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

• Published in: Diabetic medicine Vol. 35; no. 8; pp. 1037 - 1048
• Main Authors: Sims, H., Smith, K. H., Bramlage, P., Minguet, J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-08-2018
• Subjects: Appetite; Blood Glucose - drug effects; Blood Glucose - metabolism; Clinical trials; Decision making; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diarrhea; Glucose; Glucose transporter; Glycosides - therapeutic use; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Intestine; Ketoacidosis; Pharmacodynamics; Pharmacokinetics; Safety; Sodium; Sodium-Glucose Transporter 1 - antagonists & inhibitors; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.13645

Aims
To 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.
Methods
The 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.
Results
There 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.
Conclusions
The 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.
What's new?
Several sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are available for the treatment of Type 2 diabetes mellitus; however, sotagliflozin is the first dual sodium‐glucose co‐transporter‐1/SGLT2 inhibitor to reach phase III trials for the Type 1 diabetes indication.
Sotagliflozin has demonstrated good efficacy in improving glycaemic control in Types 1 and 2 diabetes, with additional weight loss benefits; however, several drug‐related adverse events remain a concern, including diabetic ketoacidosis, diarrhoea and genital mycotic infection.
The data presented in this review suggest that regulatory approval for sotagliflozin in Type 1 diabetes may be on the horizon, potentially providing physicians with a novel option for combatting the metabolic disorder.