Korean Circ J.  2018 May;48(5):395-405. 10.4070/kcj.2017.0324.

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

• Ha KH
• Kim B
• Shin HS
• Lee J
• Choi H
• Kim HC
• Kim DJ

• KMID: 2414908
• DOI: http://doi.org/10.4070/kcj.2017.0324

Abstract

BACKGROUND AND OBJECTIVES
To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes.
METHODS
We 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.
RESULTS
Compared 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.
CONCLUSIONS
Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.

Keyword

Type 2 diabetes mellitus; Cardiovascular diseases; Dipeptidyl-peptidase IV inhibitors

MeSH Terms

Atrial Fibrillation
Cardiovascular Diseases
Comorbidity
Diabetes Mellitus, Type 2
Dipeptidyl-Peptidase IV Inhibitors
Dyslipidemias
Hypertension
Infarction
Korea*
Linagliptin
National Health Programs
Platelet Aggregation Inhibitors
Proportional Hazards Models
Renal Insufficiency, Chronic
Sitagliptin Phosphate
Stroke
Dipeptidyl-Peptidase IV Inhibitors
Linagliptin
Platelet Aggregation Inhibitors
Sitagliptin Phosphate

Figure

• 

  Figure 1 Flow of people through study. CVD = cardiovascular disease; DPP-4i = dipeptidyl peptidase-4 inhibitor.

• 

  Figure 2 Cumulative incidence of cardiovascular events by different DPP-4is. (A) Main analysis. (B) Analysis of health screening data. DPP-4i = dipeptidyl peptidase-4 inhibitor; HR = hazard ratio.

• 

  Figure 3 Subgroup analysis by sex, age group, hypertension, dyslipidemia, microvascular complication. These analyses were adjusted to address potential confounding by sex, age, duration of DPP-4i use, use of other glucose-lowering drugs (metformin, sulfonylurea, thiazolidinedione, or insulin), use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, and microvascular complications of diabetes (retinopathy, neuropathy, or nephropathy), the CCI score, and calendar index year. CCI = Charlson comorbidity index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitor; HR = hazard ratio; PY = person-years.

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