The Impact of Sotagliflozin on Renal Function, Albuminuria, Blood Pressure, and Hematocrit in Adults With Type 1 Diabetes

Abstract

Objective: In people with type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular risk and progression of diabetic kidney disease. Our aim was to determine whether sotagliflozin (SOTA), a dual SGLT1i and SGLT2i, had favorable effects on clinical biomarkers suggestive of kidney protection in adults with type 1 diabetes.

Research design and methods: In this 52-week pooled analysis, 1,575 adults enrolled in the inTandem1 and inTandem2 trials were randomized to SOTA 200 mg, 400 mg, or placebo in addition to optimized insulin therapy. Changes in cardiorenal biomarkers were assessed.

Results: At 52 weeks, in response to SOTA 200 and 400 mg, the placebo-corrected least squares mean change from baseline in estimated glomerular filtration rate was -2.0 mL/min/1.73 m2 (P = 0.010) and -0.5 mL/min/1.73 m2 (P = 0.52), respectively. Systolic blood pressure difference was -2.9 and -3.6 mmHg (P < 0.0001 for both); diastolic blood pressure changed by -1.4 (P = 0.0033) and -1.6 mmHg (P = 0.0008). In participants with baseline urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, UACR decreased by 23.7% (P = 0.054) and 18.3% (P = 0.18) for SOTA 200 and SOTA 400 mg, respectively, versus placebo. Increases in serum albumin and hematocrit and reductions in uric acid were observed throughout 52 weeks with both SOTA doses.

Conclusions: SOTA was associated with short- and long-term renal hemodynamic changes, which were similar to those seen with SGLT2i in type 2 diabetes. Further investigation around cardiorenal effects of SOTA in people with type 1 diabetes is justified.

© 2019 by the American Diabetes Association.

Figures

Figure 1

eGFR change over time in overall population. LS mean (LSM) change from baseline (BL) vs. placebo at week 52 for SOTA 200 mg, −1.96 mL/min/1.73 m2 (95% CI −3.45, −0.47), P = 0.010, and SOTA 400 mg, −0.49 mL/min/1.73 m2 (−1.99, 1.00), P = 0.52.

Figure 2

UACR change over time in subgroup of participants with baseline (BL) albuminuria (UACR ≥30 mg/g). Percentage change from baseline vs. placebo based on geometric mean estimated from MMRM model. At week 52, SOTA 200 mg, −23.7% (95% CI −48.9, 1.5), P = 0.054, and SOTA 400 mg, −18.3% (−45.3, 8.7), P = 0.18.

Figure 3

Blood pressure change over time. A: Changes in SBP in overall population. LS mean (LSM) change from baseline (BL) vs. placebo at week 52 for SOTA 200 mg, −2.9 mmHg (95% CI −4.3, −1.6), P < 0.0001, and SOTA 400 mg, −3.6 mmHg (−5.0 to −2.3), P < 0.0001. B: Changes in SBP in subgroup of patients with baseline SBP ≥130 mmHg. LS mean change from baseline vs. placebo at week 52 for SOTA 200 mg, −3.4 mmHg (−6.2, −0.7), P = 0.016, and SOTA 400 mg, −3.2 mmHg (−6.0, −0.4), P = 0.024. C: Changes in DBP in overall population. LS mean change from baseline vs. placebo at week 52 for SOTA 200 mg, −1.4 mmHg (−2.3, −0.5), P = 0.0033, and SOTA 400 mg, −1.6 mmHg (−2.5, −0.7), P = 0.0008. D: Changes in DBP in subgroup of patients with baseline DBP ≥80 mmHg. LS mean change from baseline vs. placebo at week 52 for SOTA 200 mg, −2.3 mmHg (−3.9, −0.6), P = 0.0064, and SOTA 400 mg, −2.1 mmHg (−3.8, −0.4), P = 0.016.

Figure 4

A: Changes in hematocrit in overall population. B: Changes in serum albumin in overall population. C: Changes in uric acid in overall population. BL, baseline; LSM, LS mean.