Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.

Kamrul-Hasan ABM, Khalil I, Mahajan K, Dutta D, Banerjee M, Pappachan JM

Endocrinology, diabetes & metabolism1 May 2026

PMID42175595PMCIDPMC13240113DOI10.1002/edm2.70247PepBankPUB-42175595

Summary

BackgroundLong-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.MethodsWe conducted a frequentist random-effects NMA of randomized controlled trials comparing novel ABTs with placebo or active comparators in R. Primary outcome was the percent change in body weight from baseline. Secondary outcomes included absolute weight changes, anthropometric measures, and overall and specific GI adverse events (AEs). Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.ResultsSix trials (N = 4642; 12-68 weeks) were included. Compared with placebo, high dose (HiD) subcutaneous amycretin produced the largest reduction in percent body weight (mean difference -23.95%; P score 1.00), followed by HiD eloralintide (-18.01%; P score 0.89) and HiD CagriSema (-17.18%; P score 0.85), all exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). Almost similar patterns were observed for absolute weight, body mass index, waist circumference and categorical weight-loss thresholds. GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema, while diarrhoea mainly increased with semaglutide 2.4 mg. Only HiD CagriSema increased AE-related discontinuation.ConclusionsNovel ABTs, such as HiD amycretin, CagriSema and eloralintide, may induce substantial short- to medium-term weight loss but may also increase GI AEs; given sparse, low-certainty data, these findings are preliminary and require confirmation in larger trials.Trial registrationThe meta-analysis was registered in PROSPERO (CRD420261340457). The review protocol summary can be accessed at the PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261340457).

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

Results from this study11

3 results from studies that gave the peptide. 3 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, a network meta-analysis estimated that semaglutide 2.4 mg reduced percent body weight by 11.45% versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, semaglutide 2.4 mg lowered body weight by 11.45% more than placebo in a pooled analysis.
Peptide
Semaglutide
Outcome
DecreasePercent change in body weight, semaglutide 2.4 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mgAs given in this study (human).
Measurements
Mean difference, percent body weight
−11.45%
semaglutide 2.4 mg vs placebo
Source sentences
Summary
all exceeding semaglutide 2.4 mg (-11.45%)
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
Show in the study text Report a problemFND-4217559501
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, a network meta-analysis estimated that liraglutide 3.0 mg reduced percent body weight by 6.4% versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, liraglutide 3.0 mg lowered body weight by 6.4% more than placebo in a pooled analysis.
Peptide
Liraglutide
Outcome
DecreasePercent change in body weight, liraglutide 3.0 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
3.0 mgAs given in this study (human).
Measurements
Mean difference, percent body weight
−6.4%
liraglutide 3.0 mg vs placebo
Source sentences
Summary
liraglutide 3.0 mg (-6.4%)
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
Show in the study text Report a problemFND-4217559502
03HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, diarrhoea increased mainly with semaglutide 2.4 mg versus placebo in the network meta-analysis.
In plain wordsIn adults with overweight or obesity without diabetes, diarrhoea was more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseDiarrhoea, semaglutide 2.4 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mgAs given in this study (human).
Source sentences
Summary
while diarrhoea mainly increased with semaglutide 2.4 mg.
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
Show in the study text Report a problemFND-4217559509

Studies that did not test the peptide alone8

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.

04HumanNot a test of Cagrilintide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, a network meta-analysis estimated that high-dose CagriSema (cagrilintide with semaglutide) reduced percent body weight by 17.18% versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose CagriSema, a two-drug product, lowered body weight by 17.18% more than placebo in a pooled analysis.
Peptide
Cagrilintide
Outcome
DecreasePercent change in body weight, high-dose CagriSema
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference, percent body weight
−17.18%
HiD CagriSema vs placebo
Source sentences
Summary
HiD CagriSema (-17.18%; P score 0.85)
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559503
05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, a network meta-analysis estimated that high-dose CagriSema (cagrilintide with semaglutide) reduced percent body weight by 17.18% versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose CagriSema, a two-drug product, lowered body weight by 17.18% more than placebo in a pooled analysis.
Peptide
Semaglutide
Outcome
DecreasePercent change in body weight, high-dose CagriSema
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Measurements
Mean difference, percent body weight
−17.18%
HiD CagriSema vs placebo
Source sentences
Summary
HiD CagriSema (-17.18%; P score 0.85)
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559504
06HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, gastrointestinal adverse events were more common with high-dose amylin-based therapies, especially oral amycretin and CagriSema, than with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose amylin-based drugs, especially CagriSema, caused more stomach and bowel side effects than placebo.
Peptide
Cagrilintide
Outcome
IncreaseGastrointestinal adverse events, high-dose amylin-based therapies
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559505
07HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, nausea was more common with high-dose amylin-based therapies, especially oral amycretin and CagriSema, than with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose amylin-based drugs, especially CagriSema, caused more nausea than placebo.
Peptide
Cagrilintide
Outcome
IncreaseNausea, high-dose amylin-based therapies
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559506
08HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, vomiting was more common with high-dose amylin-based therapies, especially oral amycretin and CagriSema, than with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose amylin-based drugs, especially CagriSema, caused more vomiting than placebo.
Peptide
Cagrilintide
Outcome
IncreaseVomiting, high-dose amylin-based therapies
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559507
09HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, constipation was more common with high-dose amylin-based therapies, especially oral amycretin and CagriSema, than with placebo.
In plain wordsIn adults with overweight or obesity without diabetes, high-dose amylin-based drugs, especially CagriSema, caused more constipation than placebo.
Peptide
Cagrilintide
Outcome
IncreaseConstipation, high-dose amylin-based therapies
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559508
10HumanNot a test of Cagrilintide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, only high-dose CagriSema increased discontinuation due to adverse events versus placebo among the amylin-based therapies.
In plain wordsIn adults with overweight or obesity without diabetes, only high-dose CagriSema led to more stopping of treatment because of side effects than placebo.
Peptide
Cagrilintide
Outcome
IncreaseAdverse-event-related discontinuation, high-dose CagriSema
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Source sentences
Summary
Only HiD CagriSema increased AE-related discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559510
11HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, only high-dose CagriSema increased discontinuation due to adverse events versus placebo among the amylin-based therapies.
In plain wordsIn adults with overweight or obesity without diabetes, only high-dose CagriSema led to more stopping of treatment because of side effects than placebo.
Peptide
Semaglutide
Outcome
IncreaseAdverse-event-related discontinuation, high-dose CagriSema
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Whole body
Source sentences
Summary
Only HiD CagriSema increased AE-related discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.
Summary · context
Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores.
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-4217559511

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 5 to 6Current
27 Oct 2026, 16:32 UTC
The same notice was added 2 times, first on 21 Oct 2026, 12:50 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 4
10 Oct 2026, 10:21 UTC
Study results updated
Versions 2 to 3
9 Oct 2026, 03:06 UTC
The same notice was added 2 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

Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.

Summary

Results from this study11

Studies that did not test the peptide alone8

Version history

Subjects

Publication types

MeSH terms

Keywords