57th EASD: Sotagliflozin for Type 2 Diabetes

While it does not yet have FDA approval, researchers find novel dual SGLT-1/2 inhibitor, sotagliflozin, is efficacious and safe for patients with type 2 diabetes.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitor is a therapeutic drug class that provides multiple benefits (improved glycemic control, reduced body weight, and lowered incidence of heart failure and renal diseases) in managing type 2 diabetes. Therefore, the ADA 2021 guideline recommends SGLT-2 inhibitors as a second-line agent for patients with an established or high risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). In addition, sotagliflozin is a first-in-class dual SGLT-1/2 inhibitor that has been approved in Europe as adjunctive therapy for patients with type 1 diabetes.

Several trials have now been conducted to assess the effects of sotagliflozin in patients with type 2 diabetes. At the 57th annual meeting of the European Association for the Study of Diabetes (EASD), Dr. Kakotrichi presented a systematic review and meta-analysis of these trials, conducted by herself and her colleagues, to summarize the efficacy and safety of sotagliflozin in patients with type 2 diabetes.

In this meta-analysis, the authors included randomized controlled trials that compared sotagliflozin with placebo or active anti-diabetic agents in adults with type 2 diabetes for at least eight weeks. In addition, they included all trials up to January 2021 and identified ten double-blind, parallel-group, randomized trials comprising over 16,000 patients. Among ten trials, seven compared sotagliflozin with placebo, and three compared sotagliflozin with active comparators (empagliflozin, glimepiride). The efficacy outcomes included the change from baseline of HbA1c, body weight, and blood pressure. The safety outcomes included cardiovascular endpoints, serious adverse events, and discontinuation due to any adverse events.

The mean baseline characteristics were: 63.9 years old, 8.2% HbA1c, 135.6 mmHg systolic blood pressure, and 50 weeks duration of the trials. In the results of the seven trials that compared to placebo, sotagliflozin statistically improved the HbA1c levels (-0.40%, 95% CI -0.54 to -0.26), body weight (-1.32 kg, 95% CI -1.59 to -1.05), and systolic blood pressure (-2.44 mmHg, 95% CI -2.81 to -2.07). Regarding safety outcomes, sotagliflozin statistically reduced the risk of hospitalization for heart failure (OR 0.67, 95% CI 0.57 to 0.78) and myocardial infarction (OR 0.73, 95% CI 0.54 to 0.98). The effects of sotagliflozin on all-cause mortality, cardiovascular mortality, and stroke were indifferent. Sotagliflozin was associated with increased risk for some other side effects, including diarrhea (OR 1.47, 95% CI 1.26 to 1.71), volume depletion (OR 1.27, 95% CI 1.08 to 1.50), and genital infections (OR 2.98, 95% CI 2.16 to 4.13). In comparison with active comparatives, sotagliflozin showed no differences in the efficacy outcomes.

In conclusion, the authors stated that sotagliflozin is beneficial in glycemic control, weight loss, and blood pressure management. In addition, even though several side effects were reported with sotagliflozin, severe hypoglycemia and diabetic ketoacidosis were not associated with sotagliflozin. Of note, one of the reasons the FDA denied the approval of sotagliflozin as an adjunct agent for type 1 diabetes was due to profound incidences of diabetic ketoacidosis. Therefore, based on the result of this meta-analysis of multiple trials, diabetic ketoacidosis is more of a common complication of type 1 diabetes than the side effect of this drug. Furthermore, another meta-analysis conducted by Avgerinos et al. also showed similar efficacy and safety profile of sotagliflozin in managing type 2 diabetes. However, due to the inclusive effects on the cardiorenal outcomes, more extensive studies with the primary outcome focus on these outcomes are needed to evaluate the long-term effects of sotagliflozin further.

Practice Pearls:

• Sotagliflozin can safely reduce HbA1c level, body weight, and blood pressure for patients with type 2 diabetes.
• Sotagliflozin also offers benefits in reducing the risk of heart failure and myocardial infarction.
• Sotagliflozin is not currently FDA approved in the U.S., and long-term effects on cardiorenal outcomes should be further validated.

Kakotrichi, Panagiota. “EASD 2021: Meta-Analysis Demonstrates Sotagliflozin Offers Glycemic and Cardiovascular Benefits in Type 2 Diabetes”

Avgerinos, Ioannis et al. “Sotagliflozin for patients with type 2 diabetes: A systematic review and meta-analysis.” Diabetes, obesity & metabolism,

American Diabetes Association. “9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021.” Diabetes care

Ding Nguyen, PharmD Candidate, University of South Florida Taneja College of Pharmacy