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.
Abdrabou Abouelmagd. Alaa A; Abdelrehim. Amro Mamdouh AM; Bashir. Mohamed Nabih MN; Abdelsalam. Fares F; Marey. Ahmed A; Tanas. Yousef Y; Abuklish. Duha Milad DM; Belal. Mohamed Mohamed MM
Key Findings
- Average weight loss of 14.3% versus placebo.
- Reductions in BMI (‑5.38), waist circumference (‑10.5 cm), fasting glucose (‑23.5 mg/dL), HbA1c (‑0.91%), and systolic/diastolic BP (‑9.9/‑3.9 mm Hg).
- No significant increase in adverse events (RR = 1.11, p = 0.24).
Practical Outcomes
- Retatrutide shows strong potential as a weight‑loss and metabolic‑health tool, suggesting it could become a core part of future biohacking protocols once approved. Doses of 4‑12 mg were studied, with higher doses giving bigger effects. For now, enthusiasts should watch for upcoming large‑scale trials and regulatory updates before considering it.
Summary
A new drug called retatrutide, which hits three hormone receptors (GLP‑1, GIP, and glucagon), cut body weight by about 14% and improved blood sugar, blood pressure, and waist size in obese adults, with side‑effects similar to a placebo.
Abstract
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. 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). 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 <i>P</i> values < 0.00001. No significant difference in adverse events was observed between the groups (relative risk: 1.11, <i>P</i> = 0.24). 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.
Study Information
pubmed
2025
2025-02-05T00:00:00.000Z
10.1080/08998280.2025.2456441
6
34