Sotagliflozin: a combined SGLT1/SGLT2 inhibitor to treat diabetes

ABSTRACT

Introduction: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. The agent blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1. Initial studies were directed at type 1 diabetes.

Areas covered: The published information on sotagliflozin is reviewed, along with the results of several pivotal Type 1 diabetes trials.

Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability in Type 1 diabetes patients. Several other SGLT2 inhibitors have been associated with a tendency to diabetic ketoacidosis (DKA). In the type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety concern arises from the as yet unknown potential risks in women of child bearing potential. The sotagliflozin development program has now been extended to trials in type 2 diabetes. In type 2 diabetes, long-term studies will be needed to assess the benefits and risks of the agent as a possible alternative to currently marketed SGLT2 inhibitors.

KEYWORDS:

• Gene knockout models
• SGLT1
• SGLT2
• diabetic ketoacidosis
• empagliflozin
• dapligliflozin

Information resources

Von Mering J. Ueber kunstlichen diabetes. Centralbl. Med. Wiss. 1886, xxii, 531.**Historical publication on the first SGLT1/SGLT2 inhibitor

Rieg T, Masuda T, Gerasimova M, et al. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. Am J Physiol Renal Physiol 2014; 306: F188–F193

Lapuerta P, Zambrowicz B, Strumph P, et al. Development of sotagliflozin, a dual sodiumdependent glucose transporter 1/2 inhibitor. Diab Vasc Disease Res 2015; 12:101-110

Rendell MS, Jovanovic L. Targeting postprandial hyperglycemia. Metabolism. 2006; 55: 1263–1281.

Garg SK, Henry RR, Banks P, et al. Effects of Sotagliflozin added to insulin in patients with Type 1 Diabetes. N Engl J Med. 2017;377:2337–2348

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors - FDA https://www.fda.gov/Drugs/DrugSafety/ucm446852.htm

Lexicon Pharmaceuticals, Inc. www.lexpharma.com/

Declaration of interest

MS Rendell is Executive Director of the Association of Diabetes Investigators and Medical Director of the Rose Salter Medical Research Foundation and has received grants to conduct several sotagliflozin clinical research studies. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author was supported by The Association of Diabetes Investigators and the Rose Salter Medical Research Foundation.