Retatrutide, a peptide that hits three gut hormone receptors, has been shown in several clinical trials to cause strong weight loss and better metabolic health when given as a weekly injection. The 12 mg dose worked best, helping people lose 5‑20% of their body weight, but it can cause stomach upset.

Obesity is a major public health issue linked to various health complications. Retatrutide, a triple agonist peptide targeting the glucagon receptor, GIP receptor, and GLP-1 receptor, shows promise in addressing this need. This systematic review assessed the safety and efficacy of retatrutide for obesity treatment using available clinical trial data. We conducted a comprehensive search of databases, including PubMed, Cochrane and ClinicalTrials.gov, from their inception until March 15, 2025 following PRISMA guidelines. Three articles were included in this systematic review, screening a total of 1,082 patients, with 691 randomly assigned to groups. The average age of participants was 54.26 ± 9.9 years, consisting of 335 men (48 %) and 356 women (52 %). Retatrutide was administered to 510 participants, while 130 received a placebo. The 12 mg dosage of retatrutide showed the most significant reductions in body weight, body mass index, and waist circumference. It also led to a higher percentage of patients achieving weight losses of ≥5 , 10, 15, and 20 %. Gastrointestinal adverse effects were the most commonly reported. Weekly subcutaneous injections of retatrutide in obese patients resulted in significant weight loss and metabolic improvements compared to a placebo.