Long-Term Efficacy and Safety of Empagliflozin Monotherapy in Drug-Naïve Patients with Type 2 Diabetes in Indian Subgroup: Results from a 76-week Extension Trial of Phase III, Double-Blind, Randomized Study.

BACKGROUND AND OBJECTIVES: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article.

MATERIALS AND METHODS: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs).

RESULTS: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (-0.81, 95% confidence interval (CI) -1.33, -0.28; P = 0.0029) and E25 (-1.11, 95% CI - 1.60, -0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (-1.41, 95% CI - 2.51, -0.31; P = 0.0125) and E25 (-1.50, 95% CI - 2.54, -0.46; P = 0.0051) but nonsignificant with S100 (-0.75 95% CI - 1.86, -0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs.

CONCLUSION: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.