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Comparative Study
, 18 (9), 916-24

Comparative Risk of Major Cardiovascular Events Associated With Second-Line Antidiabetic Treatments: A Retrospective Cohort Study Using UK Primary Care Data Linked to Hospitalization and Mortality Records

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Comparative Study

Comparative Risk of Major Cardiovascular Events Associated With Second-Line Antidiabetic Treatments: A Retrospective Cohort Study Using UK Primary Care Data Linked to Hospitalization and Mortality Records

S S Zghebi et al. Diabetes Obes Metab.

Abstract

Aims: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors.

Methods: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications.

Results: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen.

Conclusions: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

Keywords: DPP-4 inhibitor; cardiovascular disease; pharmaco-epidemiology; sulphonylureas; thiazolidinediones; type 2 diabetes.

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