Efficacy and safety of evogliptin versus sitagliptin as add on to metformin alone in a combined russian-korean population. Evo-combi trial
Background: Dipeptidyl-peptidase-4 inhibitors (iDPP-4) are pathogenically targeted drugs for diabetes mellitus type 2 (T2DM). Evogliptin is a new member of iDPP-4 class. The drug has the longest half-elimination period among the class, and its efficacy and safety as monotherapy have been already studied in placebo-controlled randomized clinical trials. Aims: To study efficacy and safety of evogliptin as compared to sitagliptin in T2DM patients with unsatisfying glycemic control with metformin monotherapy via a multinational double blind randomized controlled trial. To compare the study results in Russian and Korean subpopulations. Materials and methods: We used a combined Russian-Korean database (1:4) of EVO-COMBI trial. 281 adult T2DM patients administered metformin alone (at least 1000 mg/day) were randomized 1:1 to add on evogliptin (142 patients) or sitagliptin (139 patients) for 24 weeks once daily. The primary endpoint was change in glycated hemoglobin (HbA1c) level at Week 24 as compared to baseline. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was < 0.35 %. Subgroup analysis for between-subpopulation difference in treatment effect was also conducted. Results: The mean between-group difference was 0.03 % [95 % CI: -0.14; 0.19 %], that confirms non-inferiority of evogliptin (mean HbA1c decrease -0.58 ± 0.70 %, p<0.001) to sitagliptin (mean HbA1c decrease -0.61 ± 0.66 %, p<0.001). Evogliptin and sitagliptin both tend to be more effective in South Korean subpopulation in terms of fasting plasma glucose lowering (p=0.030), however HbA1c decrease in subpopulations was comparable (p=0.657). Both drugs were well tolerated in both subpopulations. Adverse effects were associated mostly with gastrointestinal disorders, and the frequency was comparable between treatment groups (p>0.05). Gastrointestinal adverse effects were registered more often in Korean patients (p=0.014). There were no severe hypoglycemia. Frequency of mild hypoglycemia was comparable between evogliptin and sitagliptin (0.7 % and 5.2 %, respectively, p=0.365). Conclusions: Evogliptin 5 mg/day is non-inferior to sitagliptin 100 mg/day in T2DM patients with unsatisfying glycemic control with metformin monotherapy. Safety profile is also comparable. Efficacy-safety profile of evogliptin is comparable in Russian and South Korean subpopulations.