Cardiovascular risks associated with dipeptidyl peptidase‐4 inhibitors monotherapy compared with other antidiabetes drugs in the Japanese population: A nationwide cohort study

Abstract

Purpose We evaluated the cardiovascular risk associated with dipeptidyl peptidase‐4 inhibitors (DPP‐4Is) as monotherapy compared with other antidiabetic drugs in Japan. Methods We conducted a nationwide cohort study involving 2 716 000 diabetes patients in Japan. New users of any antidiabetic drug as monotherapy between 1 April 2010 and 31 October 2014 were identified. Occurrences of myocardial infarction (MI), heart failure (HF), and stroke requiring hospitalization associated with DPP‐4Is were compared with those associated with biguanides (BGs), sulfonylureas (SUs), or α‐glucosidase inhibitors (α‐GIs). Adjusted hazard ratios (aHRs) for these outcomes were estimated by Cox proportional hazards model. Propensity score standardization was used to control for confounding. Results We identified 1 105 103 patients using DPP‐4Is, 278 280 patients using BGs, 273 449 patients using SUs, and 217 026 patients using α‐GIs. The risks of MI and HF for DPP‐4I users were significantly higher than those for BG users (MI: aHR, 1.48 [95%CI, 1.20‐1.82], HF: aHR, 1.46 [95%CI, 1.31‐1.62]), while significantly lower than those for SU users (MI: aHR, 0.84 [95%CI, 0.72‐0.98], HF: aHR, 0.86 [95%CI, 0.81‐0.92]). The risk of MI for DPP‐4I users was similar to that for α‐GI users, while the risk of HF for DPP‐4I users was slightly higher than for α‐GI users (MI: aHR, 0.98 [95%CI, 0.82‐1.17], HF: aHR, 1.12[95%CI, 1.04‐1.21]). Conclusions Risk of MI and HF requiring hospitalization associated with DPP‐4Is as monotherapy was significantly higher than BGs, significantly lower than SUs, and similar to α‐GIs.

Comparison of the effects on cardiovascular events between use of metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycaemic agents in Japanese patients with type 2 diabetes mellitus: a claims database analysis

“…Our results on the risk of cardiovascular events are consistent with those of previous Japanese studies that also used claims databases,13 14 where the effect on reduction in the event tended to be lower with biguanide than with DPP-4i as the first-line therapy. However, there are some differences in the study methods.…”

“…However, there are some differences in the study methods. In a 2019 study, a significant difference was observed in the reduction in the incidence of MI and HF with metformin as the first-line monotherapy 14 ; however, in the current study, a significant difference was not observed in the MDV database, and a significant difference was observed only for MI in the JMDC database during the entire study period. For the period of monotherapy, which is the same as that of the previous study, no significant difference was observed in both databases.…”

“…Regarding the study period, the previous Japanese studies13 14 evaluated the effects for the period of continued initial therapy as monotherapy. Meanwhile, since we focused on the choice of the initial treatment for type 2 diabetes in this study, the study period of the main analysis included the entire period after initial treatment as monotherapy.…”

“…13 A 2019 study comparing biguanide and DPP-4i for initial treatment reported that the risk of myocardial infarction (MI) and heart failure (HF) requiring hospitalisation was significantly higher with DPP-4i than with biguanides. 14 The study used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which is operated by the Ministry of Health, Labour and Welfare since 2009 and comprises claims data from almost all Japanese individuals and some annual medical check-up data. Therefore, the study could be considered to include a sufficient sample size with almost no bias.…”

Evolving Acceptance and Use of RWE for Regulatory Decision Making on the Benefit/Risk Assessment of a Drug in Japan

“…The NDB is a nationwide database in Japan operated by the MHLW, and contains the electronic claims data covering almost all Japanese individuals (−120 million) and special health check-up data since April 2009. 21 MID-NET® is a new medical information database network that is known to be a reliable and valuable database in Japan and stores EMRs, administrative claim data, and DPC data of over 5.3 million patients (as of December 2020) in cooperation with 10 healthcare organizations, including 23 university hospitals or core regional hospitals. 22 The purpose of these studies was to investigate the actual drug use or safety risks associated with a drug in clinical practice.…”