Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.

Nong K, Shi Q, Xie X, Wang Y, Agarwal A, Guyatt GH, Zhang H, Gao Y, Khunti K, Le Roux CW, Widyahening IS, Fan Q and 17 more

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Liu T, Mao Y, Florez ID, Du H, Pan X, Zou X, Wang C, Sun X, Li J, Hao Q, Jia Q, Sun F, Zhu Z, Agoritsas T, Tian H, Vandvik PO, Li S

BMJ (Clinical research ed.)8 Jul 2026Cited by 2 (Europe PMC)

PMID42419792DOI10.1136/bmj-2026-372161PepBankPUB-42419792

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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 study29

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

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, tirzepatide reduced body weight at one year by a mean difference of -14.9% versus lifestyle modification alone.
In plain wordsIn adults with overweight or obesity, tirzepatide led to substantial weight loss at one year compared with lifestyle change alone.
Peptide
Tirzepatide
Outcome
DecreaseWeight loss at one year
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 1 yearAs given in this study (human).
Measurements
Mean difference in weight
−14.9%
tirzepatide vs lifestyle modification
Source sentences
Summary
tirzepatide (mean difference -14.9%, 95% confidence interval -16.0% to -13.9%)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979206
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, oral semaglutide reduced body weight at one year by a mean difference of -10.9% versus lifestyle modification alone.
In plain wordsIn adults with overweight or obesity, oral semaglutide led to substantial weight loss at one year compared with lifestyle change alone.
Peptide
Semaglutide
Outcome
DecreaseWeight loss at one year (oral semaglutide)
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · oral · 1 yearAs given in this study (human).
Measurements
Mean difference in weight
−10.9%
oral semaglutide vs lifestyle modification
Source sentences
Summary
oral semaglutide (-10.9%, -12.7% to -9.1%)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979208
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, subcutaneous semaglutide reduced body weight at one year by a mean difference of -9.8% versus lifestyle modification alone.
In plain wordsIn adults with overweight or obesity, injected semaglutide led to substantial weight loss at one year compared with lifestyle change alone.
Peptide
Semaglutide
Outcome
DecreaseWeight loss at one year (subcutaneous semaglutide)
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneous · 1 yearAs given in this study (human).
Measurements
Mean difference in weight
−9.8%
subcutaneous semaglutide vs lifestyle modification
Source sentences
Summary
subcutaneous semaglutide (-9.8%, -10.6% to -9.1%)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979209
04HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, tirzepatide reduced fat mass the most, by 25.7%.
In plain wordsIn adults with overweight or obesity, tirzepatide reduced fat mass more than the other drugs studied.
Peptide
Tirzepatide
Outcome
DecreaseFat mass reduction
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Fat mass reduction
25.7%
tirzepatide
Source sentences
Summary
Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (by 8.3%).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979215
05HumanSystematic reviewSafety outcome
In adults with overweight or obesity, tirzepatide also reduced lean mass the most, by 8.3%.
In plain wordsIn adults with overweight or obesity, tirzepatide also reduced lean body mass more than the other drugs studied.
Peptide
Tirzepatide
Outcome
DecreaseLean mass reduction
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Lean mass reduction
8.3%
tirzepatide
Source sentences
Summary
Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (by 8.3%).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979216
06HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, subcutaneous semaglutide was the only drug associated with reduced all-cause mortality (risk ratio 0.81).
In plain wordsIn adults with overweight or obesity, injected semaglutide was the only drug linked to fewer deaths from any cause.
Peptide
Semaglutide
Outcome
DecreaseAll-cause mortality
Study
n: not reported in source
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
Risk ratio all-cause mortality
0.81
subcutaneous semaglutide
Source sentences
Summary
Subcutaneous semaglutide was the only drug associated with reduced all cause mortality (risk ratio 0.81, 95% confidence interval 0.72 to 0.93) and myocardial infarction (0.72, 0.61 to 0.85), with these estimates largely informed by cardiovascular outcome trials in high risk populations.
