Triple-drug combo reduces HbA1c in T2D

Adding evogliptin, a novel dipeptidyl peptidase-4 inhibitor, to dapagliflozin and metformin significantly reduced HbA_1c level in patients with uncontrolled type 2 diabetes (T2D), according to a study presented at EASD 2022.

This multicentre, double-blind, placebo-controlled, phase III trial involved 283 patients (mean age 56.65 years, 59.72 percent female) with T2D (mean HbA_1c 7.91 percent; mean diabetes duration 10.29 years) inadequately controlled with dapagliflozin and metformin. Participants were randomized to receive either evogliptin 5 mg once daily (n=141) or placebo (n=142) in addition to dapagliflozin 10 mg/day and metformin ≥1,000 mg/day for 24 weeks. A long-term extension period followed thereafter wherein all patients continued treatment for an additional 28 weeks. [EASD 2022, abstract 599]

At 24 weeks, patients treated with evogliptin achieved a significantly greater reduction in HbA_1c level from baseline compared with placebo (least squares [LS] mean difference, -0.65 percent; p<0.0001), which was sustained through 52 weeks (LS mean difference, -0.55 percent; p<0.0001).

Fasting plasma glucose was also significantly reduced among those on evogliptin than those on placebo at both 24 weeks (LS mean difference, -14.61; p<0.0001) and 52 weeks (LS mean difference, -7.28; p=0.0069).

Significantly more patients on evogliptin achieved the glycaemic targets of HbA_1c <7.0 percent and <6.5 percent (odds ratio, 5.62; p<0.0001 and 6.43; p<0.01, respectively) than those on placebo.

In addition, a significant improvement in HOMA-β* was observed in the evogliptin group than the placebo group at weeks 24 and 52 (LS mean, 9.15 and 9.04, respectively; p<0.01 for both weeks) compared with placebo recipients.

Adverse event (AE) rates were similar between the evogliptin and placebo groups (35.46 percent vs 34.04 percent), with no serious AEs reported in both groups. None of the patients experienced a major hypoglycaemic event.

“Long-term triple combination with evogliptin [added] to dapagliflozin and metformin demonstrated a superior HbA_1c reduction and glycaemic control compared to placebo without any [serious] AEs in patients with T2D,” said Dr Jun Sung Moon from the Department of Internal Medicine at Yeungnam University College of Medicine in Daegu, Republic of Korea.

This triple therapy combination was well tolerated, and represents a potential new option in treating patients with poor glycaemic control, he added.