Efficacy and Safety of Enavogliflozin as Add-on in Adults with Type 2 Diabetes Mellitus Inadequately Controlled with Insulin or Insulin with Other Antidiabetic Drugs

Abstract

Background: The study evaluated the efficacy and safety of enavogliflozin, a novel, promising selective sodium-glucose cotransporter 2 inhibitor, as an add-on in adults with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin alone or combined with other antidiabetic drugs (OADs).

Methods: The double-blind, placebo-controlled, multicenter trial was conducted in South Korea and Thailand. Individuals with glycosylated hemoglobin (HbA1c) ≥7.5% after ≥8-week treatment with background insulin alone or combined with ≤2 OADs were randomized to receive enavogliflozin 0.3 mg or placebo (n=116 each) for 24 weeks. The primary outcome was a change in HbA1c at week 24. Secondary outcomes included, among others, changes in body weight, blood pressure, and other measures of glycemic control. Adverse events (AEs) were investigated throughout the study (Clinical trial registration number: NCT05466643).

Results: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.9% (P<0.001). Also, placebo-adjusted mean changes in fasting plasma glucose (-32.4 mg/dL, P<0.001), body weight (-1.3 kg, P<0.001), and total daily dose of insulin (-1.3 units, P=0.010) at week 24 were statistically significant. In addition, a significant decrease in blood pressure and fasting C-peptide was observed in the enavogliflozin group, along with a significant increase in homeostasis model assessment of β-cell function, yet without a concomitant change in homeostasis model assessment of insulinresistance. No significant increase in treatment-related AEs was observed for enavogliflozin.

Conclusion: Enavogliflozin 0.3 mg/day is an efficacious and safe add-on treatment option in T2DM patients controlled inadequately with insulin alone or combined with OADs.

Keywords: Diabetes mellitus, type 2; Hypoglycemic agents; Insulin; Randomized controlled trial; Sodium-glucose transporter 2 inhibitors.