Is gliclazide associated with a lower obesity-related cancer risk compared to other sulfonylureas? a long-term prospective cohort study

Abstract

Background: Gliclazide has been suspected to be associated with a lower obesity-related cancer risk; however, current evidence is limited by important methodologic shortcomings. This study aimed to evaluate whether gliclazide is preferred over other sulfonylureas regarding obesity-related cancer risk. Methods: In this prospective cohort study, an annual benchmarking database in Dutch primary care (Zwolle Outpatient Diabetes project Integrating Available CareZODIAC, 1998–2014) was linked to the Netherlands Cancer Registry and the Dutch Personal Record Database. Of the 71,648 patients with type 2 diabetes, we included 26,207 who used sulfonylureas and had no history of cancer or insulin use at baseline. Obesity-related cancer was defined using the latest definition of the World Cancer Research Fund. Cox regression analyses were used to estimate HRs, with both baseline sulfonylurea and cumulative exposure modeled and corrected for baseline covariates. Results: During follow-up for 167,692 person-years, there were 1,111 obesity-related cancer events. For males, the adjusted HRs [95% confidence interval (CI)] for baseline sulfonylurea compared with gliclazide were as follows: glibenclamide, 1.10 (0.92–2.69); glimepiride, 1.13 (0.68–1.84); and tolbutamide, 0.93 (0.59–1.48). For females, these were as follows: glibenclamide, 1.49 (0.72–3.13); glimepiride, 0.96 (0.59–1.54); and tolbutamide, 0.84 (0.54–1.28). The adjusted HRs (95% CI) for one more year of cumulative exposure compared with gliclazide were as follows: glibenclamide, 0.90 (0.71–1.14); glimepiride, 0.96 (0.87–1.06); and tolbutamide, 1.00 (0.92–1.09). For females, these were as follows: glibenclamide, 0.93 (0.77–1.13); glimepiride, 0.99 (0.90–1.10); and tolbutamide, 1.04 (0.96–1.13). Conclusions: Obesity-related cancer risk was comparable between gliclazide and other sulfonylureas. Impact: Gliclazide is not preferred over other sulfonylureas regarding obesity-related cancer risk.