Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial.

Autor: Baker C; Diabetes and Endocrine Associates, Omaha, Nebraska., Wason S; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas., Banks P; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas., Sawhney S; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas., Chang A; John Muir Physician Network, Concord, California., Danne T; Department of Diabetes, Endocrinology, and Clinical Research, Children's and Youth Hospital Auf der Bult, Hannover Medical School, Hannover, Germany., Gesty-Palmer D; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas., Kushner JA; McNair Interests & McNair Medical Institute, Houston, Texas., McGuire DK; Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas., Mikell F; Chief Physician Executive, Hospital Sisters Health System, Springfield, Illinois., O'Neill M; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas., Peters AL; Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California., Strumph P; Lexicon Pharmaceuticals, Inc., The Woodlands, Texas.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2019 Nov; Vol. 21 (11), pp. 2440-2449. Date of Electronic Publication: 2019 Aug 01.
DOI: 10.1111/dom.13825
Abstrakt: Aims: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D).
Materials and Methods: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE).
Results: From a mean baseline of 8.0% ± 0.8% (full study population), placebo-adjusted LSM HbA1c decreased by 0.3% (P = .07), 0.5% (P < .001) and 0.4% (P = .006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo-adjusted PPG decreased by 22.2 mg/dL (P = .28), 28.7 mg/dL (P = .16) and 50.2 mg/dL (P = .013), UGE increased by 41.8 g/d (P = .006), 57.7 g/d (P < .001) and 70.5 g/d (P < .001), and weight decreased by 1.3 kg (P = .038), 2.4 kg (P < .001) and 2.6 kg (P < .001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg.
Conclusions: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).
(© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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