7792 Efficacy of Retatrutide for Weight Reduction and Its Cardiometabolic Effects Among Adults: A Systematic Review and Meta-Analysis

Abstract

Abstract Disclosure: D.C. Lopez: None. J.T. Pajimna: None. M.D. Milan: None. G.V. Jasul: None. G. Orpilla: None. I. Zapanta: None. B. Serquiña: None. G. Dychiao: None. Background: Obesity remains to be a global health challenge and it is associated with several complications such as diabetes, cardiovascular disease, fatty liver disease, and reduced life expectancy. Although lifestyle modifications are the mainstay for weight management, long term maintenance of weight loss can be a challenge for many affected adults. There have been proven safe and effective pharmacologic interventions but these remain limited to date. One of the novel anti-obesity drugs, retatrutide, is a single peptide with agonist activity at the GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of this triple-hormone receptor agonist, Retatrutide, in weight reduction and assess its cardiometabolic effects in adults. Methodology: An extensive electronic database search was done to identify studies published from inception until December 2023. All randomized controlled trials (RCT) that evaluated the use of retatrutide for adult patients were included. The Cochrane Risk of Bias 2.0 tool was used to assess the risk of bias of each study. Meta-analysis was conducted to determine weight reduction and glycemic control using random effects model which was reported at 95% confidence interval. Statistical heterogeneity was assessed using I2 statistics and random effects analysis and sensitivity analysis were done to control for the heterogeneity. Results: A total of 3 eligible RCTs were included in the study, all of which had risk of bias ranging from low to unclear. Of these articles, in 2 RCTs involving 353 participants with type 2 diabetes mellitus, retatrutide showed significant weight reduction by 11.89kg as compared to placebo (MD -11.89; 95% CI -13.53 to -10.25) and decreased glycosylated hemoglobin (HbA1C) by 1.64% as compared to placebo (MD: -1.64%, 95% CI [-2.38, -0.89]). Using direct comparison, retatrutide 12mg reduced body weight by 11.83kg as compared to dulaglutide 1.5mg with significant difference (MD -11.83; 95% CI -18.50 to -5.16), and retatrutide showed slight decrease in HbA1C by 0.61% as compared to dulaglutide (MD -0.66; 95% CI -0.66 to -0.56). In another 1 RCT involving 338 non-diabetic adult patients with obesity, retatrutide decreased least-squares mean percentage in body weight by 24.2% and 83% of participants who received retatrutide achieved weight reduction of 15% or more at 48 weeks. Conclusion: The use of retatrutide may result in substantial reductions in mean body weight and HbA1C as compared to controls in adult patients, with low to moderate certainty of evidence. In addition, retatrutide showed marked decrease in body weight but with modest glucose lowering effect when compared to a single GLP1 agonist drug. Presentation: 6/3/2024