Safety and efficacy of sotagliflozin in patients with type II diabetes mellitus and chronic kidney disease: a meta-analysis of randomized controlled trials

Abstract

Background: Sotagliflozin is a dual sodium-glucose co-transporter 1 and 2 inhibitor that increases glucosuria and natriuresis in patients with type 2 diabetes mellitus (T2DM). However, the safety and efficacy in patients with concomitant chronic kidney disease (CKD) remains unclear. Therefore, we aimed to conduct a meta-analysis to evaluate the current evidence in this regard.

Methods: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the safety and efficacy of Sotagliflozin in patients with T2DM and CKD compared with placebo. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I² statistics. The study was recorded in PROSPERO registry (CRD42023449631). RESULTS : We included three studies totaling 11,648 patients followed for 15.7 ± 5.9 months. Reduction in HbA₁C (mean difference - 0.33%; 95% CI [- 0.54, - 0.11]; p = 0.003; I² = 100%) and weight (mean difference - 1.01 kg; 95% CI [- 1.17, - 0.86]; p < 0.00001; I² = 96%) were significantly higher in the Sotagliflozin group compared with placebo. All-cause mortality (RR 0.98; 95% CI [0.81, 1.20]; p = 0.87; I² = 0%) and major adverse cardiovascular events (RR 0.70; 95% CI [0.40, 1.21]; p = 0.20; I² = 39%) were not significantly different between groups. However, estimated glomerular filtration rate reduction (mean difference - 0.95; 95% CI [- 1.32, - 0.58]; p < 0.00001; I² = 98%), genital mycotic infections (RR 2.73; 95% CI [1.96, 3.79]; p < 0.00001; I² = 0%), diarrhea (RR 1.42; 95% CI [1.24. 1.63]; p < 0.00001; I² = 0%) and volume depletion (RR 1.31; 95% CI [1.11, 1.56]; p = 0.002; I² = 0%) were more common with Sotagliflozin.

Conclusions: In patients with T2DM and CKD, Sotagliflozin appears to be effective for glycemic control and weight loss. Although the medication seemed safe concerning mortality and cardiovascular events, it induced estimated glomerular filtration rate reduction, and was associated with a higher risk of genital mycotic infections, diarrhea, and volume depletion.

Keywords: Chronic kidney disease; Sotaglifozin; Type 2 diabetes mellitus.