Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study

Abstract Background To compare the rates of incident atrial fibrillation (AF), stroke, cardiovascular mortality, and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus. Methods This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1 st , 2000 and December 31 st , 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, Charlson comorbidity index, past comorbidities, and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analysis using propensity score stratification, high dimensional propensity score and inverse probability of treatment weighting were conducted. Results A total of 36228 sulphonylurea users and 72456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75-2.77; P<0.0001), stroke (HR: 3.23, 95% CI: 3.01-3.45; P<0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62-4.81; P<0.0001), and all-cause mortality (HR: 4.35, 95% CI: 3.16-4.75; P<0.0001) compared to metformin users. Similarly significant results were observed using cause-specific and subdistribution hazard models. Sensitvity analysis using other propensity score techniques also yielded higher risks in sulphonylurea users. Conclusions Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin.