Dapagliflozin Enhances Glycemic Control When Added to Evogliptin and Metformin in Type 2 Diabetes Patients: Study

The findings were published online in Diabetes, Obesity and Metabolism on 02 September 2024.

The study was designed by Soon Jib Yoo, The Catholic University of Korea, Seoul, Korea, and colleagues to evaluate the safety and efficacy of dapagliflozin, an SGLT2 inhibitor, versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin, a DPP-4 inhibitor, and metformin, a standard first-line medication for T2D, combination.

For this purpose, the researchers conducted a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial. Patients with glycated hemoglobin (HbA1c) levels between ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had been on stable doses of metformin (≥1000 mg) and evogliptin (5 mg) for at least eight weeks were randomized to receive either dapagliflozin 10 mg or a placebo once daily for 24 weeks.

Participants continued their metformin and evogliptin treatment throughout the trial. The primary endpoint was the change in HbA1c levels after 24 weeks of treatment compared to baseline levels.

The study revealed the following findings:

• One-hundred night eight patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99).
• At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was −0.70% (−7.7 mmol/mol).
• The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group.
• Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, fasting insulin, 2-h postprandial plasma glucose, uric acid, and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria.
• Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment.
• Adverse event rates were similar in the two groups.

Despite its clinical relevance, the researchers noted some limitations. It was conducted in a single country, limiting generalizability to other racial groups. Additionally, the findings may not apply to patients with reduced renal function or cardiovascular complications, as they were excluded. The small sample size also restricts the potential for subgroup analysis.

"Adding dapagliflozin to evogliptin and metformin significantly enhanced glycemic control, reduced body weight, insulin resistance, hyperuricemia, HSI, and microalbuminuria, and was well tolerated by patients with type 2 diabetes who were not adequately managed with the evogliptin and metformin combination alone," the researchers concluded.

Reference:

DOI: https://doi.org/10.1111/dom.15838