Association of sulphonylureas and dipeptidyl peptidase-4 inhibitors with cardiovascular disease : population-based cohort study

Abstract

The prevalence of type 2 diabetes (T2DM) is rising across the world with an estimation to reach 690 million by 2045. Although the imminent treatment target is to keep the blood glucose under control, the ultimate goal is to reduce its complications. Sulphonylureas (SUs) are very effective in lowering hyperglycemia and are also inexpensive. Therefore, they serve as cost effective treatment options. However, their use has been decreasing because there were concerns that SUs could increase the risk of cardiovascular (CV) events. Nonetheless, studies regarding their effects on the cardiovascular system have been conflicting. As SUs are commonly used in Hong Kong (HK), it is worth performing population-based study to assess their effects on the cardiovascular system. Therefore, the aim of the study was to assess the association between the use of SUs and CV events in clinical practice in HK.A retrospective cohort study using dipeptidyl-peptidase 4 (DPP4) inhibitors as active comparator was conducted. Data was extracted from Clinical Data and Analysis Reporting System of Hospital Authority. Patients with newly prescribed metformin plus DPP4 inhibitor (Met-DPP4) or metformin plus sulphonylureas (Met-SU) during 2010-2016 were included and matched in 1:4 ratio using propensity score. The study was divided into two chapters. The first chapter excluded patients with cardiovascular disease (CVD) diagnosed before index date while the second chapter included these patients. The main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction (MI), stroke, hospitalization due to heart failure (HF) and revascularization. Secondary outcomes were individual component of the primary outcome and all-cause mortality. Hazard ratios (HRs) was estimated using cox proportional hazard regression.For the cohort with pre-existing CVD excluded, 9,141 patients were in the Met-SU group and 2,962 patients were in the Met-DPP4 group. The incidence of MACE for Met-SU was 19.5 per 1,000 person-years and that for Met-DPP4 was 14.1 per 1,000 person-years [HR=1.29, 95% CI: 0.87-1.92; p=0.28]. No significant associations were observed with other CV outcomes except for stroke, where the incidence for Met-SU was 9.5 per 1,000 person-years and that for Met-DPP4 was 3.9 per 1,000 person-years [HR=2.49, 95% CI: 1.22-5.11; p=0.013]. For the cohort including prior CVD cases, there were 11,363 patients in the Met-SU group and 2,999 patients in the Met-DPP4 group. The incidence of MACE for Met-SU was 28.8 per 1,000 person-years and that for Met-DPP4 was 29.9 per 1,000 person-years [HR=0.85, 95% CI: 0.66-1.10; p=0.217]. No significant associations were observed with other CV outcomes including stroke.SUs were not associated with an increased risk of MACE, even in the presence of established CVD. It was concluded that the use of SUs was safe in terms of their CV effects. Therefore, they still serve as useful treatment options for T2DM, especially when treatment cost is a concern.