A Randomized, Double-Blind, Parallel-Group PhaseIII Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type2 Diabetes with Metformin.

Abstract

The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10mg) and linagliptin (5mg) in comparison to linagliptin 5mg (Trajenta) in patients with insufficiently controlled type2 diabetes mellitus (T2DM) on metformin monotherapy. The double-blind, randomized, multicentric, parallel-group phaseIII trial screened 287 adult patients with T2DM (age 18-65years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000mg/day for at least 28days. Patients with HbA1c of 7.5-10.5% (58-91mmol/l) (n = 232) after 2weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5mg or linagliptin 5mg for 16weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75mmol/l and > 75mmol/l)). A total of 225 subjects completed 16weeks of treatment, 115 patients in the test group and 110 patients in the reference group. Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16weeks (mean reduction, - 1.28% vs - 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase4 (DPP4)/sodium-glucose co-transporter2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10mg) in the FDC, a short study duration (30weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. CTRI/2022/08/044563; 01/08/2022.