Association of smoking and concomitant metformin use with cardiovascular events and mortality in people newly diagnosed with type 2 diabetes

Abstract

Background: The cardiovascular and mortality risk in patients with incident type 2 diabetes (T2D) in relation to smoking status and concurrent use of metformin is not well known. Methods: A cohort study was performed in 82 205 incident T2D patients from the UK Clinical Practice Research Datalink. In the present study, the risks of myocardial infarction (MI), stroke, and mortality in incident T2D patients were evaluated in relation to their smoking status with and without concurrent use of metformin. Results: Over a median 5.4 years of follow-up, of patients without a history of cardiovascular disease (CVD) before a diagnosis of diabetes (n=63 166), current smokers with and without metformin had an 8% (hazard ratio [HR] 1.08; 95% confidence interval [CI] 0.81, 1.45) and 32% (HR 1.32; 95% CI 1.07, 1.65) increased risk of MI or stroke, respectively, compared with non-smokers without metformin treatment. The respective HRs (95% CI) for mortality in these patients were 0.96 (0.83, 1.11) and 1.86 (1.68, 2.07). The HR for mortality among ex-smokers with and without concurrent metformin treatment was 0.92 (95% CI 0.83, 1.11) and 1.19 (95% CI 1.10, 1.30), respectively. Similar beneficial modifiable effects of metformin among ex- and current smokers were observed in patients with CVD before diagnosis of diabetes (n=19 039). Conclusions: In T2D patients, concurrent treatment with metformin attenuates the observed higher cardiovascular and mortality risk in ex- and current smokers. In addition to smoking cessation support, treatment with metformin, particularly in ex- and current smokers, should be encouraged.