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Study · Systematic review · 2026

24 results

Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus: a network meta-analysis based on clinical trials.

Wu X, Yang Y, Cui X, Li X, Li Y

Frontiers in pharmacology18 Jun 2026

PMID42394981 (opens in a new tab)PMCIDPMC13322860 (opens in a new tab)DOI10.3389/fphar.2026.1846714 (opens in a new tab)PepBankPUB-42394981
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Summary

ObjectivesThis study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.MethodsA systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746). We searched MEDLINE, Cochrane Library, and Embase up to 1 August 2025, for randomized controlled trials (RCTs). Study selection, data extraction, risk-of-bias assessment (Cochrane RoB 2.0) and CINeMA framework were conducted. Analyses included SUCRA ranking, sensitivity, subgroup, and meta-regression in R Studio 4.4.3.Results102 RCTs (98,693 T2DM patients) with low overall bias were included. IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement. The most common adverse events were mild, transient gastrointestinal reactions, and the risk of hypoglycemia was low. Higher doses improved efficacy but increased adverse events; 45 mg orforglipron balanced benefits and tolerability. Optimal duration and combination efficacy varied by agent.ConclusionIBTs provide comprehensive benefits in T2DM. Efficacy and safety differ across agents, doses, durations, and combinations, supporting individualized therapy. Long-term high-quality RCTs are needed. Cardiovascular protection may stem from synergistic improvements in lipids, blood pressure, renal function, and insulin sensitivity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251152746.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study24

5 results from studies that gave the peptide. 5 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials in type 2 diabetes, retatrutide ranked best for weight loss among incretin-based therapies, which were superior to placebo.

    In plain wordsIn a pooled analysis in type 2 diabetes, retatrutide ranked best for weight loss among 15 incretin-based drugs, which as a group beat placebo.

    Peptide
    Retatrutide
    Outcome
    DecreaseWeight loss versus placebo in type 2 diabetes
    Study

    n: not reported in source

    Comparator
    Other incretin-based therapies (ranking) and placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, semaglutide was among the best of 15 incretin-based therapies for glycemic control versus placebo, with tirzepatide and orforglipron.

    In plain wordsIn adults with type 2 diabetes, semaglutide was among the best drugs for blood sugar control compared with placebo, alongside tirzepatide and orforglipron.

    Peptide
    Semaglutide
    Outcome
    Not applicableGlycemic control (best-ranked agents)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best)
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, tirzepatide was among the best of 15 incretin-based therapies for glycemic control versus placebo, with orforglipron and semaglutide.

    In plain wordsIn adults with type 2 diabetes, tirzepatide was among the best drugs for blood sugar control compared with placebo, alongside orforglipron and semaglutide.

    Peptide
    Tirzepatide
    Outcome
    Not applicableGlycemic control (best-ranked agents)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best)
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.
  4. 04HumanSystematic reviewEfficacy outcome

    In patients with diabetes, orforglipron ranked among the best therapies for glycemic control and was superior to placebo.

    In plain wordsIn patients with diabetes, orforglipron ranked among the best therapies for blood sugar control and was superior to placebo.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedGlycemic control ranking
    Study

    n: not reported in source

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

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).
  5. 05HumanSystematic reviewOther

    In patients with diabetes, orforglipron 45 mg balanced benefits and tolerability, without specific results in this sentence.

    In plain wordsIn patients with diabetes, orforglipron 45 mg balanced benefits and tolerability, without specific results in this sentence.

    Peptide
    Orforglipron
    Outcome
    Not applicableBenefit and tolerability balance
    Study

    n: not reported in source

    Outcome group
    Adverse events · Whole body
    Studied dose
    45 mgAs given in this study (human).

    Source sentences

    Summary
    Higher doses improved efficacy but increased adverse events; 45 mg orforglipron balanced benefits and tolerability.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

Studies that did not test the peptide alone19

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

  1. 06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo in glycemic control.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group improved blood sugar control more than placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableGlycemic control, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best)
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  2. 07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo for weight loss.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group led to more weight loss than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseWeight loss, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  3. 08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo for lipid improvement.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group improved blood fat levels more than placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableLipids, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  4. 09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo for blood pressure improvement.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group improved blood pressure more than placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableBlood pressure, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Blood pressure · Cardiovascular

    Source sentences

    Summary
    lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  5. 10HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo for cardiorenal improvement.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group improved heart and kidney measures more than placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableCardiorenal outcomes, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular

    Source sentences

    Summary
    lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  6. 11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pooled incretin-based therapies, including semaglutide, were superior to placebo for insulin function improvement.

    In plain wordsIn adults with type 2 diabetes, the incretin-based drugs as a group improved insulin function more than placebo.

    Peptide
    Semaglutide
    Outcome
    Not applicableInsulin function, pooled incretin-based therapies
    Study

    n = 98,693

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    lipid, blood pressure, cardiorenal, and insulin function improvement.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  7. 12HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In adults with type 2 diabetes, the most common adverse events of pooled incretin-based therapies, including semaglutide, were mild, transient gastrointestinal reactions.

    In plain wordsIn adults with type 2 diabetes, the most common side effects of the incretin-based drugs as a group were mild, short-lived stomach and gut problems.

