Glibenclamide-related excess in total and cardiovascular mortality risks: Data from large Ukrainian observational cohort study

Abstract 

Objective

To compare mortality risks among type 2 diabetes (T2D) patients being treated with glibenclamide, gliclazide, or glimepiride.

Methods

Retrospective observational cohort studies of primary care-based diabetes register were carried out. Risk of total and cardiovascular (CVD) mortality was evaluated in cohort of T2D patients that were treated with either glibenclamide (n=50341), glimepiride (n=2479) or gliclazide (n=11368). Cox regression was used for multifactor evaluation. A cross-sectional evaluation of oral anti-diabetic drug (OAD) structure for 2005 and 2007 was also performed, as well as age at the time of death was compared in the timeframe between 2002 and 2007.

Results

Total mortality was lower for gliclazide and glimepiride, vs. glibenclamide cohort: HRs 0.33 (95% CI 0.26–0.41), p<0.001 and 0.605 (95% CI 0.413–0.886), p<0.01 respectively. CVD mortality risk reduction vs. glibenclamide was significant only in gliclazide cohort: 0.29 (95% CI 0.21–0.38), p<0.001. Glibenclamide prescriptions had changed from 64.0% (95% CI 63.5–64.5) to 59.5% (95% CI 9.7–10.4). Age at the time of death for OAD-treated patients increased by 6.27 (95% CI 3.67–8.87)yrs, p<0.001.

Conclusion

Glibenclamide treatment of T2D is associated with greater risk of all-cause mortality, vs. gliclazide or glimepiride treatment, and CVD mortality, vs. gliclazide treatment.

Abbreviations: T2D, type 2 diabetes, OAD, oral anti-diabetic drugs, SINADIAB, System of Diabetes Mellitus Supervision in Ukraine, PC, primary care, CVD, cardiovascular disease, ICD, International Classification of Diseases, BMI, body mass index, BP, blood pressure

Keywords: Glibenclamide, Gliclazide, Glimepiride, Cardiovascular disease, Mortality, Type 2 diabetes