Sotagliflozin: First Global Approval

Sotagliflozin (Zynquista™) is a dual inhibitor of sodium-glucose co-transporters (SGLT) 1 and 2 being developed by Lexicon Pharmaceuticals and Sanofi as a treatment for type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The drug has a dual action, blunting and delaying absorption of glucose from the gastrointestinal tract and the reabsorption of glucose in the proximal tubule of the kidney, respectively. In the phase III inTandem clinical trial program in patients with T1DM, sotagliflozin as an adjunct to optimised insulin therapy produced a clinically meaningful reduction in HbA_1c levels, but was associated with a higher incidence of diabetic ketoacidosis than placebo. Sotagliflozin was recently approved for use as an adjunct to insulin in T1DM in the EU. However, the FDA Endocrinologic and Metabolic Drugs Advisory Committee was divided, citing concerns regarding diabetic ketoacidosis, leading the FDA to issue an Complete Response Letter for this indication in the USA. This article summarizes the milestones in the development of sotagliflozin leading to this first approval in the EU as an adjunct to insulin in patients with T1DM with a body mass index ≥ 27 kg/m² who have failed to achieve adequate glycaemic control despite optimal insulin therapy.