Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study

Diabetes Care. 2018 Sep;41(9):1970-1980. doi: 10.2337/dc18-0343. Epub 2018 Jun 24.

Abstract

Objective: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D).

Research design and methods: The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400 mg (n = 262) after 6 weeks of insulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks.

Results: From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P < 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were -1.08 mmol/L for fasting plasma glucose, -4.32 kg for weight, and -15.63% for bolus insulin dose and -11.87% for basal insulin dose (all P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo.

Conclusions: In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetic Ketoacidosis / epidemiology
  • Double-Blind Method
  • Drug Therapy, Combination / standards
  • Female
  • Glycated Hemoglobin A
  • Glycosides / administration & dosage*
  • Glycosides / adverse effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin Infusion Systems / standards
  • Male
  • Middle Aged
  • North America / epidemiology
  • Weight Loss / drug effects

Substances

  • Glycated Hemoglobin A
  • Glycosides
  • Insulin
  • (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Associated data

  • ClinicalTrials.gov/NCT02384941