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Study · Systematic review · 2025

12 results

Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis.

Liu S, Hu J, Zhao C, Liu H, He C

Frontiers in endocrinology4 Feb 2025Cited by 12 (Europe PMC)

PMID39968298 (opens in a new tab)PMCIDPMC11832366 (opens in a new tab)DOI10.3389/fendo.2025.1513641 (opens in a new tab)PepBankPUB-39968298
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Summary

BackgroundThe rapid development of multi-receptor drugs targeting glucagon-like peptide-1 receptor (GLP-1R) is driving significant advancements in the treatment of individuals with type 2 diabetes and obesity. This systematic review and network meta-analysis aims to compare the efficacy and safety of multi-receptor drugs in adults with overweight or obesity, with or without type 2 diabetes.MethodsA systematic search was conducted in PubMed, Cochrane, Web of Science, Embase, CNKI, and WanFang databases up to May 12, 2024. Randomized controlled trials (RCTs) with an intervention duration of at least 12 weeks were included. The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes. Eligible studies compared multi-receptor drugs with placebo or other multi-receptor drugs. The primary outcomes were weight reduction, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), blood pressure changes, and adverse events. Risk of bias was assessed using the version 2 of the Cochrane risk-of-bias tool (ROB2), and a random-effects network meta-analysis was performed using the frequentist approach. Confidence in effect estimates was evaluated using the Confidence In Network Meta-Analysis (CINeMA) framework.ResultsA total of 24 trials, involving 9165 participants, were included. Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 to -4.82, P-score: 0.80, p: 0.0003) and Tirzepatide (MD: -12.78 kg, 95% CI: -16.10 to -9.46, P-score: 0.89, p < 0.0001) exhibited superior efficacy in reducing body weight, with all other agents except Mazdutide (MD: -5.31 kg, 95% CI: -9.78 to -0.84, P-score: 0.37, p: 0.0189) achieving reductions of over 8 kg. In patients with type 2 diabetes, all agents reduced HbA1c by over 1%, with Tirzepatide (MD: -1.87%, 95% CI: -2.15 to -1.59, P-score: 0.87, p < 0.0001) and Mazdutide (MD: -1.89%, 95% CI: -2.43 to -1.35, P-score: 0.88, p < 0.0001) showing the greatest effects on glycemic control. For blood pressure management, Tirzepatide significantly reduced systolic blood pressure (MD: -6.69 mmHg, 95% CI: -7.62 to -5.75, P-score: 0.84, p < 0.0001) and diastolic blood pressure (MD: -3.73 mmHg, 95% CI: -4.75 to -2.71, P-score: 0.92, p < 0.0001), with nearly all agents lowering systolic blood pressure by more than 5 mmHg. Non-diabetic participants showed more pronounced improvements in both weight and blood pressure. Safety analysis revealed that Tirzepatide had a favorable safety profile and all agents showed no significant impact on serious adverse events compared to placebo.ConclusionsMulti-receptor drugs demonstrated substantial therapeutic potential in weight management, glycemic control, and blood pressure regulation in adults with overweight or obesity, with or without diabetes, with a generally favorable safety profile.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024554005.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, retatrutide reduced body weight by a mean difference of 11.91 kg in a network meta-analysis of RCTs.

    In plain wordsIn adults with overweight or obesity, retatrutide reduced body weight by about 12 kg in a pooled comparison of trials.

    Peptide
    Retatrutide
    Outcome
    DecreaseBody weight change (network meta-analysis)
    Study

    n: not reported in source

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

    Measurements

    Body weight, mean difference
    −11.91 kg
    retatrutide

    Source sentences

    Summary
    Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 to -4.82, P-score: 0.80, p: 0.0003)
    1 context sentence
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide reduced body weight (MD -12.78 kg) in the network meta-analysis.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to more weight loss in a pooled analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight reduction
    Study

    n: not reported in source

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

    Measurements

    MD body weight
    −12.78 kg
    tirzepatide

    Source sentences

    Summary
    Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 to -4.82, P-score: 0.80, p: 0.0003) and Tirzepatide (MD: -12.78 kg, 95% CI: -16.10 to -9.46, P-score: 0.89, p < 0.0001) exhibited superior efficacy in reducing body weight, with all other agents except Mazdutide (MD: -5.31 kg, 95% CI: -9.78 to -0.84, P-score: 0.37, p: 0.0189) achieving reductions of over 8 kg.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity and type 2 diabetes, tirzepatide reduced HbA1c (MD -1.87%) in the network meta-analysis.

    In plain wordsIn adults with obesity and type 2 diabetes, tirzepatide was linked to a lower HbA1c in a pooled analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c reduction in type 2 diabetes
    Study

    n: not reported in source

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

    Measurements

    MD HbA1c
    −1.87%
    tirzepatide

    Source sentences

    Summary
    In patients with type 2 diabetes, all agents reduced HbA1c by over 1%, with Tirzepatide (MD: -1.87%, 95% CI: -2.15 to -1.59, P-score: 0.87, p < 0.0001) and Mazdutide (MD: -1.89%, 95% CI: -2.43 to -1.35, P-score: 0.88, p < 0.0001) showing the greatest effects on glycemic control.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.
  4. 04HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide significantly reduced systolic blood pressure (MD -6.69 mmHg) in the network meta-analysis.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to lower systolic blood pressure in a pooled analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseSystolic blood pressure reduction
    Study

    n: not reported in source

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

    Measurements

    MD systolic blood pressure
    −6.69 mmHg
    tirzepatide

    Source sentences

    Summary
    For blood pressure management, Tirzepatide significantly reduced systolic blood pressure (MD: -6.69 mmHg, 95% CI: -7.62 to -5.75, P-score: 0.84, p < 0.0001) and diastolic blood pressure (MD: -3.73 mmHg, 95% CI: -4.75 to -2.71, P-score: 0.92, p < 0.0001), with nearly all agents lowering systolic blood pressure by more than 5 mmHg.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.
  5. 05HumanSystematic reviewEfficacy outcome

    In adults with overweight or obesity, tirzepatide significantly reduced diastolic blood pressure (MD -3.73 mmHg) in the network meta-analysis.

