Sotagliflozin: a dual sodium-glucose co-transporter-1 and-2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus

AimsTo evaluate the evidence for the novel dual sodium-glucose co-transporter-1 (SGLT1) and -2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy of SGLT2 inhibitors by additionally reducing intestinal glucose absorption. MethodsThe search terms sotagliflozin', LX4211', SGLT' and diabetes' were entered into PubMed. Evidence for the pharmacokinetics, pharmacodynamics, safety and efficacy of sotagliflozin in Type 1 and 2 diabetes was extracted from the retrieved literature, critically evaluated, and contextualized in relation to data on existing SGLT2 inhibitors. ResultsThere is convincing evidence from a range of phase II and III clinical trials that sotagliflozin significantly improves glycaemic control in both Type 1 and Type 2 diabetes. Additional benefits, such as smaller postprandial plasma glucose excursions, lower insulin requirements, appetite suppression and weight loss have been documented. While this is encouraging, several safety concerns remain; a dose-dependent increase in the rate of diabetic ketoacidosis, diarrhoea and genital mycotic infection is apparent, although statistical exploration of the data regarding such events is currently lacking. Speculatively, use of a 200-mg rather than a 400-mg dose may help to limit unwanted effects. ConclusionsThe current evidence for sotagliflozin in diabetes appears promising. Further studies sufficiently powered to assess present and emerging safety concerns, as well as to identify individuals for whom sotagliflozin may be of particular benefit/harm would now be informative for regulatory decision-making. Direct comparisons with existing SGLT2 inhibitors are also needed to determine relative safety/efficacy profiles for the different indications.