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979217
07HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, subcutaneous semaglutide was the only drug associated with reduced myocardial infarction (risk ratio 0.72).
In plain wordsIn adults with overweight or obesity, injected semaglutide was the only drug linked to fewer heart attacks.
Peptide
Semaglutide
Outcome
DecreaseMyocardial infarction
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
Risk ratio myocardial infarction
0.72
subcutaneous semaglutide
Source sentences
Summary
Subcutaneous semaglutide was the only drug associated with reduced all cause mortality (risk ratio 0.81, 95% confidence interval 0.72 to 0.93) and myocardial infarction (0.72, 0.61 to 0.85), with these estimates largely informed by cardiovascular outcome trials in high risk populations.
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979218
08HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, subcutaneous semaglutide reduced heart failure risk (risk ratio 0.43).
In plain wordsIn adults with overweight or obesity, injected semaglutide lowered the risk of heart failure.
Peptide
Semaglutide
Outcome
DecreaseHeart failure risk
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
Risk ratio heart failure
0.43
subcutaneous semaglutide
Source sentences
Summary
Subcutaneous semaglutide (0.43, 0.21 to 0.84) and tirzepatide (0.49, 0.27 to 0.88) reduced heart failure risk.
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979219
09HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, tirzepatide reduced heart failure risk (risk ratio 0.49).
In plain wordsIn adults with overweight or obesity, tirzepatide lowered the risk of heart failure.
Peptide
Tirzepatide
Outcome
DecreaseHeart failure risk
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Risk ratio heart failure
0.49
tirzepatide
Source sentences
Summary
Subcutaneous semaglutide (0.43, 0.21 to 0.84) and tirzepatide (0.49, 0.27 to 0.88) reduced heart failure risk.
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979220
10HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, subcutaneous semaglutide showed larger weight reductions in longer trials.
In plain wordsIn adults with overweight or obesity, injected semaglutide gave bigger weight loss in longer trials.
Peptide
Semaglutide
Outcome
Not applicableWeight loss by trial duration
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
larger weight reductions in trials with longer duration (shown for subcutaneous semaglutide), subgroup analyses for drug dosages and key patient characteristics did not identify credible differences in relative effects of treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
Report a problemFND-4241979223
11HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, orforglipron had a weight-change mean difference of -9.9% versus lifestyle modification alone at one year.
In plain wordsIn adults with overweight or obesity, orforglipron reduced weight more than lifestyle modification alone at one year.
Peptide
Orforglipron
Outcome
DecreaseWeight loss at one year
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · one yearAs given in this study (human).
Measurements
Mean difference in body weight change vs lifestyle modification alone
−9.9%
orforglipron, at one year
95% CI of mean difference
−12.4 to −7.5%
orforglipron, at one year
Source sentences
Summary
orforglipron (-9.9%, -12.4% to -7.5%)
3 context sentences(design, population, supporting numbers)
Summary · context
Compared with lifestyle modification alone, at one year,
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
Report a problemFND-4241979224
12HumanSystematic reviewSafety outcome
In adults with overweight or obesity, orforglipron increased fatigue risk, with a risk ratio of 3.4 and 100 more cases per 1000.
In plain wordsIn adults with overweight or obesity, orforglipron increased fatigue risk.
Peptide
Orforglipron
Outcome
IncreaseFatigue
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · one yearAs given in this study (human).
Measurements
Risk ratio, fatigue
3.4 risk ratio
orforglipron
Absolute increase in fatigue
100 more per 1000 people
orforglipron, over one year
Source sentences
Summary
Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year), orforglipron (3.4; 100 more per 1000), and CagriSema (3.2; 92 more per 1000).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
Report a problemFND-4241979227

