Type 1 Diabetes

First Dual SGLT Inhibitor May Have Cardiorenal Benefit in Type 1 Diabetes

The first oral dual sodium glucose cotransporter (SGLT) inhibitor sotagliflozin may confer beneficial short- and long-term renal hemodynamic changes similar to those observed with SGLT2 inhibitors in type 2 diabetes, suggest new findings published in Diabetes Care.

Sotagliflozin is intended as an adjunct to insulin therapy to lower hemoglobin A1c and improve renal outcomes in patients with type 1 diabetes, as 20% to 40% of these patients also have diabetic kidney disease, despite management of traditional renal risk factors. It was approved in Europe in April 2019 for certain adults with type 1 diabetes, but the US FDA decided against approving the therapy due to concerns for a small but increased risk for diabetic ketoacidosis. Researchers continue to assess sotagliflozin trial data due to the need for more therapies for patients with type 1 diabetes.

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In the present study, researchers assessed cardiorenal biomarker changes by performing pooled analysis of 52-week data from 1575 adults enrolled in the inTandem1 and inTandem2 trials. In these trials, patients were randomly assigned to treatment with 200 mg sotagliflozin, 400 mg sotagliflozin, or placebo, in addition to optimized insulin therapy.

The placebo-corrected least squares mean change in estimated glomerular filtration rate from baseline to 52 weeks was −2.0 mL/min/1.73 m2 and −0.5 mL/min/1.73 m2 in response to 200 mg and 400 mg sotagliflozin, respectively. Treatment with 200 mg and 400 mg sotagloflozin had resulted in systolic blood pressure differences of −2.9mm Hg and −3.6 mmHg, respectively, and diastolic blood pressure differences of −1.4 mmHg and −1.6 mmHg, respectively.

Among participants with a urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g at baseline, 200 mg and 400 mg sotagliflozin had resulted in a 23.7% and 18.3% decrease in UACR, respectively, compared with placebo. Both doses of sotagliflozin were also associated with increases in serum albumin and hematocrit levels, and reductions in uric acid throughout 52 weeks.

“While it is difficult to know whether these changes are similar or attenuated [vs] patients with type 2 diabetes in the absence of head-to-head trials, our data suggest that dual SGLT1 and SGLT2 inhibition has the potential to confer cardiorenal protection in ways analogous to selective SGLT2 inhibition in people with type 1 and type 2 diabetes,” the researchers wrote of their findings.

“Dedicated trials exploring renal and [cardiovascular] protective pathways are warranted in people with type 1 diabetes with preexisting cardiac or renal disease,” they added.

—Christina Vogt

van Raalte DH, Bjornstad P, Persson F, et al. The impact of sotagliflozin on renal function, albuminuria, blood pressure, and hematocrit in adults with type 1 diabetes. Diabetes Care. 2019;42(10):1921-1929.