Researchers seek development of drug therapies and technologies to assist in achieving additional time in glucose target range and less hypoglycemia.
Sotagliflozin, a dual sodium glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is an investigational treatment that holds promise for improving such outcomes in people with T1D.
Sotagliflozin improves glucose control by reducing glucose absorption in the gastrointestinal (GI) tract (SGLT1 inhibition) and by inhibiting glucose reabsorption in the kidney (SGLT2 inhibition).1 The degree of SGLT1 inhibition with sotagliflozin is unique when compared to other currently available agents, and results in improvements in postprandial glucose excursions.1 Additional data suggest that SGLT1 inhibition may also stimulate the release of GI peptides, such as GLP-1 and others, that are important in glycemic control and satiety.2
A pooled analysis of continuous glucose monitoring (CGM) data obtained from sub-studies of the in Tandem1 (NCT02384941) and in Tandem2 (NCT02421510) phase 3 clinical trials was recently presented in poster format.3 The in Tandem1 and in Tandem2 studies explored the use of oral sotagliflozin 200 mg and 400 mg in adults with T1D on optimized insulin therapy.3 The insulin optimization protocol within the studies was rigorous, with prandial and basal insulin titrated to achieve fasting glucose values of 80-130 mg/dL and 1- to 2-hour postprandial glucose values <180 mg/dL. Participants within the CGM sub-studies underwent blinded CGM during prespecified periods during the 24-week treatment period of each study, respectively. The primary objective of the sub-study was to explore the change from baseline to week 24 in percent time spent: 1) within the target glucose range (70-180 mg/dL), 2) outside of the target range, 3) above target range (>180 mg/dL), and below the target range (<70 mg/dL).3
The pooled CGM data from the two phase 3 clinical trials showed several benefits with use of sotagliflozin when compared to placebo as add-on to optimized insulin therapy:3
- Dose-related increase in glucose time in range (70-180 mg/dL), with a corresponding decrease in time spent >180 mg/dL and without an increase in time spent <70 mg/dL.
- A numeric decrease in hypoglycemia as measured by CGM (events per patient per day) and percentage of time spent per day with a glucose <55 mg/dL.
- A decrease in postprandial glucose values of approximately 35 mg/dL and 50 mg/dL with sotagliflozin 200 mg and 400 mg, respectively.
This pooled CGM study provides important insight on the potential role of sotagliflozin in patients with T1D. Data from this analysis supports the notion that sotagliflozin can lead to improvements in time within glucose range without additional hypoglycemia. It is important to consider that these improvements were observed on top of diligent insulin titration to achieve and maintain standard of care fasting and postprandial glucose values. Sotagliflozin is currently under review by the U.S. Food and Drug Administration (FDA) as an oral treatment in addition to insulin therapy to improve blood glucose control in adults with T1D. The target FDA action date for the submission is anticipated as March 22, 2019.4
- Sotagliflozin improves glucose control by reducing glucose absorption in the gastrointestinal (GI) tract (SGLT1 inhibition) and by inhibiting glucose reabsorption in the kidney (SGLT2 inhibition).1
- Adding oral sotagliflozin to insulin treatment can increase the time in target glucose range.
- Sotagliflozin Improves time in target range without increase in hyperglycemia.
- Link to Poster Presentation: https://ada.scientificposters.com/epsAbstractADA.cfm?id=3
Sands AT, Zambrowicsz BP, Rosenstock J, et al. Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes. Diabetes Care 2015;38(7):1181-1188
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-2157
Danne T, Cariou B, Buse JB, et al. Increased time in glucose target range with sotagliflozin as adjunct therapy to insulin in adults with type 1 diabetes as demonstrated by 24-week continuous glucose monitoring (inTandem 1, NCT02384941; inTandem2, NCT02421510). Presented at: Metabolic & Endocrine Disease Summit (MEDS); San Diego, CA; August 1-4, 2018.
Seema Badrbigi, PharmD Candidate , Joshua J. Neumiller, PharmD, CDE, FAADE, FASCP