Studies that did not test the peptide alone17

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.

13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, no drug in the pooled analysis, semaglutide included, convincingly improved quality of life beyond minimally important differences.
In plain wordsIn adults with overweight or obesity, none of the drugs studied together clearly improved quality of life by a meaningful amount.
Peptide
Semaglutide
Outcome
No significant changeQuality of life, pooled drugs
Study
n = 45,663
Outcome group
Quality of life · Whole body
Source sentences
Summary
No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979222
14HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, no studied drugs, including orforglipron, improved quality of life beyond established minimally important differences.
In plain wordsIn adults with overweight or obesity, no studied drugs improved quality of life beyond established meaningful differences.
Peptide
Orforglipron
Outcome
No significant changeQuality of life
Study
n = 45,663
Outcome group
Quality of life · Whole body
Measurements
Mean differences in quality of life, all drugs
< 5 points
all mean differences
Source sentences
Summary
No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
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.
Report a problemFND-4241979229
15HumanNot a test of Cagrilintide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, cagrilintide-semaglutide (CagriSema) produced substantial weight loss at one year compared with lifestyle modification alone, with moderate to high certainty evidence.
In plain wordsIn adults with overweight or obesity, CagriSema led to more weight loss at one year than lifestyle changes alone.
Peptide
Cagrilintide
Outcome
DecreaseWeight loss at one year with CagriSema
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference, weight change
−14.8%
CagriSema vs lifestyle modification at one year
Source sentences
Summary
cagrilintide-semaglutide (CagriSema, -14.8%, -16.9% to -12.7%)
2 context sentences(design, population, supporting numbers)
Summary · context
Compared with lifestyle modification alone, at one year
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979201
16HumanNot a test of Mazdutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, mazdutide, grouped with ecnoglutide and retatrutide, may produce similar or greater weight reductions (13.1-14.6%; very low to low certainty evidence).
In plain wordsIn adults with overweight or obesity, mazdutide, grouped with two other new drugs, may give weight loss of 13.1-14.6%, but the evidence is weak.
Peptide
Mazdutide
Outcome
DecreaseWeight loss with mazdutide
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight reduction range for ecnoglutide, mazdutide, retatrutide
13.1 to 14.6%
emerging agents
Source sentences
Summary
Emerging agents (ecnoglutide, mazdutide, retatrutide) may produce similar or greater reductions (13.1-14.6%; very low to low certainty).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
In this study, Mazdutide 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 Mazdutide.
Report a problemFND-4241979202
17HumanNot a test of Retatrutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, retatrutide, grouped with ecnoglutide and mazdutide, may produce similar or greater weight reductions (13.1-14.6%; very low to low certainty evidence).
In plain wordsIn adults with overweight or obesity, retatrutide, grouped with two other new drugs, may give weight loss of 13.1-14.6%, but the evidence is weak.
Peptide
Retatrutide
Outcome
DecreaseWeight loss with retatrutide
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight reduction range for ecnoglutide, mazdutide, retatrutide
13.1 to 14.6%
emerging agents
Source sentences
Summary
Emerging agents (ecnoglutide, mazdutide, retatrutide) may produce similar or greater reductions (13.1-14.6%; very low to low certainty).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
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.
Report a problemFND-4241979203
18HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, discontinuation because of adverse events was among the highest with CagriSema (risk ratios from 1.9 to 4.2 across the listed drugs).
In plain wordsIn adults with overweight or obesity, more people stopped CagriSema because of side effects, among the highest of the drugs compared.
Peptide
Cagrilintide
Outcome
IncreaseDiscontinuation because of adverse events with CagriSema
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Measurements
Risk ratio range for discontinuation, listed drugs
1.9 to 4.2 ratio
orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, oral semaglutide
Source sentences
Summary
Moderate to high certainty evidence supports discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2); gastrointestinal events were most increased with naltrexon…
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979204
19HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, fatigue risk increased with CagriSema (risk ratio 3.2; 92 more per 1000).
In plain wordsIn adults with overweight or obesity, CagriSema was linked to more fatigue, about 92 more cases per 1000 people over one year.
Peptide
Cagrilintide
Outcome
IncreaseFatigue risk with CagriSema
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Measurements
Risk ratio, fatigue
3.2 ratio
CagriSema
Absolute increase in fatigue
92 per 1000
CagriSema
Source sentences
Summary
Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year)
2 context sentences(design, population, supporting numbers)
Summary · context
and CagriSema (3.2; 92 more per 1000).
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979205
20HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, the combination cagrilintide-semaglutide (CagriSema) reduced body weight at one year by a mean difference of -14.8% versus lifestyle modification alone.
In plain wordsIn adults with overweight or obesity, the CagriSema combination led to substantial weight loss at one year compared with lifestyle change alone.
Peptide
Semaglutide
Outcome
DecreaseWeight loss at one year (CagriSema)
Study
n: not reported in source
Comparator
Lifestyle modification alone
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference in weight
−14.8%
CagriSema vs lifestyle modification
Source sentences
Summary
cagrilintide-semaglutide (CagriSema, -14.8%, -16.9% to -12.7%)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979207
21HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, discontinuation because of adverse events was highest with a pool of drugs that includes oral semaglutide and CagriSema (risk ratios from 1.9 to 4.2).
