Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials.

Guo H, Yang J, Huang J, Xu L, Lv Y, Wang Y, Ren J, Feng Y, Zheng Q, Li L

Obesity pillars30 Jan 2025Cited by 30 (Europe PMC)

PMID39980735PMCIDPMC11840199DOI10.1016/j.obpill.2025.100162PepBankPUB-39980735

Summary

AimObesity is a global epidemic. The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for the treatment of obesity. Clinical trials of GLP-1/GIP/glucagon(GCG) triple agonists are ongoing. This study compared the efficacy and safety profiles of different GLP-1 receptor agonists (GLP-1RAs) for weight reduction and explored the related influencing factors, providing quantitative information for the development of GLP-1RAs and their clinical use.MethodsThis systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs. Time-course, dose-response, and covariate models were used to describe the efficacy characteristics and influencing factors of different GLP-1RAs. Subgroup analyses were performed to explore efficacy differences in receptor specificity. Meta-analyses compared the incidence of adverse event and dropout rates among different GLP-1RAs.ResultsFifty-five studies involving 16,269 participants and 12 GLP-1RAs were included. Six drugs showed significant dose-response relationships. The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide). Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide). At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively. There was a significant negative correlation in the exponential pattern between age and weight reduction effect, whereas baseline weight and BMI had no significant impact. Common adverse events of GLP-1RAs, reported in the literature include nausea, vomiting, diarrhea, and constipation, with a significantly higher incidence of nausea than that of placebo.ConclusionsThis study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study18

4 results from studies that gave the peptide. 4 results from people.

01HumanSystematic reviewEfficacy outcome
In a model-based meta-analysis of placebo-controlled trials, the maximum weight reduction effect of retatrutide was 22.6 kg, the largest of the GLP-1 receptor agonists.
In plain wordsIn a pooled analysis of placebo-controlled trials, retatrutide had a maximum weight reduction of 22.6 kg, the largest among the drugs compared.
Peptide
Retatrutide
Outcome
DecreaseMaximum weight reduction effect
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Maximum weight reduction
22.6 kg
retatrutide
Source sentences
Summary
The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide).
2 context sentences(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
Summary · context
Fifty-five studies involving 16,269 participants and 12 GLP-1RAs were included.
Show in the study text Report a problemFND-3998073501
02HumanSystematic reviewEfficacy outcome
In placebo-controlled trials of adults with obesity, the model-based maximum weight reduction with liraglutide was 4.25 kg, the lowest end of the reported range across GLP-1 receptor agonists.
In plain wordsIn adults with obesity, liraglutide's maximum weight loss was 4.25 kg, the lowest in the range reported across these drugs, versus placebo.
Peptide
Liraglutide
Outcome
DecreaseMaximum weight reduction effect
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
maximum weight reduction
4.25 kg
liraglutide
Source sentences
Summary
The maximum weight reduction effect ranged from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide).
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
Show in the study text Report a problemFND-3998073502
03HumanSystematic reviewEfficacy outcome
In placebo-controlled trials of adults with obesity, the model-based onset time of the weight reduction effect of tirzepatide was 19.5 weeks, the longest of the drugs analysed.
In plain wordsIn adults with obesity, tirzepatide took 19.5 weeks to start reducing weight, the longest onset among the drugs analysed.
Peptide
Tirzepatide
Outcome
Not applicableOnset time of weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
onset time
19.5 weeks
tirzepatide
Source sentences
Summary
Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide).
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
Show in the study text Report a problemFND-3998073503
04HumanSystematic reviewEfficacy outcome
In the meta-analysis of weight reduction trials, orforglipron had a reported onset time of 6.4 weeks.
In plain wordsIn weight reduction trials, orforglipron had a reported onset time of 6.4 weeks.
Peptide
Orforglipron
Outcome
Not applicableWeight reduction onset
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Onset time
6.4 weeks
Orforglipron
Source sentences
Summary
Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide).
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
Show in the study text Report a problemFND-3998073516

Studies that did not test the peptide alone14

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.

