Diabetes Metab J.  2023 Nov;47(6):808-817. 10.4093/dmj.2022.0387.

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

• Moon JS
• Park IR
• Kim HJ
• Chung CH
• Won KC
• Han KA
• Park CY
• Won JC
• Kim DJ
• Koh GP
• Kim ES
• Yu JM
• Hong EG
• Lee CB
• Yoon KH

• KMID: 2548157
• DOI: http://doi.org/10.4093/dmj.2022.0387

Abstract

Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Keyword

Dapagliflozin; Diabetes mellitus, type 2; Dipeptidyl-peptidase IV inhibitors; Drug therapy, combination; Metformin

Figure

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  Fig. 1. Patient disposition.

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  Fig. 2. Primary endpoint as change in the glycosylated hemoglobin (HbA1c) level. Time course of adjusted mean change in the HbA1c level from the baseline (A) and adjusted mean change in the HbA1c level from baseline to weeks 24 and 52 (B). Data expressed as mean and 95% confidence interval (CI). SE, standard error. aP<0.0001 between evogliptin and placebo.

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  Fig. 3. Secondary endpoint. Proportion of glycemic achievement at week 52 (A), time course of adjusted mean change in the fasting plasma glucose (FPG) level from baseline (B), adjusted mean change in the FPG level from baseline to week 52 (C), adjusted mean change in the mean daily glucose (MDG) level (D) and homeostatic model assessment of β-cell function (HOMA-β) from baseline to week 52 (E). (B) Data expressed as mean and 95% confidence interval (CI). OR, odds ratio; SE, standard error. aP<0.0001, bP<0.01 between placebo and evogliptin.

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