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Sotagliflozin Reduces A1C With Less Insulin in Type 1 Diabetes, but DKA Rates Increase

Article

Researchers noted that the oral therapy functions independently of insulin to carry excess blood glucose out of the system.

Results presented this week at the European Association for the Study of Diabetes in Lisbon, Portugal, show that sotagliflozin, an oral therapy known as a dual inhibitor, lowered glycated hemoglobin (A1C) and helped patients with type 1 diabetes (T1D) lose weight and control blood pressure, in part because they needed less insulin.

However, the study, called inTandem3, also showed higher rates of diabetic ketoacidosis (DKA) among patients taking the study drug than those taking placebo, a result consistent with findings in related studies of T1D patients taking a popular drug now approved for patients with type 2 diabetes (T2D).

The study, also published in The New England Journal of Medicine, found that 28.6% of the patients in the sotagliflozin group achieved an A1C of 7.0% or less by week 24 without severe hypoglycemia or DKA, compared with 15.2% of those taking placebo. Patients taking sotagliflozin also lost significantly more weight, a mean difference of 2.98 kg. The sotagliflozin patients needed less insulin—a reduction of 2.8 units per day for basal doses. Reductions in fasting plasma glucose levels and systolic and diastolic blood pressure were all improved for the sotagliflozin group compared with the placebo group. Meanwhile, the sotagliflozin group had a DKA rate of 3.0%, compared with 0.6% in the placebo group.

For several years, sodium glucose co-transporter-2 (SGLT2) inhibitors have reshaped the T2D market with a unique mechanism of action that blocks a protein that reabsorbs glucose, causing the excess blood sugar to be expelled through the urine. Drugs in the class not only lower A1C but also reduce hypertension; 2 drugs in the class—empagliflozin and canagliflozin—have been shown to have cardiovascular benefits.

SGLT2 inhibitors have been studied in T1D patients with the hope that they would help reduce glycemic variability—the “roller coaster” effect of rising and falling blood sugar—and offer similar benefits in blood pressure and weight control. Sotagliflozin promises to go a step further by also blocking the SGLT1 protein, further reducing the blood sugar spikes after a meal.

Studies of canagliflozin in T1D patients have shown higher rates of DKA, a point noted in an editorial accompanying the study.

Researchers note that the mechanism of action for sotagliflozin works separately from insulin, and they expressed excitement that this could be the most important therapeutic development for T1D patients since the approval of insulin nearly 100 years ago.

"Sotagliflozin added to insulin therapy can potentially help patients with type 1 diabetes improve their glucose control and hopefully manage the disease with fewer complications," said lead study author Satish K. Garg, MD, of the University of Colorado, in a statement. "This would not be a replacement for insulin; it is an adjunctive therapy. However, because it works in the gut and the kidneys, it doesn't require insulin to have an effect."

Lexicon and Sanofi are developing sotagliflozin.

Reference

Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes [published online September 13, 2017]. N Engl J Med. 2017; DOI: 10.1056/NEJMoa1708337

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