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Body weight influences SGLT2-inhibitor effects in type 1 diabetes



– Individuals with type 1 diabetes and a high body mass index gain the most benefit with the least risk when sodium-glucose cotransporter 2 (SGLT2) inhibitors are added to insulin therapy, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

Dr. Thomas Dahne, Auf der Bult Hospital for Children and Adolescents, Hannover Medical School, Germany Sara Freeman/MDedge News

Dr. Thomas Danne

Results from new analyses of the inTandem 1 and inTandem 2 trials with sotagliflozin (Zynquista), and the DEPICT-1 and DEPICT-2 trials with dapagliflozin (Farxiga), support the recent decision of the European Medicines Agency to license the use of the drugs only in patients with a BMI of 27 kg/m2 or higher.

inTandem with sotagliflozin

Weight gain is a challenge in patients with type 1 diabetes, said Thomas Danne, MD, who presented post hoc data from the two inTandem studies. “It’s a little bit counterintuitive,” he acknowledged, “but you have to realize, particularly in patients who have hypoglycemia, that they have to take in extra carbohydrates,” which may tip them to becoming overweight or obese.

SGLT2-inhibitor therapy with sotagliflozin or dapagliflozin added to insulin therapy has been shown to reduce body weight in individuals with type 1 diabetes, but there is an increased risk for diabetic ketoacidosis (DKA). That risk, however, seems to be lower in the higher body-weight categories.

Dr. Danne, director of the department of general pediatrics, endocrinology, and diabetology, and clinical research at the Auf der Bult Hospital for Children and Adolescents, at the Hannover (Germany) Medical School, presented data looking at the outcomes of patients treated with sotagliflozin or placebo based on their BMI.

In all, 1,575 patients were included in the analysis, of whom 659 were of normal weight (BMI of less than 27 kg/m2; average mean, 24 kg/m2 at baseline), and 916 had a higher weight (BMI of 27 kg/m2 or higher; average mean, 32 kg/m2 at baseline). The mean age of patients at study entry was 42 years for those with the lower BMI, and 45 years for those with the higher BMI.

Patients in the two inTandem trials had been treated with insulin plus placebo (n = 228, BMI less than 27 kg/m2; n = 298, BMI 27 kg/m2 or higher), or insulin plus sotagliflozin at a dose of 200 mg (n = 219, BMI less than 27 kg/m2; n = 305, BMI 27 kg/m2 or higher) or 400 mg (n = 212; BMI less than 27 kg/m2; n = 313, BMI 27 kg/m2 or higher).

Glycemic control and body weight

Greater reductions in glycated hemoglobin (HbA1c) were seen with sotagliflozin versus placebo, and even more so, if the BMI was 27 kg/m2 or higher. At week 24, the least-squares mean difference in HbA1c comparing sotagliflozin 200 mg and placebo was –0.32 in patients with the lower BMI, compared with –0.39 in those with the higher BMI. Corresponding values for the 400-mg sotagliflozin group in the higher-BMI group were –0.27 and –0.45, respectively (P less than .001 for all comparisons).


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