Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials.

Chen D, Ma B, Sun H, Zhang J, Gong L, Wang W, Liu Z, Zha H, Du S, Chen M, Sun W, Guo Q, Cao Y, Li Y

BMJ medicine27 Aug 2026

PMID42688617PMCIDPMC13536023DOI10.1136/bmjmed-2026-003026PepBankPUB-42688617

Read at source PubMedAsk about this study

Summary

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

Text rights: CC BY-NC. Results still quote short attributed sentences.

Results from this study7

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

01HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, mazdutide showed better tolerability, whereas discontinuation was higher with danuglipron and retatrutide (low certainty evidence).
In plain wordsIn adults with overweight or obesity without diabetes, a pooled analysis suggested mazdutide was better tolerated, with low certainty and no clear comparator.
Peptide
Mazdutide
Outcome
Direction not reportedTolerability
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability.
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
Report a problemFND-4268861702
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, retatrutide produced the greatest weight loss versus placebo in a network meta-analysis (-22.10%).
In plain wordsIn adults with overweight or obesity, retatrutide gave the largest weight loss compared with placebo among the drugs compared.
Peptide
Retatrutide
Outcome
DecreaseWeight change versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
weight change
−22.1%
retatrutide vs placebo
Source sentences
Summary
Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%).
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
Report a problemFND-4268861703
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, tirzepatide reduced weight versus placebo in a network meta-analysis (-19.28%).
In plain wordsIn adults with overweight or obesity, tirzepatide led to weight loss compared with placebo.
Peptide
Tirzepatide
Outcome
DecreaseWeight change versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
weight change
−19.28%
tirzepatide vs placebo
Source sentences
Summary
Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%).
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
Report a problemFND-4268861704
04HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, low certainty evidence suggested higher rates of treatment discontinuation with retatrutide.
In plain wordsIn adults with overweight or obesity, low certainty evidence suggested more people stopped retatrutide.
Peptide
Retatrutide
Outcome
IncreaseTreatment discontinuation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability.
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
Report a problemFND-4268861707

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.

05HumanNot a test of Cagrilintide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, CagriSema reduced body weight by 17.32% compared with placebo in a network meta-analysis.
In plain wordsIn adults with overweight or obesity without diabetes, CagriSema led to weight loss compared with placebo in a pooled analysis of trials.
Peptide
Cagrilintide
Outcome
DecreasePercent weight loss with CagriSema
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Weight loss versus placebo
−17.32%
CagriSema
Source sentences
Summary
Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%)
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
In this study, Cagrilintide 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 Cagrilintide.
Report a problemFND-4268861701
06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, CagriSema (cagrilintide plus semaglutide) reduced weight versus placebo in a network meta-analysis (-17.32%).
In plain wordsIn adults with overweight or obesity, CagriSema, a mix of two drugs, led to weight loss compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseWeight change versus placebo (CagriSema)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
weight change
−17.32%
CagriSema vs placebo
Source sentences
Summary
Compared with placebo, weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema (a combination of cagrilintide and semaglutide, -17.32%, -19.32% to -15.32%).
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
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.
Report a problemFND-4268861705
07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, conventional GLP-1 receptor agonists as a class showed more modest weight loss than next-generation agents.
In plain wordsIn adults with overweight or obesity, older GLP-1 drugs as a group led to smaller weight loss than newer drugs.
Peptide
Semaglutide
Outcome
DecreaseWeight loss with conventional GLP-1 receptor agonists
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Conventional GLP-1 receptor agonists showed more modest effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Randomised controlled trials that enrolled adults with overweight or obesity, comparing GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks.
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.
Report a problemFND-4268861706

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 6 to 41Current
28 Oct 2026, 02:04 UTC
The same notice was added 36 times, first on 9 Oct 2026, 18:17 UTC. The status did not change between them.
Study results updated
Versions 2 to 5
9 Oct 2026, 03:07 UTC
The same notice was added 4 times, first on 9 Oct 2026, 03:04 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Comparative efficacy and safety of glucagon-like peptide 1 based drugs for weight loss in adults with overweight or obesity without diabetes: network meta-analysis of randomised controlled trials.

Summary

Results from this study7

Studies that did not test the peptide alone3

Version history

Subjects

Publication types

Keywords