November 17, 2019
Improving Glycemic Control in Diabetes

Improving Glycemic Control in Diabetes


Insulin is the mainstay of treatment for patients
with type 1 diabetes mellitus. However, despite appropriate treatment, patients
often have inadequate glycemic control and remain at risk for life-threatening complications such as severe hypoglycemia and diabetic ketoacidosis. Sotagliflozin is an oral inhibitor of sodium-glucose cotransporters 1 and 2 (SGLT1 and SGLT2). SGLT1 is present mainly in the proximal intestine,
where its inhibition decreases glucose absorption and blunts postprandial hyperglycemia. In contrast, SGLT2 inhibition decreases renal
glucose absorption. InTandem3, a multicenter,
double-blind trial, tested whether the addition of sotagliflozin to insulin therapy would
improve glycemic control and reduce complication rates in patients with type 1 diabetes. After a 2-week run-in period on placebo, 699 adult patients were randomized to receive sotagliflozin and 703 to receive placebo for 24 weeks. The baseline mean glycated hemoglobin level
was 8.26% in the sotagliflozin group and 8.21% in the placebo group. At week 24, significantly more patients in
the sotagliflozin group than in the placebo group achieved the primary outcome, a glycated
hemoglobin level below 7% with no episodes of severe hypoglycemia or diabetic ketoacidosis, 28.6% vs. 15.2%. Patients randomized to sotagliflozin
also had improvement from baseline in glycated hemoglobin, weight, and systolic blood pressure. However, patients in the sotagliflozin group experienced had more serious adverse
events, including higher incidence of diabetic ketoacidosis . The authors conclude that among patients
with type 1 diabetes receiving insulin, the addition of sotagliflozin increased
the proportion with a glycated hemoglobin level below 7.0%, but also increased
the rate of diabetic ketoacidosis. Full trial results are available at NEJM.org.

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