Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without diabetes.

Methods: PubMed, Scopus, Web of Science, and Cochrane databases were searched from inception until May 2024. Eligible studies comprised randomized controlled trials that compared retatrutide with placebo in obese patients. We excluded studies on healthy populations, non-English texts, single-arm studies, animal studies, and abstracts. RevMan software (version 5.4) was used for analysis, with subgroup evaluation by dose (4 mg, 8 mg, 12 mg).

Results: Three randomized controlled trials, encompassing 878 patients, satisfied our inclusion criteria. Retatrutide significantly reduced body weight (mean difference [MD]: -14.33%), body mass index (MD: -5.38), waist circumference (MD: -10.51 cm), fasting plasma glucose (MD: -23.51 mg/dL), hemoglobin A1c (MD: -0.91%), and systolic and diastolic blood pressure (MD: -9.88 mm Hg and -3.88 mm Hg, respectively), all with P values < 0.00001. No significant difference in adverse events was observed between the groups (relative risk: 1.11, P = 0.24).

Conclusion: Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile. However, additional large and long-term trials are required to establish these results.

Keywords: GIP; GLP-1; glucagon; meta-analysis; obesity; retatrutide.

Figure 1.

PRISMA flow diagram.

Figure 2.

Risk of bias assessment.

Figure 3.

Forest plot of the percent weight reduction in different retatrutide doses.