Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study.

Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE

Original Publication: [London] : BMJ Publishing Group Ltd, 2011-

Diabetes Mellitus, Type 2*/epidemiology ; Metformin*/adverse effects ; Dipeptidyl-Peptidase IV Inhibitors*/adverse effects ; Myocardial Infarction*/complications ; Heart Failure*/epidemiology ; Piperazines*; Humans ; Cohort Studies ; Retrospective Studies ; Treatment Outcome ; Hypoglycemic Agents/adverse effects ; Sulfonylurea Compounds/adverse effects

Objective: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice.
Design: A retrospective cohort study.
Setting: Korean Health Insurance Review and Assessment database.
Participants: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018.
Interventions: Initiation of combination therapy with evogliptin.
Primary and Secondary Outcome Measures: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs.
Results: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51).
Conclusions: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.
Competing Interests: Competing interests: HEJ and I-SO report the receipt of research funding from the National Research Foundation of South Korea, outside the submitted work. J-YS reports the receipt of research funding from the Ministry of Food and Drug Safety, Ministry of Health and Welfare, National Research Foundation and Government-wide R&D Fund for Infectious Disease Research of South Korea, as well as grants from Amgen, Pfizer, GSK and Yungjin, outside the submitted work. Authors disclose no other relevant potential conflicts of interest.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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Keywords: CARDIOLOGY; CLINICAL PHARMACOLOGY; Diabetes & endocrinology

0 (4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one)
0 (Hypoglycemic Agents)
9100L32L2N (Metformin)
0 (Sulfonylurea Compounds)
0 (Dipeptidyl-Peptidase IV Inhibitors)
0 (Piperazines)

Date Created: 20240416 Date Completed: 20240418 Latest Revision: 20240421

20240421

PMC11029454

10.1136/bmjopen-2023-077084

38626972