ORIGINAL ARTICLE OPEN ACCESS Journal of the College of Physicians and Surgeons Pakistan 2023, Vol. 33(03): 308-313 308 Comparison of the Impact of SGLT2-Inhibitors and Exenatide on Body Fat Composition Esma Agcakaya 1 , Hacer Hicran Mutlu 1 , Ayse Erbakan 2 and Mehmet Sargin 1 1 Department of Family Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey 2 Division of Internal Medicine, Goztepe Prof Dr Suleyman Yalcin City Hospital, Istanbul, Turkey ABSTRACT Objective: To investigate the effect of SGLT2-i and GLP-1RA as an add-on therapy to metformin on weight loss and body composi- tion, and to compare their effects on glucose and lipid parameters. Study Design: A descriptive study. Place and Duration of the Study: Goztepe Prof Dr Suleyman Yalcin City Hospital, from January 2016 to May 2021. Methodology: The study included 50 patients with diabetes on metformin+SGLT2-i (dapagliflozin or empagliflozin, group 1) and 50 patients with diabetes on metformin+GLP-1 receptor agonist (RA, exenatide, group 2). Results: The reduction in weight, BMI, total body, abdominal, leg, and arm fat percentage, and the improvement in body fat-free and muscle mass percentage were significantly higher in Group 2 (p<0.001, p<0.001, p=0.014; p=0.031, p<0.001; p=0.002 and p=0.014, p=0.014, respectively). The decline in abdominal fat mass in the GLP-1 RA group was also significant (p=0.031). There was a significant decrease in HbA1c, fasting glucose, and triglyceride levels (p<0.001, p<0.001, and p=0.036) with a significant increase in HDL-C (p=0.015). There was no significant difference between groups for glucose, HbA1c, and lipid parameters (p>0.05). Conclusion: Both SGLT2 inhibitors and exenatide, when added to metformin therapy, were effective in reducing weight and body fat, more by the GLP-agonist. SGLT2-i had no significant impact on decreasing abdominal fat depicting that these agents do not have any benefit in treating visceral adiposity. Key Words: Type 2 diabetes mellitus, Obesity, GLP-1 receptor, SGLT2 inhibitor, Body fat distribution, Visceral adiposity. How to cite this article: Agcakaya E, Mutlu HH, Erbakan A, Sargin M. Comparison of the Impact of SGLT2-Inhibitors and Exenatide on Body Fat Composition. J Coll Physicians Surg Pak 2023; 33(03):308-313. INTRODUCTION Approximately 82.5% of individuals with type 2 diabetes mell- itus(DM)areobese,leadingtothename“diabesity”. 1 A5-10% weight loss results in improved glycaemic control and signifi- cant reductions in cardiovascular risk in patients with diabetes. 2 The emerging epidemic of 'diabesity’ raises the question of whether weight management and diabetes should be targeted as combined treatment strategies. 3 Currently, most guidelines recommend preferring the use of antidiabetic drugs with weight loss effects in the treatment of type 2 diabetes. 1 GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibi- tors (SGLT2-i) are glucose-lowering medications particularly recommended when there is a compelling need to reduce weightandalsocardiovascularriskindiabeticpeople. 4,5 Correspondence to: Dr. Hacer Hicran Mutlu, Department of Family Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey E-mail: hicranbeyca@hotmail.com ..................................................... Received: November 25, 2022; Revised: January 18, 2023; Accepted: February 07, 2023 DOI: https://doi.org/10.29271/jcpsp.2023.03.308 The antidiabetic drugs leading to weight loss are SGLT2-i and GLP-1RA. Sodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion by inhibiting renal glucose reabsorption by SGLT2, providing both glycaemic control and weight loss by developing a negative energy balance 6 and leadingtoa1-5Kgweightlossandreductioninfatmass. 5 Gluca- gon-like peptide-1 (GLP-1) is a peptide secreted from L cells in the small and large intestines. Glucagon-like receptor agonists (GLP-1 RAs), which have a potent incretin effect, lower glucose by enhancing insulin secretion and inhibiting glucagon secre- tion. 7 Besides, GLP-1RA induces weight loss by stimulating the satiety centre in the brain and slowing gastrointestinal motility. 8 Exenatide,asyntheticversionofexendin-4,isaGLP-1RA. 9 Even though, the United States Food and Drug Administration (US FDA)hasnotapprovedexenatideforthetreatmentofobesity,a meanof2-5Kgweightloss,mainlyasaresultofdecreasedbody fat mass, has been laid out in various studies. 9,10 ResearchontheSGLT2-iandGLP-1RAeffectonweightlosswith the change in body composition is limited and concluded with conflicting results. 9,11-15 Furthermore, no research has been foundthatcomparedtheeffectofSGLT2-iandGLP1-RAsoncea day as an add-on treatment to metformin on weight loss and change in body composition. The main objective of the study was to explore the effect of SGLT2-i (dapagliflozin 10 mg or