Abstract 4146166: Effect of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, on Systolic Blood Pressure in Patients with Type 2 Diabetes

Clinical trials (inTandem, SOLOIST-WHF, and SCORED) utilizing sotagliflozin (SOTA) have demonstrated glycemic improvements in patients with type 1 diabetes (T1D) and reduced heart failure (HF)-related events and cardiovascular (CV) mortality in patients with type 2 diabetes (T2D). SOTA has been evaluated for changes in cardiometabolic parameters including glycemia, blood pressure, and body weight in 8 double-blind, placebo (PBO)-controlled trials in patients with T2D. The glycemic efficacy of SGLTi including SOTA is attenuated with declining kidney function, but it is not known if the effects of SOTA on blood pressure are impacted as well. The purpose of this post-hoc, patient-level meta-analysis from the Phase 3 studies in patients with T2D was to determine the effect of SOTA on systolic blood pressure (SBP) across a broad range of patients including those with moderate to severe renal impairment. The participants (mean age 63 yrs, BMI 32 kg/m 2 , SBP 133 mmHg, eGFR 74 mL/min/1.73m 2 ) were treated with once-daily SOTA 400 mg (N=1728), SOTA 200 mg (N=728), or PBO (N=1440). Of the 3,896 participants, there were 2,207 patients with a SBP≥ 130 mmHg and 1,120 with a SBP≥ 140 mmHg at baseline despite the use of antihypertensive medications in 81% of patients as well as 271 patients with eGFR < 30, 1,046 with eGFR 30 to < 60, and 2,577 with eGFR ≥ 60 mL/min/1.73m 2 . At 26 weeks, SOTA 200mg and 400mg significantly (p≤ 0.05) reduced SBP in all patients compared to PBO, LS mean difference (95% confidence interval [CI]) -3.5 (-4.7, -2.3) and -3.4 (-4.3, -2.5), respectively, as well as significant reductions in subgroups of patients with SBP≥ 130 mmHg, -2.6 (-4.3, -1.0) and -3.7 (-4.9,-2.5), respectively, and SBP≥ 140 mmHg, -2.5 (-4.9, -0.1) and -3.6 (-5.6, -1.7), respectively. Moreover, reductions in SBP with SOTA were seen in patients regardless of baseline eGFR. (Figure) Despite the known attenuation of glycemic control with SGLTi with declining kidney function, the effects of SOTA on SBP are maintained in patients with T2D regardless of kidney function. Together with improvements in other cardiometabolic parameters shown in both patients with T1D and T2D, SOTA may offer a new therapeutic option for patients with diabetes.