.

    In plain wordsIn adults with diabetes and/or obesity, orforglipron lowered fasting blood sugar more than placebo, with a reported dose response.

    Peptide
    Orforglipron
    Outcome
    DecreaseFasting plasma glucose
    Study

    n: not reported in source

    Comparator
    placebo
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Fasting plasma glucose mean difference
    −25.77 mg/dL
    overall pooled analysis
    Fasting plasma glucose mean difference 95% confidence interval
    −58.7 to −7.18 mg/dL
    overall pooled analysis, orforglipron versus placebo

    Source sentences

    Summary
    Fasting plasma glucose decreased significantly overall (MD − 25.77 mg/dL, 95% CI − 58.70 to − 7.18; very high heterogeneity; dose-response evident).
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  8. 08HumanSystematic reviewSafety outcome

    In adults with type 2 diabetes and/or obesity, hypoglycemia risk did not significantly differ between orforglipron and placebo.

    In plain wordsIn adults with diabetes and/or obesity, low blood sugar risk did not significantly differ between orforglipron and placebo.

    Peptide
    Orforglipron
    Outcome
    No significant changeHypoglycemia
    Study

    n: not reported in source

    Comparator
    placebo
    Outcome group
    Adverse events · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Hypoglycemia risk ratio
    1.05 ratio
    orforglipron versus placebo
    Hypoglycemia risk ratio 95% confidence interval
    0.23 to 4.86 ratio
    pooled analysis, orforglipron versus placebo

    Source sentences

    Summary
    Hypoglycemia (RR 1.05, 95% CI 0.23 to 4.86) and serious adverse events (RR 1.10, 95% CI 0.75 to 1.62) did not differ from placebo.
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.
  9. 09HumanSystematic reviewSafety outcome

    In adults with type 2 diabetes and/or obesity, serious adverse event risk did not significantly differ between orforglipron and placebo.

    In plain wordsIn adults with diabetes and/or obesity, serious adverse event risk did not significantly differ between orforglipron and placebo.

    Peptide
    Orforglipron
    Outcome
    No significant changeSerious adverse events
    Study

    n: not reported in source

    Comparator
    placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated

    Measurements

    Serious adverse events risk ratio
    1.1 ratio
    orforglipron versus placebo
    Serious adverse events risk ratio 95% confidence interval
    0.75 to 1.62 ratio
    pooled analysis, orforglipron versus placebo

    Source sentences

    Summary
    Hypoglycemia (RR 1.05, 95% CI 0.23 to 4.86) and serious adverse events (RR 1.10, 95% CI 0.75 to 1.62) did not differ from placebo.
    2 context sentences
    Summary · context
    To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA).
    Summary · context
    Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals.

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

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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