In plain wordsIn adults with overweight or obesity, more people stopped because of side effects with a group of drugs that includes oral semaglutide and CagriSema.
Peptide
Semaglutide
Outcome
IncreaseDiscontinuation due to adverse events, pooled drugs
Study
n: not reported in source
Outcome group
Adverse events · Metabolic and weight
Measurements
Risk ratio for discontinuation
1.9 to 4.2
pooled highest-risk drugs
Source sentences
Summary
discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979210
22HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, discontinuation because of adverse events was highest with a pool of drugs that includes liraglutide (risk ratios from 1.9 to 4.2).
In plain wordsIn adults with overweight or obesity, more people stopped because of side effects with a group of drugs that includes liraglutide.
Peptide
Liraglutide
Outcome
IncreaseDiscontinuation due to adverse events, pooled drugs
Study
n: not reported in source
Outcome group
Adverse events · Metabolic and weight
Measurements
Risk ratio for discontinuation
1.9 to 4.2
pooled highest-risk drugs
Source sentences
Summary
discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2)
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
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.
Report a problemFND-4241979211
23HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, gastrointestinal events were most increased with a pool of drugs that includes oral semaglutide (risk ratios from 3.1 to 4.2).
In plain wordsIn adults with overweight or obesity, stomach and gut side effects were most common with a group of drugs that includes oral semaglutide.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal events, pooled drugs
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio for gastrointestinal events
3.1 to 4.2
pooled highest-risk drugs
Source sentences
Summary
gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979212
24HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, gastrointestinal events were most increased with a pool of drugs that includes tirzepatide (risk ratios from 3.1 to 4.2).
In plain wordsIn adults with overweight or obesity, stomach and gut side effects were most common with a group of drugs that includes tirzepatide.
Peptide
Tirzepatide
Outcome
IncreaseGastrointestinal events, pooled drugs
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio for gastrointestinal events
3.1 to 4.2
pooled highest-risk drugs
Source sentences
Summary
gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks.
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.
Report a problemFND-4241979213
25HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, the combination CagriSema increased fatigue risk (risk ratio 3.2; 92 more per 1000 over one year).
In plain wordsIn adults with overweight or obesity, the CagriSema combination raised the risk of fatigue.
Peptide
Semaglutide
Outcome
IncreaseFatigue (CagriSema)
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Measurements
Risk ratio for fatigue
3.2
CagriSema
Source sentences
Summary
Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year), orforglipron (3.4; 100 more per 1000), and CagriSema (3.2; 92 more per 1000).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979214
26HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, no drug in the pooled analysis, semaglutide included, convincingly reduced kidney failure.
In plain wordsIn adults with overweight or obesity, none of the drugs studied together clearly reduced kidney failure.
Peptide
Semaglutide
Outcome
No significant changeKidney failure, pooled drugs
Study
n: not reported in source
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10).
1 context sentence(design, population, supporting numbers)
Summary · context
This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 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-4241979221
27HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome
In adults with overweight or obesity, drugs including orforglipron had the highest adverse-event discontinuation risk, with drug-specific risk ratios ranging from 1.9 to 4.2.
In plain wordsIn adults with overweight or obesity, a drug group including orforglipron had the highest adverse-event discontinuation risk.
Peptide
Orforglipron
Outcome
IncreaseAdverse-event discontinuation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Measurements
Risk ratio range, discontinuation because of adverse events (orforglipron and five other drugs)
1.9 to 4.2 risk ratio
drug-specific range across the listed drugs
Source sentences
Summary
Moderate to high certainty evidence supports discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2);
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
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.
Report a problemFND-4241979225
28HumanNot a test of Orforglipron aloneSystematic reviewSafety outcome
In adults with overweight or obesity, drugs including orforglipron had the greatest gastrointestinal-event increases, with drug-specific risk ratios ranging from 3.1 to 4.2.
In plain wordsIn adults with overweight or obesity, a drug group including orforglipron had the greatest increases in gastrointestinal events.
Peptide
Orforglipron
Outcome
IncreaseGastrointestinal events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio range, gastrointestinal events (orforglipron and three other drugs)
3.1 to 4.2 risk ratio
drug-specific range across the listed drugs
Source sentences
Summary
gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
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.
Report a problemFND-4241979226
29HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, no studied drugs, including orforglipron, convincingly reduced kidney failure.
In plain wordsIn adults with overweight or obesity, no studied drugs convincingly reduced kidney failure.
Peptide
Orforglipron
Outcome
No significant changeKidney failure
Study
n: not reported in source
Outcome group
Kidney function · Kidney and urinary
Source sentences
Summary
No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.
Summary · context
Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.
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.
Report a problemFND-4241979228

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 32 to 49Current
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 31
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Versions 7 to 30
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
Versions 2 to 6
9 Oct 2026, 03:07 UTC
The same notice was added 5 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