Clinical Pearls & Morning Reports
The incidence of type 1 diabetes, which currently affects 29 million adults worldwide, is rising. In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone, yet no oral medication has been approved for use in combination with insulin to lower the glucose level in patients with type 1 diabetes. Garg et al. conducted the inTandem3 trial, a phase 3 clinical trial that assessed the effects of sotagliflozin as compared with placebo with respect to glycemic control and the occurrence of severe hypoglycemia and diabetic ketoacidosis among adults with type 1 diabetes who were receiving their usual insulin therapy. Read the latest NEJM Original Article.
Q: What percentage of adults with type 1 diabetes achieve a glycated hemoglobin level lower than 7%?
A: Less than one third of adults with type 1 diabetes achieve a glycated hemoglobin level lower than 7.0%, and most are overweight or obese.
Q: What is sotagliflozin?
A: Sotagliflozin is a new oral inhibitor of sodium–glucose cotransporters 1 and 2 (SGLT1 and SGLT2). SGLT1 inhibition reduces glucose absorption in the proximal intestine, which significantly blunts and delays postprandial hyperglycemia. SGLT2 inhibition decreases renal glucose reabsorption. In phase 2 studies, the administration of sotagliflozin improved glycemic control and lowered body weight among patients with type 1 or 2 diabetes; it also reduced glycemia, despite a decreased bolus dose of insulin, among patients with type 1 diabetes.
A: In the trial by Garg et al., 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) were randomly assigned to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%]). The estimated between-group difference was 13.4 percentage points (95% confidence interval [CI], 9.0 to 17.8; P<0.001). The use of sotagliflozin was also associated with significant decreases in glycated hemoglobin level, fasting plasma glucose level, insulin dose, weight, and systolic blood pressure. However, among patients who had a glycated hemoglobin level of 7.0% or higher at week 24, the rate of diabetic ketoacidosis was significantly higher and the rate of severe hypoglycemia was nonsignificantly higher in the sotagliflozin group than in the placebo group.
A: Gastrointestinal events (consistent with SGLT1 inhibition) and genital mycotic infections (consistent with SGLT2 inhibition) were more common in the sotagliflozin group than in the placebo group. Diarrhea occurred in 29 patients (4.1%) in the sotagliflozin group and in 16 (2.3%) in the placebo group, and it led to discontinuation in 3 patients (0.4%) in the sotagliflozin group and none in the placebo group. Genital mycotic infection occurred in 45 patients (6.4%) in the sotagliflozin group and in 15 (2.1%) in the placebo group, and it led to discontinuation in less than 1% of patients in each trial group.