Data from the SOTA-INS CGM Phase 3 clinical trial indicates that sotagliflozin, when administered once daily at a 400 mg dose, improves time-in-range (TIR) and several continuous glucose monitoring (CGM) parameters, including glucose variability, in insulin-treated type 2 diabetes (T2D) patients. The findings, which also showed positive trends with a 200 mg dose, were presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD). These results suggest a potential therapeutic benefit for patients struggling to manage their glucose levels despite insulin therapy.
The SOTA-INS CGM study aimed to evaluate the impact of sotagliflozin on TIR, as measured by CGM, in individuals with T2D. The primary endpoint focused on the mean change in the percentage of time spent within the target glucose range (70-180 mg/dL [3.9-10.0 mmol/L]) over a 24-hour period for the 400 mg sotagliflozin dose compared to placebo.
The American Diabetes Association (ADA) recommends a TIR target of at least 70% (17 hours) for individuals with type 1 diabetes (T1D) or T2D. The study revealed that once-daily sotagliflozin at 200 mg and 400 mg resulted in TIR values of 15.3 and 15.9 hours, respectively, approaching the ADA target. These values were accompanied by modest reductions in time-above-range (TAR) and mild increases in time-below-range (TBR).
Sotagliflozin's Mechanism of Action
Sotagliflozin is an oral inhibitor of sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney, while SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. By inhibiting both SGLT1 and SGLT2, sotagliflozin offers a dual mechanism for glucose control.
Clinical Implications
"We are encouraged by the observation...that sotagliflozin’s dual inhibition of SGLT2 and SGLT1 may offer an additional therapeutic option to improve glycemic control for people with type 2 diabetes on basal insulin," said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. While Lexicon is not pursuing a T2D indication, this study supports the value of inhibiting SGLT1.
Sotagliflozin has previously demonstrated glycemic efficacy and improvements in TIR as an adjunct to insulin therapy in people with T1D who participated in the inTandem clinical trial program.
