In people with type 2 diabetes (T2D), SGLT2 inhibitors reduce cardiovascular risk and diabetic kidney disease (DKD) progression. Because several mechanisms of DKD progression overlap in people with T2D and T1D, our aim was to assess if sotagliflozin (SOTA), a dual SGLT1 and 2 inhibitor, had favorable renal effects suggestive of kidney protection in adults with T1D.

In this 52-week pooled analysis, 1575 adults enrolled in the InTandem 1 and 2 trials were randomized to SOTA 200 mg, 400 mg, or placebo (PBO) in addition to optimized insulin therapy. Mean changes of eGFR (MDRD), urinary albumin to creatinine ratio (UACR, geometric mean), systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to week 52 were compared with PBO.

From a baseline eGFR of 89.30±0.86 ml/min/1.73m2, mean eGFR reduction was -2.50±0.63 ml/min/1.73m2 vs. PBO after 4 weeks for SOTA 200 mg and similar change was observed with 400 mg (p<0.0001 for both). From week 4 to 52, although lower than PBO, eGFR tended to return toward baseline. At 52 weeks, eGFR was -1.96±0.76 (p=0.01) and -0.49±0.76 ml/min/1.73m2 (p=0.52) for SOTA 200 and 400 mg vs. PBO, respectively. In response to SOTA 200 and 400 mg, SBP decreased by -2.91±0.68 mmHg and -3.62±0.68 mmHg (p<0.001 vs. PBO for both); DBP decreased by -1.39±0.47 and -1.59±0.47 mmHg (p<0.01 vs. PBO for both). In adults with baseline microalbuminuria (n=156), SOTA 200 mg lowered UACR by 24.51±11.66% (p=0.03 vs. PBO), whereas changes in UACR with SOTA 400 mg did not differ vs. PBO. Increases in serum albumin and hematocrit at 12 weeks persisted at 52 weeks with both SOTA doses (p<0.01).

In adults with T1D, SOTA 200 mg was associated with short and long-term hemodynamic changes in eGFR and lower UACR. SOTA 200 and 400 mg lowered SBP and DBP and induced mild hemoconcentration. These data suggest that the renal hemodynamic profile of SOTA in T1D is similar to that seen with SGLT2 inhibition in T2D. Further investigation around cardiorenal effects of SOTA in people with T1D is warranted.

Disclosure

D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. R. Castro: Employee; Self; Sanofi US. S. Wang: Employee; Self; Sanofi US. D.R. Powell: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.

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