Aim: This population-based retrospective cohort study compared the incidence of varicose veins in an unmatched cohort and a cohort of 1:1 propensity score (PS)matched pairs of ever and never users of metformin in type 2 diabetes patients.
Methods: Patients with new-onset type 2 diabetes during 1999 to 2005 were enrolled from Taiwan's National Health Insurance and followed until December 31, 2011. Analyses were conducted in an unmatched cohort of 123 710 ever users and 15 095 never users and in 15 088 PS-matched pairs of ever users and never users.Hazard ratios were estimated by Cox proportional hazards model incorporated with the inverse probability of treatment weighting using the PS. Results: New-onset varicose veins were diagnosed in 126 never users and 633 ever users in the unmatched cohort and in 126 never users and 80 ever users in the matched cohort. The respective incidences were 191.36 and 110.04 per 100 000 person-years in the unmatched cohort and 191.41 and 115.81 per 100 000 person-years in the matched cohort. The hazard ratio for ever versus never users in the unmatched cohort was 0.57 (95% confidence interval, 0.47-0.69) and was 0.60 (0.45-0.80) for the matched cohort. In the unmatched cohort, the hazard ratios for the first, second, and third tertiles of cumulative duration were 1.03 (0.83-1.28), 0.55 (0.44-0.69), and 0.29 (0.23-0.37), respectively. The respective hazard ratios in the matched cohort were 0.97 (0.65-1.43), 0.79 (0.55-1.15), and 0.24 (0.13-0.42). Conclusion: Metformin use is associated with a lower risk of varicose veins in patients with type 2 diabetes. KEYWORDS diabetes mellitus, metformin, Taiwan, varicose veins 1 | INTRODUCTION Varicose veins often start from the lower extremities and are always diagnosed by physicians at a stage with clinical manifestations of oedema, engorging and tortuous veins, or venous ulceration. It affects more women than men in most populations. 1 An early survey in Fin-land showed that the prevalence rates of physician-diagnosed varicose veins were 25% in women and 7% in men. 2 However, reported prevalence rates varied remarkably in different studies, from less than 1% to 73% in women and 2% to 56% in men. 1 The Finnish study identified risk factors such as age, body height, body mass index, standing at work, high socio-economic status, and the numbers of births (in women). 2 Interestingly, diabetes was negatively associated with varicose veins in this early study. 2 The positive association between varicose veins and obesity has been confirmed in a recent study, 3 but the negative association with diabetes has not gained much attention and has been rarely investigated in other epidemiological studies.Because obesity and diabetes are both characterized by increased