Efficacy and safety of SGLT-2i in overweight/obese, non-diabetic individuals: a meta-analysis of randomized controlled trials

Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has been shown to decrease blood glucose levels in type 2 diabetes mellitus (T2DM) patients and potentially yield additional benefits in weight loss. This meta-analysis aimed to investigate the efficacy and safety of giving SGLT-2i to overweight/obese, non-diabetic individuals. Material and methods: The search was underpinned by PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Springer to identify English-language papers on randomized controlled trials (RCfs) on the use of SGLT-2i in overweight/obese, nondiabetic individuals published in and before March 2021, to study its effectiveness and safety. Results were evaluated by weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence interval (CI). Results: We reviewed 13 papers and compared the SGLT-2i group with the control group (other drugs and placebo) and found that SGLT-2i reduced weight (WMD = -1.33, p = 0.002) and waist circumference (WMD = -1.94, p = 0.03) in overweight/obese, non-diabetic individuals. The use of SGLT-2i is more effective than other interventions in terms of weight loss >= 5% (RR = 2.04, p < 0.001), but not in terms of weight loss >= 10% (RR = 1.133, p = 0.22). In addition, there were no significant changes in other metabolic parameters, like fasting plasma glucose (FPG), lipids, blood pressure, etc. SGLT-2i increased the risk of infections in urinary tract (RR = 1.91, p = 0.009) and reproductive system (RR= 4.09, p < 0.001). Conclusions: SGLT-2i is a promising candidate to reduce weight and waist circumference to a limited extent in overweight/obese, non-diabetic individuals. Generally, it is safe and effective. However, it potentially increased the risk of urogenital infections, which cannot be ignored.