05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In placebo-controlled trials, pooled GLP-1 receptor mono-agonists (including semaglutide) gave a model-based weight reduction of 7.03 kg at 52 weeks.
In plain wordsIn adults with obesity, GLP-1 drugs that act on one receptor, as a group including semaglutide, gave 7.03 kg weight loss at 52 weeks.
Peptide
Semaglutide
Outcome
DecreaseWeight reduction at 52 weeks, mono-agonists
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
weight reduction at 52 weeks
7.03 kg
mono-agonists
Source sentences
Summary
At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073504
06HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In placebo-controlled trials, pooled GLP-1 receptor mono-agonists (including liraglutide) gave a model-based weight reduction of 7.03 kg at 52 weeks.
In plain wordsIn adults with obesity, GLP-1 drugs that act on one receptor, as a group including liraglutide, gave 7.03 kg weight loss at 52 weeks.
Peptide
Liraglutide
Outcome
DecreaseWeight reduction at 52 weeks, mono-agonists
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
weight reduction at 52 weeks
7.03 kg
mono-agonists
Source sentences
Summary
At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073505
07HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In placebo-controlled trials, pooled dual-agonists (including tirzepatide) gave a model-based weight reduction of 11.07 kg at 52 weeks.
In plain wordsIn adults with obesity, GLP-1 drugs that act on two receptors, as a group including tirzepatide, gave 11.07 kg weight loss at 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseWeight reduction at 52 weeks, dual-agonists
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
weight reduction at 52 weeks
11.07 kg
dual-agonists
Source sentences
Summary
At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073506
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including semaglutide), age had a significant negative exponential correlation with weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including semaglutide, older age was linked to smaller weight loss.
Peptide
Semaglutide
Outcome
DecreaseAssociation of age with weight reduction effect
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
There was a significant negative correlation in the exponential pattern between age and weight reduction effect
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073507
09HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including liraglutide), age had a significant negative exponential correlation with weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including liraglutide, older age was linked to smaller weight loss.
Peptide
Liraglutide
Outcome
DecreaseAssociation of age with weight reduction effect
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
There was a significant negative correlation in the exponential pattern between age and weight reduction effect
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073508
10HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including tirzepatide), age had a significant negative exponential correlation with weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including tirzepatide, older age was linked to smaller weight loss.
Peptide
Tirzepatide
Outcome
DecreaseAssociation of age with weight reduction effect
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
There was a significant negative correlation in the exponential pattern between age and weight reduction effect
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073509
11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including semaglutide), baseline weight and BMI had no significant impact on weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including semaglutide, starting weight and BMI did not significantly change the weight loss.
Peptide
Semaglutide
Outcome
No significant changeAssociation of baseline weight and BMI with weight reduction
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
whereas baseline weight and BMI had no significant impact.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073510
12HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including liraglutide), baseline weight and BMI had no significant impact on weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including liraglutide, starting weight and BMI did not significantly change the weight loss.
Peptide
Liraglutide
Outcome
No significant changeAssociation of baseline weight and BMI with weight reduction
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
whereas baseline weight and BMI had no significant impact.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073511
13HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In the pooled model-based analysis of GLP-1 receptor agonists (including tirzepatide), baseline weight and BMI had no significant impact on weight reduction.
In plain wordsIn this pooled analysis of GLP-1 drugs including tirzepatide, starting weight and BMI did not significantly change the weight loss.
Peptide
Tirzepatide
Outcome
No significant changeAssociation of baseline weight and BMI with weight reduction
Study
n = 16,269
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
whereas baseline weight and BMI had no significant impact.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073512
14HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In placebo-controlled trials, pooled GLP-1 receptor agonists (including semaglutide) caused a significantly higher incidence of nausea than placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group, including semaglutide, caused nausea more often than placebo.
Peptide
Semaglutide
Outcome
IncreaseNausea incidence
Study
n = 16,269
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
with a significantly higher incidence of nausea than that of placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073513
15HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In placebo-controlled trials, pooled GLP-1 receptor agonists (including liraglutide) caused a significantly higher incidence of nausea than placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group, including liraglutide, caused nausea more often than placebo.
Peptide
Liraglutide
Outcome
IncreaseNausea incidence
Study
n = 16,269
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
with a significantly higher incidence of nausea than that of placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073514
16HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In placebo-controlled trials, pooled GLP-1 receptor agonists (including tirzepatide) caused a significantly higher incidence of nausea than placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group, including tirzepatide, caused nausea more often than placebo.
Peptide
Tirzepatide
Outcome
IncreaseNausea incidence
Study
n = 16,269
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
with a significantly higher incidence of nausea than that of placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073515
17HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome
In the meta-analysis, pooled mono-agonists produced a weight reduction effect of 7.03 kg at 52 weeks.
In plain wordsIn the meta-analysis, pooled mono-agonists produced a weight reduction effect of 7.03 kg at 52 weeks.
Peptide
Orforglipron
Outcome
DecreaseWeight reduction with mono-agonists
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight reduction
7.03 kg
mono-agonists at 52 weeks
Source sentences
Summary
At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073517
18HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome
In the meta-analysis, pooled GLP-1RAs had a significantly higher incidence of nausea than placebo.
In plain wordsIn the meta-analysis, pooled GLP-1RAs had more nausea than placebo.
Peptide
Orforglipron
Outcome
IncreaseNausea incidence
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Common adverse events of GLP-1RAs, reported in the literature include nausea, vomiting, diarrhea, and constipation, with a significantly higher incidence of nausea than that of placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
This systematic review of public databases included placebo-controlled randomized clinical trials of GLP-1RAs.
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.
Show in the study text Report a problemFND-3998073521

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.

Versions 30 to 47Current
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
Version 29
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Versions 5 to 28
13 Oct 2026, 21:46 UTC
The same notice was added 24 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.
Study results updated
Versions 2 to 4
9 Oct 2026, 03:07 UTC
The same notice was added 3 times, first on 9 Oct 2026, 03:05 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials.

Summary

Results from this study18

Studies that did not test the peptide alone14

Version history

Subjects

Publication types

Keywords