Evidence map›Paper›PMID 41787737›Full record

ReviewEndocrinology, diabetes & metabolism2026

Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled Trials.

Ayah Abulehia, Hazem Ayesh, Omar Ayesh, Doha Jaber, Thekrayat Asad, Adham Itbaisha, Hamzeh Abugharbieh, Raged Gharbia, Lila H Abu-Hilal, Barbara Gisella Carranza Leon

Abstract readNetwork Meta-AnalysisComparative StudyReview
In one paragraph

Review in Endocrinology, diabetes & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Ayah AbulehiaFaculty of Medicine, Al-Quds University, Jerusalem, Palestine.ORCID https://orcid.org/0009-0003-4670-5065
Hazem AyeshDeaconess Health System, Evansville, Indiana, USA.ORCID https://orcid.org/0000-0001-8231-705X
Omar AyeshDepartment of Medical Laboratory Sciences, Al-Aqsa University, Gaza, Palestine.
Doha JaberFaculty of Medicine, Al-Quds University, Jerusalem, Palestine.ORCID https://orcid.org/0009-0007-8047-5768
Thekrayat AsadFaculty of Medicine, Al-Quds University, Jerusalem, Palestine.
Adham ItbaishaFaculty of Medicine, Al-Quds University, Jerusalem, Palestine.
Hamzeh AbugharbiehDepartment of Internal Medicine, University of Toledo, Toledo, Ohio, USA.
Raged GharbiaDepartment of Internal Medicine, University Hospitals Geauge Medical Center, Chardon, Ohio, USA.
Lila H Abu-HilalFaculty of Medicine, Al-Quds University, Jerusalem, Palestine.
Barbara Gisella Carranza LeonDivision of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionGlucagon receptor agonists (GRAs) are an emerging class of therapies for obesity and type 2 diabetes, demonstrating encouraging metabolic and weight-reducing effects. Several investigational GRA-based agents, including retatrutide, cotadutide, mazdutide, and survodutide, have reported promising results across early and mid-phase clinical trials. This comprehensive meta-analysis evaluates the efficacy and safety of these agents in individuals with type 2 diabetes, overweight, or obesity.

methodsPubMed, Cochrane, Embase, and Scopus databases were systematically searched. Fourteen randomised controlled trials meeting the inclusion criteria were analysed using frequentist network meta-analysis. Random-effects models were applied to assess mean differences (MD) in weight change, both absolute and percent changes, HbA1c, adverse events, and discontinuation due to adverse events. Heterogeneity was quantified using the I

resultsRetatrutide demonstrated the greatest weight reduction versus placebo (MD -13.44 kg; 95% CI [-18.38, -8.51]), followed by survodutide (MD -10.74 kg; 95% CI [-15.68, -5.80]) and mazdutide (MD -6.47 kg; 95% CI [-10.71, -2.24]). Cotadutide showed the smallest and nonsignificant effect (MD -3.41 kg; 95% CI [-11.63, 4.81]). Regarding HbA1c reduction, retatrutide showed the largest effect, followed by survodutide, mazdutide, and cotadutide; however, only the effect of retatrutide reached statistical significance. In terms of safety, mazdutide demonstrated the most favourable tolerability profile, whereas retatrutide and cotadutide were associated with comparatively lower tolerability.

conclusionsRetatrutide and survodutide exhibit the most favourable efficacy profiles for obesity and T2DM, with acceptable safety. These findings support their potential clinical use and highlight the need for future head-to-head trials.

Indexed as

Diabetes Mellitus, Type 2Hypoglycemic AgentsObesityGlucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinHumansRandomized Controlled Trials as TopicReceptors, GlucagonTreatment OutcomeWeight LossGlucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinHypoglycemic AgentsReceptors, Glucagonbody weightdiabetesglucagon receptor agonistsHbA1cmetabolismobesity

Identifiers

PMID41787737
PMCPMC12963462

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.