Comparative Cardiovascular Risks of Dipeptidyl Peptidase-4 Inhibitors: Analyses of Real-world Data in Korea

Abstract

Background and ObjectivesTo compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes.MethodsWe identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders.ResultsCompared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p<0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p<0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p<0.001) for gemigliptin.ConclusionsCompared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.

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

“…In our study, there was an increased risk associated with DPP‐4Is compared with α ‐GIs and BGs, but a decreased risk compared with SUs. The inconsistent results may be due, in part, to the different compositions of the endpoint (ie, whether HF or mortality was included or not) or different risks of individual drugs …”

“…However, it is difficult to compare our results with these studies because of different study purposes (class effect vs individual effect), different conditions (monotherapy vs combination therapy), and insufficient sample size for individual drugs due to limited market period in Japan (saxagliptin was introduced in 2013). Additional studies are needed to investigate the risk of individual DPP‐4Is or combined use of DPP‐4Is with other antidiabetic drugs to consider the necessity of regulatory action because of different effects on CVDs among individual DPP‐4Is …”

“…The inconsistent results may be due, in part, to the different compositions of the endpoint (ie, whether HF or mortality was included or not) or different risks of individual drugs. 25,27 With regard to cardiovascular risk associated with DPP-4Is relative to α-GIs in Asian patients, Ou et al 15 reported that there were no major differences in the risk of MI, HF, and stroke between DPP-4Is and α-GIs. In general, our results support these findings and contribute to providing more robust evidence on the widespread use of α-GIs in Asia due to its pharmacological action and lower cardiovascular risk.…”

Cardiovascular Research Using the Korean National Health Information Database

“…Dyslipidemia was defined using the ICD-10 code E78 combined with prescribing lipid-lowering agents at least once a year. 79) In addition to this operational definition, total cholesterol ≥240 mg/dL was another criteria for dyslipidemia. 60) 65) 76) …”

Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcome

“…In this issue, Ha et al 8) reported a very interesting result regarding CVD risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with type 2 diabetes using claims database of the Korean National Health Insurance System. They showed that saxagliptin, linagliptin, and gemigliptin therapies were associated with a lower risk of cardiovascular events compared to sitagliptin therapy.…”