Efficacy and Tolerability of Evogliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis with Bayesian Inference Through a Quality-management System.

Abstract

PURPOSE:

Evogliptin is one of the latest dipeptidyl peptidase-4 (DPP-4) inhibitor, and a number of clinical trials have been performed following its development, including several randomized controlled trials (RCTs) performed to evaluate its efficacy and tolerability. In our study, we performed a systematic review and meta-analysis of its efficacy and tolerability by collecting RCTs and confirmed the results with Bayesian inference. Moreover, an updated quality-management system was integrated into the study process of systematic review.

METHODS:

PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for literature published between May 1990 and November 2020. We selected 6 homogeneous RCTs in 1017 subjects for efficacy and 1070 subjects for tolerability analysis. Regarding the efficacy profile, the mean differences from baseline (95% CIs) in hemoglobin (Hb) A1c and fasting plasma glucose (FPG) were generated as end points and derived from each study. Regarding the tolerability profile, risk ratios of adverse events (AEs), serious AEs, adverse drug reactions, and hypoglycemia were generated from baseline to outcome measurements as derived from each study. A subsequent meta-analysis was performed with Bayesian inference.

FINDINGS:

For HbA1c and FPG, the results suggested a statistically significant improvement with evogliptin versus placebo (HbA1c, -0.44 [95% CI, -0.54 to -0.34; P < 0.00001] and posterior median, -0.38 [95% CI, -0.51 to -0.24]; FPG, -0.61 [95% CI, -0.90 to -0.31; P < 0.0001] and posterior median, -0.48 [95% CI, -0.90 to -0.16]), but no statistically significant difference with evogliptin versus other DPP-4 inhibitors (HbA1c, -0.01 [95% CI, -0.14 to 0.12] and posterior median, -0.06 [95% CI, -0.25 to 0.12]; FPG, 0.17 [95% CI, -0.10 to 0.44] and posterior median, 0.27 [95% CI, -0.12 to 0.65]). In terms of tolerability, the overall prevalence of adverse events, including hypoglycemia, was similar between evogliptin and other DPP-4 inhibitors and placebo.

IMPLICATIONS:

Evogliptin appears more efficacious in terms of changes in HbA1c and FPG compared with placebo, with an efficacy comparable to those of other DPP-4 inhibitors, although with the limited data studied and the minuscule sample sizes, the predictions of posterior medians, mean differences, and risk ratios of HbA1c, FPG, and AEs by Bayesian inference were consistent with our findings through our quality-management system.

• Authors: Hojin Oh, Hai Duc Nguyen, In Mo Yoon, Min-Sun Kim
• Journal: Clinical therapeutics (Clin Ther) Vol. 43 Issue 8 Pg. 1336-1355 (08 2021) ISSN: 1879-114X [Electronic] United States
• PMID: 34304912 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• 4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
• Dipeptidyl-Peptidase IV Inhibitors
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Piperazines

Topics

• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (adverse effects)
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemic Agents (adverse effects)
• Piperazines