MON-602 The Efficacy and Safety of Sodium-Glucose Transport Protein 2 (SGLT-2) Inhibitors for Weight Loss Among Individuals Without Diabetes: A Systematic Review and Meta-Analysis

Background With the growing prevalence of obesity and its associated metabolic consequences, new strategies for safe and effective weight loss are called for. SGLT2i is a class oral antidiabetic agents that lowers glucose levels through renal glucose loss, with weight reduction as a consequence. Hence, its role in diabetes and obesity is well-recognized. However, its use among individuals without diabetes for safe and durable weight loss has not yet been sufficiently evaluated, although initial studies are promising. Objective To determine the efficacy and safety of SGLT2i compared to placebo among subjects without diabetes mellitus in terms of weight loss and adverse effects. Methods A meta-analysis was conducted on randomized controlled trials (RCTs) comparing different SGLT2i and placebo among patients without diabetes mellitus using RevMan 5.3 software. Results Five trials involving 779 patients met the eligibility criteria. SGLT2i used in these studies include Canagliflozin, Dapagliflozin, Sergliflozin and Remogliflozin with treatment duration ranging from 2 to 26 weeks. Pooled data of these 5 trials showed a significant difference in weight loss among subjects given SGLT2i (MD -1.34 kg [95% CI -1.51, -1.17]; p < 0.00001, I(2) = 0%) as compared to placebo. Four studies reported change in BMI as an outcome measure, likewise showing a significant difference favoring the use of SGLT2i (MD -0.50 [95% CI -0.56, -0.44]; p < 0.0001, I(2) = 0%). Two RCTs reported the percentage of weight loss. There was a significantly higher proportion of subjects achieving >5% weight loss among those given SGLT2i (RR 1.61 [95% CI 1.09, 2.38]; p = 0.02, I(2) = 0%). There was no significant difference in the proportion of subjects who achieved >10% weight loss (RR 1.42 [95% CI 0.60, 3.33]; p = 0.42, I(2) = 12%). Urogenital infections were more common in the SGLT2i group (RR 2.62 [95% CI 1.76, 3.91], p < 0.00001, I(2) = 0%) as reported in 4 studies. Only one study reported occurrence of hypoglycemia which did not differ significantly between both groups. Conclusion Although this meta-analysis shows a statistically significant decrease in weight (-1.34 kg, [95% CI -1.51, -1.17]) with the use of SGLT2i among subjects without diabetes, this might not be clinically relevant. With the increased risk of urogenital infections with its use, there is insufficient evidence to recommend its routine use as monotherapy for weight loss outside the population of individuals with diabetes. References Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs (2019) 79:219-230.