GLP ‐1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta‐Analysis of RCTs

Vienghirun, J; Sawangjit, R; Suttiruksa, S; Chaiyakunapruk, N; Jinathongthai, P; Khunti, K; Lee, SWH

doi:10.1111/dom.70698

Obesity

GLP ‐1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta‐Analysis of Randomized Clinical Trials (RCTs)

Diabetes Obes MetabPublished 23 Mar 2026Systematic review and network meta-analysis of randomised trials

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Authors' conclusion

Tirzepatide and Semaglutide_SC are most effective for clinically meaningful weight loss. Optimal dosing and adherence remain essential in practice.

Study context

Population: Overweight or obese adults with and without T2D
Participants: 58,976 participants127 RCTs

Comparison: GLP-1 RAs and dual agonists vs placebo and each other
Outcome: ≥ 5% and ≥ 10% weight loss, weight change (absolute and percentage), adverse events
Follow-up: 24-52 weeks

Methodological detailsrandom-effects models, SUCRA rankings, PRISMA 2020, PubMed, Embase, Scopus, CENTRAL and trial registries searched through April 30, 2025

Random-effects models
SUCRA rankings
PRISMA 2020
PubMed, Embase, Scopus, CENTRAL and trial registries searched through April 30, 2025

Pooled result

As reported in the abstract

≥ 5% weight loss, T2D

Each group vs placeboRelative risk (95% CI)

Tirzepatide

7.17(4.38–11.73)

Semaglutide_SC

4.74(3.17–7.08)

Semaglutide_oral

2.85(1.78–4.58)

Further pooled results

Outcome	← Lower risk vs placebo ←→ Higher risk vs placebo →	RR (CI)
≥ 5% weight loss, non-T2DTirzepatidevs Placebo	0.050.21520	2.99 (1.20–7.44)
≥ 5% weight loss, non-T2DSemaglutide_SCvs Placebo	0.050.21520	2.75 (1.14–6.61)
≥ 10% weight loss, T2DTirzepatidevs Placebo	0.050.21520	14.34 (5.98–34.35)
≥ 10% weight loss, T2DSemaglutide_oralvs Placebo	0.050.21520	6.86 (2.63–17.90)
≥ 10% weight loss, T2DSemaglutide_SCvs Placebo	0.050.21520	6.12 (2.97–12.59)
≥ 10% weight loss, non-T2DSemaglutide_SCvs Placebo	0.050.21520	10.72 (3.29–34.90)
≥ 10% weight loss, non-T2DTirzepatidevs Placebo	0.050.21520	4.70 (1.02–21.73)
	0.050.21520Relative risk (log scale)

Outcome	← Lower with tirzepatide ←→ Higher with tirzepatide →	MD (%) (CI)
Weight change (mixed treatment effects)Tirzepatidevs Semaglutide_oralT2D · direct head to head and indirect comparisons	−30−20−10010	−6.75 (−8.34 to −5.17)
Weight change (mixed treatment effects)Tirzepatidevs Semaglutide_SCT2D · direct head to head and indirect comparisons	−30−20−10010	−4.94 (−6.35 to −3.52)
Weight change (mixed treatment effects)Tirzepatidevs Placebonon-T2D; only effective agent · direct head to head and indirect comparisons	−30−20−10010	−16.48 (−21.70 to −11.27)
	−30−20−10010Difference, % (linear scale)

≥ 5% weight loss, non-T2D

Only tirzepatide and Semaglutide_SC were effective in non-T2D

Weight change (mixed treatment effects)

Higher doses enhanced weight loss

Safety

Outcome	← Lower risk with tirzepatide ←→ Higher risk with tirzepatide →	RR (CI)
Nausea/vomitingTirzepatidevs PlaceboMore common with tirzepatide	0.20.5125	3.64 (2.40–5.52)
	0.20.5125Relative risk (log scale)

Original publication

GLP ‐1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta‐Analysis of RCTs. Diabetes Obes Metab. Published 23 March 2026. doi:10.1111/dom.70698

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