Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials.

Hamarsheh S, Jaber AR, Abu-Khazneh O, Andonie CR, Majadleh S, Zahran A, Ayesh H

Endocrinology, diabetes & metabolism1 Jul 2026Cited by 2 (Europe PMC)

PMID42207966PMCIDPMC13239642DOI10.1002/edm2.70248PepBankPUB-42207966

Summary

BackgroundObesity is a chronic, progressive disease affecting over 1 billion adults worldwide, linked to serious comorbidities, including diabetes, hypertension, and cardiovascular disease and associated with increased mortality. Achieving clinically meaningful weight loss is critical to reducing cardiometabolic risk. Tirzepatide, semaglutide, cagrilintide and their combination (CagriSema) have demonstrated efficacy in clinical trials; however, no direct head-to-head studies have compared all advanced anti-obesity medications. This network meta-analysis examines their comparative efficacy and safety.MethodsWe systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity. Outcomes included changes in percent body weight, absolute weight, waist circumference, BMI, patients achieving ≥ 5% to ≥ 20% weight loss, HDL-C and safety outcomes (AEs, serious AEs, gastrointestinal AEs and treatment discontinuation). Random-effects model and network meta-analysis methods were employed.ResultsTwenty-five trials involving 12 interventions met the inclusion criteria. Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%). At the ≥ 20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70). Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09). Serious adverse events remained comparable to placebo across all regimens.ConclusionTirzepatide 15 mg and CagriSema achieve the greatest weight reduction, including ≥ 20% body weight loss. Gastrointestinal adverse events rise with treatment intensity, while serious adverse events remain comparable to placebo. These findings support dual-pathway and combination incretin therapies as preferred options for patients requiring substantial weight loss. Treatment selection should be individualized based on comorbidity burden, tolerability and weight loss goals, recognizing that ≥ 5% weight loss improves metabolic parameters while ≥ 10% is needed for meaningful comorbidity reduction. Future head-to-head trials are needed.

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

Results from this study14

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

01HumanSystematic reviewEfficacy outcome
In a network meta-analysis of adults with overweight or obesity, tirzepatide 15 mg gave the greatest percent weight reduction of 12 interventions versus placebo.
In plain wordsIn a combined analysis of trials in adults with overweight or obesity, tirzepatide 15 mg led to the largest weight loss versus placebo.
Peptide
Tirzepatide
Outcome
DecreasePercent weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Measurements
Mean difference
−17.97%
tirzepatide 15 mg
Source sentences
Summary
Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
Show in the study text Report a problemFND-4220796605
02HumanSystematic reviewEfficacy outcome
In a network meta-analysis of adults with overweight or obesity, semaglutide 7.2 mg reduced body weight by a mean difference of 14.66% versus placebo.
In plain wordsIn a combined analysis of trials in adults with overweight or obesity, semaglutide 7.2 mg led to weight loss versus placebo.
Peptide
Semaglutide
Outcome
DecreasePercent weight reduction
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
7.2 mgAs given in this study (human).
Measurements
Mean difference
−14.66%
semaglutide 7.2 mg
Source sentences
Summary
Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
Show in the study text Report a problemFND-4220796606
03HumanSystematic reviewEfficacy outcome
In a network meta-analysis of adults with overweight or obesity, tirzepatide 15 mg raised the chance of at least 20% weight loss versus placebo.
In plain wordsIn combined trials, tirzepatide 15 mg made 20% or more weight loss far more likely than placebo.
Peptide
Tirzepatide
Outcome
IncreaseWeight loss of 20% or more
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Measurements
Risk ratio
23.7 RR
tirzepatide 15 mg, weight loss >=20%
Source sentences
Summary
At the ≥ 20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
Show in the study text Report a problemFND-4220796608
04HumanSystematic reviewSafety outcome
In a network meta-analysis of adults with overweight or obesity, treatment discontinuation was highest with semaglutide 7.2 mg versus placebo.
In plain wordsIn a combined analysis of trials, more people stopped treatment with semaglutide 7.2 mg than with any other regimen, compared with placebo.
Peptide
Semaglutide
Outcome
IncreaseTreatment discontinuation
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
7.2 mgAs given in this study (human).
Measurements
Risk ratio
3.09 RR
discontinuation, semaglutide 7.2 mg
Source sentences
Summary
Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
Show in the study text Report a problemFND-4220796612

