Meta‐analysis of sotagliflozin, a dual sodium‐glucose‐cotransporter 1/2 inhibitor, for heart failure in type 2 diabetes

Abstract Sodium‐glucose co‐transporters (SGLTs) mediate sodium and glucose transport across cell membranes. SGLT2 inhibitors have a recognized place within heart failure (HF) guidelines. We evaluated the effect of sotagliflozin on HF and cardiovascular outcomes in participants with type 2 diabetes. Scopus, Medline, Embase and Central were searched from inception until 2 June 2023. Randomized controlled trials evaluating sotagliflozin in type 2 diabetes participants and reporting HF events were selected. Major adverse cardiovascular events (MACE) and systolic blood pressure were evaluated. The Cochrane risk of bias tool (RoB 2.0) was used. Pooled mean difference (MD), relative risk (RR), 95% confidence intervals and the number needed to treat (NNT) were estimated (PROSPERO: CRD42023432732). We selected nine studies ( n = 15 320 participants: n = 8040 intervention and n = 7280 control). The median follow‐up was 13.4 months (Q1 = 13, Q3 = 21). One study recruited participants with HF at baseline. After a follow‐up of >52 weeks, sotagliflozin significantly reduced the risk of HF [ n = 8 studies; RR = 0.66 (0.64, 0.69)], stroke [ n = 6 studies; RR = 0.75 (0.58, 0.97)] and MACE [ n = 8 studies; RR = 0.73 (0.66, 0.81)]. The NNT was 20 and 26 for HF and MACE, respectively. Sotagliflozin lowered systolic blood pressure [ n = 7; MD = −2.38 mmHg (−2.79, −1.97)]. No dose‐dependent effect was identified for HF [200 mg: RR = 0.38 (0.16, 0.89), 400 mg: RR = 0.57 (0.39, 0.85), P ‐value = 0.22]. The high risk of bias was a limitation of this review. Sotagliflozin reduced HF and cardiovascular events in type 2 diabetes participants. Research exploring its effects in HF and comparisons with SGLT2 inhibitors is warranted to determine if dual SGLT inhibition surpasses selective inhibition.