    Peptide
    Semaglutide
    Outcome
    Not applicableCommon adverse events, pooled incretin-based therapies
    Study

    n = 98,693

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal

    Source sentences

    Summary
    The most common adverse events were mild, transient gastrointestinal reactions, and the risk of hypoglycemia was low.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  8. 13HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In adults with type 2 diabetes, the risk of hypoglycemia with pooled incretin-based therapies, including semaglutide, was low.

    In plain wordsIn adults with type 2 diabetes, the risk of low blood sugar with the incretin-based drugs as a group was low.

    Peptide
    Semaglutide
    Outcome
    Not applicableHypoglycemia risk, pooled incretin-based therapies
    Study

    n = 98,693

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    the risk of hypoglycemia was low.
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  9. 14HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, higher doses of pooled incretin-based therapies, including semaglutide, improved efficacy.

    In plain wordsIn adults with type 2 diabetes, higher doses of the incretin-based drugs as a group worked better.

    Peptide
    Semaglutide
    Outcome
    IncreaseEfficacy at higher doses, pooled incretin-based therapies
    Study

    n = 98,693

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Higher doses improved efficacy but increased adverse events
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  10. 15HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In adults with type 2 diabetes, higher doses of pooled incretin-based therapies, including semaglutide, increased adverse events.

    In plain wordsIn adults with type 2 diabetes, higher doses of the incretin-based drugs as a group caused more side effects.

    Peptide
    Semaglutide
    Outcome
    IncreaseAdverse events at higher doses, pooled incretin-based therapies
    Study

    n = 98,693

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    Higher doses improved efficacy but increased adverse events
    1 context sentence
    Summary · context
    102 RCTs (98,693 T2DM patients) with low overall bias were included.

    In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.

  11. 16HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron improved weight loss versus placebo.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies improved weight loss versus placebo.

    Peptide
    Orforglipron
    Outcome
    DecreaseWeight loss
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  12. 17HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron improved lipids versus placebo without a specified lipid measure.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies improved lipids versus placebo without a specified lipid measure.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedLipids
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Lipids · Metabolic and weight

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  13. 18HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron improved blood pressure versus placebo.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies improved blood pressure versus placebo.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedBlood pressure
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Blood pressure · Cardiovascular

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  14. 19HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron improved unspecified cardiorenal outcomes versus placebo.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies improved unspecified heart and kidney outcomes versus placebo.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedCardiorenal outcomes
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Overall treatment effect · Whole body

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  15. 20HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron improved insulin function versus placebo.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies improved insulin function versus placebo.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedInsulin function
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    IBTs were superior to placebo in glycemic control (tirzepatide, orforglipron, semaglutide best), weight loss (retatrutide best), lipid, blood pressure, cardiorenal, and insulin function improvement.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  16. 21HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron had mild, transient gastrointestinal reactions as the most common adverse events.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies had mostly mild, temporary gastrointestinal reactions as the most common adverse events.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedGastrointestinal reactions
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal

    Source sentences

    Summary
    The most common adverse events were mild, transient gastrointestinal reactions, and the risk of hypoglycemia was low.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  17. 22HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome

    In patients with diabetes, pooled incretin-based therapies including orforglipron had low hypoglycemia risk.

    In plain wordsIn patients with diabetes, pooled incretin-based therapies had low risk of low blood sugar.

    Peptide
    Orforglipron
    Outcome
    Direction not reportedHypoglycemia risk
    Study

    n: not reported in source

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    The most common adverse events were mild, transient gastrointestinal reactions, and the risk of hypoglycemia was low.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  18. 23HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome

    In patients with diabetes, higher doses of pooled incretin-based therapies including orforglipron improved unspecified efficacy outcomes.

    In plain wordsIn patients with diabetes, higher doses of pooled incretin-based therapies improved unspecified efficacy outcomes compared with lower doses.

    Peptide
    Orforglipron
    Outcome
    IncreaseDose-related efficacy
    Study

    n: not reported in source

    Comparator
    Lower doses
    Outcome group
    Overall treatment effect · Metabolic and weight

    Source sentences

    Summary
    Higher doses improved efficacy but increased adverse events; 45 mg orforglipron balanced benefits and tolerability.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

  19. 24HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome

    In patients with diabetes, higher doses of pooled incretin-based therapies including orforglipron increased adverse events.

    In plain wordsIn patients with diabetes, higher doses of pooled incretin-based therapies increased adverse events compared with lower doses.

    Peptide
    Orforglipron
    Outcome
    IncreaseDose-related adverse events
    Study

    n: not reported in source

    Comparator
    Lower doses
    Outcome group
    Adverse events · Whole body

    Source sentences

    Summary
    Higher doses improved efficacy but increased adverse events; 45 mg orforglipron balanced benefits and tolerability.
    2 context sentences
    Summary · context
    This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
    Summary · context
    A systematic review and Bayesian network meta-analysis were performed following PRISMA 2020 and PRISMA-NMA guidelines (PROSPERO: CRD420251152746).

    In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.

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. Versions 29 to 46Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 18 times, first on 14 Oct 2026, 05:01 UTC. The status did not change between them.

    Study results updated

  2. Version 28

    14 Oct 2026, 01:46 UTC

    Study data updated · source update from Europe PMC

  3. Versions 4 to 27

    13 Oct 2026, 21:46 UTC

    The same notice was added 24 times, first on 9 Oct 2026, 18:17 UTC. The status did not change between them.

    Study results updated

  4. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

    The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  5. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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