    In plain wordsIn adults with overweight or obesity, tirzepatide was linked to lower diastolic blood pressure in a pooled analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseDiastolic blood pressure reduction
    Study

    n: not reported in source

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

    Measurements

    MD diastolic blood pressure
    −3.73 mmHg
    tirzepatide

    Source sentences

    Summary
    For blood pressure management, Tirzepatide significantly reduced systolic blood pressure (MD: -6.69 mmHg, 95% CI: -7.62 to -5.75, P-score: 0.84, p < 0.0001) and diastolic blood pressure (MD: -3.73 mmHg, 95% CI: -4.75 to -2.71, P-score: 0.92, p < 0.0001), with nearly all agents lowering systolic blood pressure by more than 5 mmHg.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.
  6. 06HumanSystematic reviewSafety outcome

    In the network meta-analysis, tirzepatide was reported to have a favorable safety profile.

    In plain wordsIn a pooled analysis, tirzepatide was reported to have a favorable safety profile.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedSafety profile
    Study

    n: not reported in source

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

    Source sentences

    Summary
    Safety analysis revealed that Tirzepatide had a favorable safety profile
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.

Studies that did not test the peptide alone6

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. 07HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome

    In patients with type 2 diabetes, all agents in the network meta-analysis, retatrutide included, reduced HbA1c by over 1%.

    In plain wordsIn people with type 2 diabetes, all drugs compared, including retatrutide, lowered HbA1c by more than 1 percentage point in a pooled analysis.

    Peptide
    Retatrutide
    Outcome
    DecreaseHbA1c reduction in type 2 diabetes
    Study

    n: not reported in source

    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight

    Measurements

    HbA1c reduction
    > 1%
    all agents

    Source sentences

    Summary
    all agents reduced HbA1c by over 1%
    1 context sentence
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.

    In this study, Retatrutide 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 Retatrutide.

  2. 08HumanNot a test of Retatrutide aloneSystematic reviewSafety outcome

    In adults with overweight or obesity, all agents in the network meta-analysis, retatrutide included, showed no significant impact on serious adverse events compared with placebo.

    In plain wordsIn adults with overweight or obesity, retatrutide and the other drugs compared did not significantly change serious side effects compared with placebo.

    Peptide
    Retatrutide
    Outcome
    No significant changeSerious adverse events versus placebo
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Adverse events · Whole body

    Source sentences

    Summary
    all agents showed no significant impact on serious adverse events compared to placebo.
    1 context sentence
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.

    In this study, Retatrutide 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 Retatrutide.

  3. 09HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome

    In the network meta-analysis, all multi-receptor agents pooled (including tirzepatide) showed no significant impact on serious adverse events compared with placebo.

    In plain wordsIn a pooled analysis, the multi-receptor drugs as a group did not significantly change serious adverse events compared with placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changeSerious adverse events, all agents pooled
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body

    Source sentences

    Summary
    all agents showed no significant impact on serious adverse events compared to placebo.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.

    In this study, Tirzepatide 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 Tirzepatide.

  4. 10HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    In patients with type 2 diabetes, all multi-receptor agents pooled (including tirzepatide) reduced HbA1c by over 1%.

    In plain wordsIn people with type 2 diabetes, the multi-receptor drugs as a group each lowered HbA1c by more than 1%.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c reduction, all agents pooled
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    In patients with type 2 diabetes, all agents reduced HbA1c by over 1%
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.

    In this study, Tirzepatide 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 Tirzepatide.

  5. 11HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    Nearly all multi-receptor agents, tirzepatide among them, lowered systolic blood pressure by more than 5 mmHg.

    In plain wordsNearly all the multi-receptor drugs as a group lowered systolic blood pressure by more than 5 mmHg.

    Peptide
    Tirzepatide
    Outcome
    DecreaseSystolic blood pressure, nearly all agents pooled
    Study

    n: not reported in source

    Outcome group
    Blood pressure · Cardiovascular

    Source sentences

    Summary
    with nearly all agents lowering systolic blood pressure by more than 5 mmHg.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.

    In this study, Tirzepatide 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 Tirzepatide.

  6. 12HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome

    Non-diabetic participants showed more pronounced improvements in both weight and blood pressure across pooled multi-receptor drugs.

    In plain wordsPeople without diabetes showed larger improvements in weight and blood pressure across the multi-receptor drugs as a group.

    Peptide
    Tirzepatide
    Outcome
    Not applicableWeight and blood pressure by diabetes status
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight

    Source sentences

    Summary
    Non-diabetic participants showed more pronounced improvements in both weight and blood pressure.
    2 context sentences
    Summary · context
    The population of interest consisted of individuals with overweight or obesity, with or without type 2 diabetes.
    Summary · context
    A total of 24 trials, involving 9165 participants, were included.

    In this study, Tirzepatide 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 Tirzepatide.

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 4 to 39Current

    28 Oct 2026, 02:04 UTC

    The same notice was added 36 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.

    Study results updated

  2. Versions 2 to 3

    9 Oct 2026, 03:07 UTC

    The same notice was added 2 times, first on 9 Oct 2026, 03:04 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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