Dapagliflozin Linagliptin FDC Superior to Dapagliflozin Vildagliptin FDC in T2DM: Latest Indian Study

Dapagliflozin and linagliptin fixed-dose combination (FDC) is superior to dapagliflozin and vildagliptin combination therapy in controlling Hba1c, postprandial, and fasting blood glucose in uncontrolled T2DM patients, a recent Indian study has reported.

The study, designed as a multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study, included 236 participants for 18 weeks. The study aimed to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. This study is the first phase III trial to compare the effects of linagliptin and the SGLT2i dapagliflozin on patients with other molecules of the same class in a double-blind, parallel-group setting.

The participants were randomly assigned to receive either an FDC of dapagliflozin 10 mg plus linagliptin 5 mg tablets (Group A) or an FDC of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets (Group B) added to metformin monotherapy. The findings were published in the latest issue of Cureus, a part of Springer Nature.

The primary outcome was the mean change in glycated hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%.

Key Results from the Study

Effect on HbA1c: The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Refer to figure (A)

Effect on PPBG & FPG: Compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). Refer to figure (B)

There was a statistically significant reduction in FBG in the treatment A group compared to the treatment B group from baseline to week 16 (p < 0.0458). Refer to figure (C )

Figure: Mean reduction in HbA1c, PPBG & FPG from baseline at the end of week 16. Dapagliflozin 10 mg plus linagliptin 5 mg tablets (Group A) or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets (Group B)

The study concluded that compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin FDC provided clinically significant improvements in glycemic control. In view of its effectiveness, safety, and tolerability, the FDC of dapagliflozin and linagliptin is a better option for treating T2DM patients who had previously been treated with metformin monotherapy.

Reference: Dharmalingam M, Kumar Sharma S, Prakash V, et al. (April 12, 2024) Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin. Cureus 16(4): e58115. doi:10.7759/cureus.58115