The Effect of Sulfonylureas on the Cardiovascular Risk of Patients with Type II Diabetes Mellitus: a Pharmacoepidemiological Study Based on National Health Insurance Research Database
Date Issued
2009
Date
2009
Author(s)
Wu, Yi-ting
Abstract
Background Macrovascular complication is one of the main causes of death in patients with type 2 diabetes. In 1970s, the large clinical trial, University Group Diabetes Program (UGDP) study, pointed out that the first generation sulfonylureas (SU), tolbutamide, could be associated with higher cardiovascular mortality. Although it had been found that sulfonylureas would inhibit the K(ATP) channel in cardiovascular system to prevent the ischemic preconditioning, there has not been any large clinical trial investigating the controversial issue. The results of observational studies based on databse were not consistent with each other. Since sulfonylureas remain the mainstay in the pharmacotherapy of diabetes and to our knowledge, there has not been any pharmacoepidemiological study designed for this issue in Taiwan, so we conducted the present study to provide a reference for clinical medical staffs to select medications.bjective The study aimed to assess the association between the exposure of sulfonylureas and the risk of cardiovascular events on new users of antidiabetic medications, and furthermore, to compare the effects of individual sulfonylureas on the cardiovascular events.ehtod This was a retrospective cohort study based on the National Health Insurance Research Database (NHIRD) in Taiwan. We established a cohort of patients with diabetes and aged older than 18 years, who initiated any antidiabetic medications between January 2001 and December 2007.escriptive analysis. We divided our cohort into 2 groups according to the exposure of sulfonylureas. The SU group was composed of the patients who had ever used sulfonylureas, and the Non-SU group included the ones who had never used sulfonylureas. We compared the demographic characteristics and the patterns of the usage of antidiabetic and cardiovascular medications between the 2 groups. Besides, we divided the SU group into 2 sub-groups: the GLY group was the patients who had ever used glyburide, and the Non-GLY group was the ones who had never used. And the above comparison was conducted for the 2 sub-groups.urvival analysis. There were 3 end points in the present study: hospitalization for acute myocardial infarction and coronary revascularization (MI event), hospitalization for congestive heart failure (HF event), and hospitalization for ischemic stroke (IS event). We fitted 2 multivariate time dependent Cox proportional hazard models to evaluate the adjusted hazard ratio (HR) of all sulfonylureas and individual sulfonylureas for each end point. One of the models was constructed to estimate the HR for patients who exposed sulfonylureas during 30 days before the event, and the other one was similar but to assess the exposure of sulfonylureas during 365 days before the event. We also analyzed the effects of the accumulative dosage of oral hypoglycemic agents (OHAs) in the above 2 models.esults A total of 37290 eligible patients were included in the cohort during 2001 to 2007. The mean age of the cohort was 55.9±14.4 years (mean±SD); 51.2% were male. There were 28340 patients in SU group and 8950 in Non-SU group. The mean age of both groups was 56.6±13.17 years (mean±SD) and 53.7±17.4 years respectively. The male patients were 54.2% in SU group and 41.7% in Non-SU group. After the index date, the proportion of prescription of antidiabetic and CV medications in SU group was significant higher than Non-SU group. And the similar condition was also found in GLY group and Non-GLY group. Aftter adjusting the related confounding factors, the exposure of sulfonylureas during 30 days before MI events was not associated with the occurance of MI events.nd there was a trend of increased risk for the patients who exposed sulfonylureas during 365 days before MI events (HR: 1.15, 95%CI: 0.99-1.32, p-value: 0.0598). If we analyzed individual sulfonylurea in the 365-day model, it was found that the HR of gliclazide was 1.2 (95% CI: 1.04-1.39, p-value:0.012). In the analysis of HF events, the variable of sulfonylureas was not significant in the model of 30 days before HF events, and the results were similar in the 365-day model. When seperating the individual sulfonylureas, the HR of gliquidone was 2.08 (95% CI: 1.11-3.38, p-vaule: 0.022). In IS events, the exposure of sulfonylureas during 30 days before IS event was associated with decreased risk, especially for gliclazide and glimepiride. But the protective effect did not exist in the 365-day model. Interestingly, the exposure of glyburide during 365 days before IS events could increase the risk of IS events.onclusion In our findings, the demographic characteristics and the prescription of antidiabetic and CV durgs were significant different in SU group and Non-SU group. And the prescription patterns in GLY group and Non-GLY group was different. Moreover, patients who exposed sulfonylureas during 30 days or 365 days were not at elevated risk of MI event. But we found the individual one, gliclazide, would be associated with higher risk of MI events in the past 1 year. In HF event, we only found the association between gliquidone and increased risk of hospitalization for CHF when exposing 1 year before. Lastly, sulfonylureas would provide protective effects on ischemic stroke in short-term or long-term exposure, especially gliclazide and glimepiride. But the protection in the period as long as 365 days might be balanced by glyburide. The results in the present study indicated that the impact on CV system of individual sulfonylureas were different, we recommend that the further studies might be designed to explore the issue more deeply.
Subjects
sulfonylurea
type 2 diabetes
cardiovascular risk
SDGs
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