Add-on sotagliflozin improves glycemic control in type 1 diabetes patients
medwireNews: Results of the inTandem3 study suggest that adding the sodium–glucose cotransporter (SGLT) 1 and 2 inhibitor sotagliflozin to insulin treatment improves glycemic control among patients with type 1 diabetes, but at the cost of an increased risk for ketoacidosis.
In the phase III trial, which was presented at the EASD annual meeting in Lisbon, Portugal, and published simultaneously in The New England Journal of Medicine, 1402 insulin-treated patients with type 1 diabetes were randomly assigned to receive either sotagliflozin 400 mg/day or placebo.
At week 24, 28.6% of 699 patients in the sotagliflozin group achieved a glycated hemoglobin level below 7.0% without severe hypoglycemia or diabetic ketoacidosis, compared with 15.2% of 703 patients in the placebo group.
These results gave a significant estimated between-group difference of 13.4 percentage points, Melanie Davies (University of Leicester, UK) told delegates at the EASD meeting.
Patients receiving sotagliflozin also had a significantly greater reduction in body weight, systolic blood pressure, and mean daily bolus dose of insulin from baseline to week 24 than those in the placebo group, with least-squares mean decreases of 2.98 kg, 3.5 mmHg, and 2.8 units, respectively.
Despite these benefits, the incidence of ketoacidosis was significantly higher among patients in the sotagliflozin group (3.0 vs 0.6%), particularly for those using an insulin pump (4.4% of 275 sotagliflozin-treated patients vs 0.7% of 280 in the placebo group).
We'd love to see trials looking to explore the cardiovascular benefits of these drugs in type 1 [diabetes]
Writing in a linked editorial, David Nathan (Massachusetts General Hospital and Harvard Medical School, Boston, USA) comments that this increased risk for ketoacidosis “counterbalances the increased likelihood of achieving a glycated hemoglobin level of less than 7%.”
Overall, 55.1% of patients in the sotagliflozin group and 52.5% of placebo-treated patients experienced treatment-emergent adverse events, and the corresponding rates of serious adverse events were 6.9% and 3.3%.
Patients receiving sotagliflozin were more likely to have one or more serious hypoglycemic episodes than those in the placebo group (3.0 vs 2.4%), but the rate of documented hypoglycemia, with blood glucose levels of 55 mg/dL or below, was significantly lower among participants in the sotagliflozin group (11.8 vs 15.4 per patient–year).
Commenting on these findings at the EASD meeting, John Buse (University of North Carolina School of Medicine, Chapel Hill, USA) told the audience that “SGLT inhibition really does provide meaningful benefits but at some risk to patients with type 1 diabetes,” and recommended that healthcare providers work to minimize the risk for ketoacidosis, for example, by monitoring ketone levels and starting with a low dose of SGLT2 inhibitors.
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