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Study · Systematic review · 2023

15 results

Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review.

Xie Z, Hu J, Gu H, Li M, Chen J

Frontiers in endocrinology28 Aug 2023Cited by 37 (Europe PMC)

PMID37701904 (opens in a new tab)PMCIDPMC10493284 (opens in a new tab)DOI10.3389/fendo.2023.1244432 (opens in a new tab)PepBankPUB-37701904
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Summary

PurposeThis study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.MethodsThree databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.Results34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.ConclusionThis study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study15

12 results from studies that gave the peptide. 12 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, tirzepatide 15 mg reduced HbA1c by 2.23%.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, tirzepatide 15 mg given with background metformin lowered HbA1c.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c change (tirzepatide 15 mg)
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    15 mgAs given in this study (human).

    Measurements

    HbA1c change
    −2.23%
    tirzepatide 15 mg

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  2. 02HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, tirzepatide 15 mg reduced body weight by 11.33 kg.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, tirzepatide 15 mg given with background metformin lowered body weight.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight change (tirzepatide 15 mg)
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    15 mgAs given in this study (human).

    Measurements

    body weight change
    −11.33 kg
    tirzepatide 15 mg

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  3. 03HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, tirzepatide 15 mg showed no significant difference in the rate of adverse events.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, tirzepatide 15 mg showed no significant difference in side-effect rate.

    Peptide
    Tirzepatide
    Outcome
    No significant changeRate of adverse events (tirzepatide 15 mg)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  4. 04HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, tirzepatide 15 mg differed significantly from placebo in the rate of serious adverse events; the abstract does not give the direction.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, tirzepatide 15 mg differed from placebo in serious side-effect rate.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedRate of serious adverse events (tirzepatide 15 mg)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  5. 05HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, semaglutide 1.0 mg reduced HbA1c by 1.57%.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, semaglutide 1.0 mg given with background metformin lowered HbA1c.

    Peptide
    Semaglutide
    Outcome
    DecreaseHbA1c change (semaglutide 1.0 mg)
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    1.0 mgAs given in this study (human).

    Measurements

    HbA1c change
    −1.57%
    semaglutide 1.0 mg

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  6. 06HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, semaglutide 1.0 mg reduced body weight by 5.99 kg.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, semaglutide 1.0 mg given with background metformin lowered body weight.

    Peptide
    Semaglutide
    Outcome
    DecreaseBody weight change (semaglutide 1.0 mg)
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.0 mgAs given in this study (human).

    Measurements

    body weight change
    −5.99 kg
    semaglutide 1.0 mg

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  7. 07HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, oral semaglutide 14 reduced HbA1c by 1.10%.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, oral semaglutide given with background metformin lowered HbA1c.

    Peptide
    Semaglutide
    Outcome
    DecreaseHbA1c change (oral semaglutide 14 mg)
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    14 mg · oralAs given in this study (human).

    Measurements

    HbA1c change
    −1.1%
    oral semaglutide 14

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  8. 08HumanSystematic reviewEfficacy outcome

    In a network meta-analysis of trials with background metformin in type 2 diabetes, oral semaglutide 14 reduced body weight by 3.95 kg.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, oral semaglutide given with background metformin lowered body weight.

    Peptide
    Semaglutide
    Outcome
    DecreaseBody weight change (oral semaglutide 14 mg)
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    14 mg · oralAs given in this study (human).

    Measurements

    body weight change
    −3.95 kg
    oral semaglutide 14

    Source sentences

    Summary
    According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  9. 09HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, semaglutide 1.0 mg showed no significant difference in the rate of adverse events.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, semaglutide 1.0 mg showed no significant difference in side-effect rate.

    Peptide
    Semaglutide
    Outcome
    No significant changeRate of adverse events (semaglutide 1.0 mg)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  10. 10HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, oral semaglutide 14 mg showed no significant difference in the rate of adverse events.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, oral semaglutide 14 mg showed no significant difference in side-effect rate.

    Peptide
    Semaglutide
    Outcome
    No significant changeRate of adverse events (oral semaglutide 14 mg)
    Study

    n: not reported in source

    Outcome group
    Adverse events · Whole body
    Studied dose
    14 mg · oralAs given in this study (human).

    Source sentences

    Summary
    There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  11. 11HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, oral semaglutide 14mg differed significantly from placebo in the rate of serious adverse events; the abstract does not give the direction.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, oral semaglutide differed from placebo in serious side-effect rate.

    Peptide
    Semaglutide
    Outcome
    Direction not reportedRate of serious adverse events (oral semaglutide 14 mg)
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Adverse events · Whole body
    Studied dose
    14 mg · oralAs given in this study (human).

    Source sentences

    Summary
    only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).
  12. 12HumanSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, semaglutide 1.0 mg differed significantly from placebo in withdrawal because of adverse events; the abstract does not give the direction.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, semaglutide 1.0 mg differed from placebo in stopping treatment because of side effects.

    Peptide
    Semaglutide
    Outcome
    Direction not reportedAdverse event withdrawal (semaglutide 1.0 mg)
    Study

    n: not reported in source

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

    Source sentences

    Summary
    Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal.
    1 context sentence
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).

Studies that did not test the peptide alone3

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. 13HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, no GLP-1 receptor agonist, tirzepatide included, increased the incidence of hypoglycemia.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, none of the GLP-1 drugs, tirzepatide included, raised low blood sugar risk.

    Peptide
    Tirzepatide
    Outcome
    No significant changeHypoglycemia incidence (all GLP-1RAs pooled)
    Study

    n: not reported in source

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    All GLP-1RA did not lead to increased incidence of hypoglycemia.
    2 context sentences
    Summary · context
    The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).

    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.

  2. 14HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, no GLP-1 receptor agonist, semaglutide included, increased the incidence of hypoglycemia.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, none of the GLP-1 drugs, semaglutide included, raised low blood sugar risk.

    Peptide
    Semaglutide
    Outcome
    No significant changeHypoglycemia incidence (all GLP-1RAs pooled)
    Study

    n: not reported in source

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    All GLP-1RA did not lead to increased incidence of hypoglycemia.
    2 context sentences
    Summary · context
    The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).

    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. 15HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome

    In a network meta-analysis of trials with background metformin, no GLP-1 receptor agonist, liraglutide included, increased the incidence of hypoglycemia.

    In plain wordsIn a pooled analysis of trials in type 2 diabetes, none of the GLP-1 drugs, liraglutide included, raised low blood sugar risk.

    Peptide
    Liraglutide
    Outcome
    No significant changeHypoglycemia incidence (all GLP-1RAs pooled)
    Study

    n: not reported in source

    Outcome group
    Adverse events · Metabolic and weight

    Source sentences

    Summary
    All GLP-1RA did not lead to increased incidence of hypoglycemia.
    2 context sentences
    Summary · context
    The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
    Summary · context
    34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA).

    In this study, Liraglutide 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 Liraglutide.

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 4Current

    12 Oct 2026, 11:11 UTC

    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, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  3. 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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