Abstract
BackgroundTo determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort.MethodsFrom a nationwide cohort in Korea (2008–2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models.ResultsDuring a median follow-up of 19.6 months (interquartile range 7.2–36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81–1.23), IS (HR, 0.95; 95% CI 0.74–1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46–1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41–3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07–2.04).ConclusionsThis real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.
Highlights
To determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort
Previous cardiovascular outcome trials for DPP4i including the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE), Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin (TECOS), and Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis in Myocardial Infarction-53 (SAVOR TIMI-53) have reported no significant increase in major adverse cardiovascular events (MACEs) compared to placebo [2,3,4,5]
Study population The cohort included a total of 23,635 patients; 16,803 patients were treated with a DPP4i plus metformin, and 6832 were treated with a SU plus metformin (Additional file 2: Figure S1)
Summary
To determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort. An exceptional warning signal of higher risk of hospitalizations for heart failure (HHF) of DPP4i was observed in the SAVOR TIMI-53 trial [4]. There have been a growing number of studies focusing on the association between DPP4i and risk of heart failure (HF). In a large observational study of incretin-based drugs, DPP4i was not associated with an increased risk of HHF in patients with type 2 diabetes, with or without a history of HF [8]. The other studies even indicated that DPP4i reduced the risk of HHF compared with other comparators such as sulfonylurea [9, 10]
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