Navigating retatrutide safety: comprehensive insights from systematic review and meta-analysis 10.55131/jphd/2026/240123

Abstract

Retatrutide, a triple agonist (GIP, GLP-1, glucagon receptors), has shown promise in glycaemic control and weight loss, but its safety profile has not been studied in earlier studies. This study aims to systematically evaluate the safety profile of retatrutide by analyzing the incidence and risk of treatment-emergent adverse events. Through a comprehensive review of existing literature, the study seeks to quantify the relative risk of adverse effects, to inform clinical decision-making and future research directions. A systematic literature review following PRISMA 2020 guidelines was conducted across PubMed, Google Scholar, and Science Direct, focusing on studies investigating retatrutide's safety, and we excluded other studies (systematic reviews, narrative reviews, meta-analyses, etc.). Adverse event data, including treatment-emergent adverse events, were pooled and analysed for frequency and risk estimation. A total of 1,331 studies were initially identified, and after applying stringent inclusion and exclusion criteria, four studies were included in this Meta-analysis. We found that retatrutide significantly increased the incidence of adverse events compared to placebo (RR 1.87; 1.25, 2.80; p=0.003), with gastrointestinal disturbances (Nausea, decreased appetite, vomiting, constipation, etc.) being the most common. No significant difference in serious adverse events was observed (RR 0.81; 0.36, 1.83; p=0.61). Adverse events of special interest, such as hypersensitivity and pancreatitis, were notably higher in the retatrutide group (RR 2.94; 1.85, 4.69; p<0.00001). Retatrutide is effective for glycemic control and weight loss, but it increases the incidence of treatment-emergent adverse events, especially gastrointestinal issues, hypersensitivity, and pancreatitis. While serious adverse events were not significantly higher, careful patient selection, dose titration, and monitoring are crucial for patients with GI disorders, hypersensitivity, hepatic disease, cardiac disease etc. Clinicians should assess risks, particularly in vulnerable patients. Future research should explore the long-term safety of retatrutide and compare it with other therapies to refine treatment strategies and improve clinical decision-making.