Studies that did not test the peptide alone10

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 a network meta-analysis of randomized trials in adults with overweight or obesity, CagriSema lowered percent body weight versus placebo (MD -17.84%).
In plain wordsIn adults with overweight or obesity, CagriSema led to large weight loss compared with placebo in a pooled analysis of trials.
Peptide
Cagrilintide
Outcome
DecreasePercent body weight change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference in percent body weight
−17.84%
CagriSema
Source sentences
Summary
followed by CagriSema (MD -17.84%)
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
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.
Show in the study text Report a problemFND-4220796601
06HumanNot a test of Cagrilintide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, CagriSema made weight loss of 20% or more far more likely than placebo (RR 27.82).
In plain wordsIn adults with overweight or obesity, many more people on CagriSema lost at least 20% of body weight than on placebo.
Peptide
Cagrilintide
Outcome
IncreaseWeight loss of 20% or more
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Risk ratio, weight loss of at least 20%
27.82 RR
CagriSema
Source sentences
Summary
CagriSema demonstrated marked superiority (RR 27.82)
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
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.
Show in the study text Report a problemFND-4220796602
07HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, gastrointestinal adverse events increased with all treatments, including CagriSema (RR 1.33-1.91), versus placebo.
In plain wordsIn adults with overweight or obesity, stomach and bowel side effects were more common with all the treatments, including CagriSema, than with placebo.
Peptide
Cagrilintide
Outcome
IncreaseGastrointestinal adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio, gastrointestinal adverse events
1.33 to 1.91 RR
all treatments
Source sentences
Summary
Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91)
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
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.
Show in the study text Report a problemFND-4220796603
08HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity, serious adverse events with all regimens, including CagriSema, were comparable to placebo.
In plain wordsIn adults with overweight or obesity, serious side effects were about as common with the treatments, including CagriSema, as with placebo.
Peptide
Cagrilintide
Outcome
No significant changeSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
Serious adverse events remained comparable to placebo across all regimens.
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
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.
Show in the study text Report a problemFND-4220796604
09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with overweight or obesity, CagriSema (semaglutide plus cagrilintide) reduced body weight by a mean difference of 17.84% versus placebo.
In plain wordsIn a combined analysis of trials in adults with overweight or obesity, the CagriSema combination led to large weight loss versus placebo.
Peptide
Semaglutide
Outcome
DecreasePercent weight reduction with CagriSema
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference
−17.84%
CagriSema
Source sentences
Summary
Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796607
10HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with overweight or obesity, CagriSema (semaglutide plus cagrilintide) showed the highest chance of at least 20% weight loss versus placebo.
In plain wordsIn combined trials, the CagriSema combination made 20% or more weight loss far more likely than placebo.
Peptide
Semaglutide
Outcome
IncreaseWeight loss of 20% or more with CagriSema
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Measurements
Risk ratio
27.82 RR
CagriSema, weight loss >=20%
Source sentences
Summary
At the ≥ 20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796609
11HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In a network meta-analysis of adults with overweight or obesity, gastrointestinal adverse events increased with all treatments, semaglutide included, versus placebo.
In plain wordsIn a combined analysis of trials, stomach and gut side effects rose with all the weight-loss drugs studied, semaglutide included, versus placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events (all treatments)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
1.33 to 1.91 RR
GI adverse events, all treatments
Source sentences
Summary
Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796610
12HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In a network meta-analysis of adults with overweight or obesity, gastrointestinal adverse events increased with all treatments, tirzepatide included, versus placebo.
In plain wordsIn a combined analysis of trials, stomach and gut side effects rose with all the weight-loss drugs studied, tirzepatide included, versus placebo.
Peptide
Tirzepatide
Outcome
IncreaseGastrointestinal adverse events (all treatments)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Risk ratio
1.33 to 1.91 RR
GI adverse events, all treatments
Source sentences
Summary
Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09).
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796611
13HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In a network meta-analysis of adults with overweight or obesity, serious adverse events remained comparable to placebo across all regimens, semaglutide included.
In plain wordsIn a combined analysis of trials, serious side effects were similar to placebo across all regimens, semaglutide included.
Peptide
Semaglutide
Outcome
No significant changeSerious adverse events (all regimens)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
Serious adverse events remained comparable to placebo across all regimens.
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796613
14HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In a network meta-analysis of adults with overweight or obesity, serious adverse events remained comparable to placebo across all regimens, tirzepatide included.
In plain wordsIn a combined analysis of trials, serious side effects were similar to placebo across all regimens, tirzepatide included.
Peptide
Tirzepatide
Outcome
No significant changeSerious adverse events (all regimens)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Source sentences
Summary
Serious adverse events remained comparable to placebo across all regimens.
2 context sentences(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity.
Summary · context
Twenty-five trials involving 12 interventions met the inclusion criteria.
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-4220796614

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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 4 to 39Current
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 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
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials.

Summary

Results from this study14

Studies that did not test the peptide alone10

Version history

Subjects

Publication types

MeSH terms