No oral medication has ever been approved for the treatment of type-1 diabetes, but a phase 3 trial shows that sotagliflozin has the potential to become the first. Sotagliflozin (LX4211, Lexicon Pharmaceuticals) is an investigational drug for patients with type-1 diabetes that has shown promise in improving glucose control without any increase in severe hypoglycemia or diabetic ketoacidosis compared to insulin alone.
Results of the global phase 3 trial published in the New England Journal of Medicine found that among 1,402 patients with type-1 diabetes treated with sotagliflozin, the drug showed clinically meaningful and statistically significant effects on glucose control. Concentrations of hemoglobin A1C were improved. Patients experienced a lower rate of confirmed severe hypoglycemia than that observed in patients on placebo and also had weight loss.
Lead investigator Satish Garg, MD, professor of medicine and pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado Anschutz Medical Campus, said sotagliflozin has the potential to become the first new treatment innovation for type-1 diabetes in nearly a century since insulin.
Most patients do not achieve optimal glycemic control with insulin alone. A1C concentrations, hypertension, and reduction in body weight are critical issues which significantly impact people living with type 1 diabetes.
"If approved by the FDA, sotagliflozin may be the first oral drug that helps patients with type 1 diabetes in improving their glucose control without any weight gain or increase and severe hypoglycemia," Garg said. "If long-term use continues to show similar metabolic improvements in patients with type-1 diabetes, it is likely that the long-term complications of diabetes would be significantly reduced."
Sotagliflozin would be used in conjunction with insulin. Trial participants taking the drug as an oral pill alongside traditional insulin treatments experienced significant improvements in glucose control, a drop in systolic and diastolic blood pressure, and weight loss. Garg said sotagliflozin may reduce the adverse effects of insulin and the dose patients need.
Sotagliflozin is a dual inhibitor that works by inhibiting two sodium-glucose transporters: SGLT1 and SGLT2. Each modulates glucose levels. SGLT1 regulates the uptake of glucose in the gut while SGLT2 regulates the re-uptake of glucose in the kidney, according to the authors.
The inTandem3 study was a double-blind, placebo controlled, randomized phase 3 trial including adults with type-1 diabetes at 133 sites worldwide. In conjunction with this publication, the data were announced September 13 at the 53rd Annual Meeting of the European Association Study for Diabetes in Lisbon, Portugal.
The 24-week trial evaluated the safety and efficacy of sotagliflozin at 400 mg per day in randomized patients treated with any insulin regimen––pumps or injections. Eligible patients included men and nonpregnant women 18 years of age and older; they were required to self-monitor blood glucose.
The study met its primary endpoint with statistical significance, demonstrating the superiority of sotagliflozin 400 mg compared to placebo in the proportion of patients with A1C less than 7% at week 24, no episode of severe hypoglycemia, and no episode of diabetic ketoacidosis after randomization.
The outcome on every secondary endpoint favored sotagliflozin over placebo, achieving statistical significance for all four secondary endpoints, including change from baseline in A1C, body weight, systolic blood pressure in patients with baseline SBP less than or equal to 130 mm Hg, and bolus insulin dose. Sotagliflozin significantly reduced A1C compared to placebo after 24 weeks of treatment.
"As is known with sodium glucose cotransporter 2 (SGLT2) inhibitors, patients experienced more episodes of diabetic ketoacidosis in the trial," Garg said. Diarrhea and genital mycotic infection also affected participants more than placebo, but less than 1% discontinued the study due to these effects.
Source: University of Colorado Anschutz Medical Campus; September 13, 2017.