Metformin reduces risk of varicose veins in patients with type 2 diabetes

Abstract

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

Treatment of Metformin Decreases the Risk of Varicose Vein: A Mendelian Randomization Study

“…Little researches were done to seek the association between treatment of metformin and risk of varicose vein. A cohort study exhibited that metformin decreased the incidence of varicose vein in type 2 diabetes patients, which was in accordance with the result in our analysis [15]. However, the truth of causal association between metformin and varicose vein without diabetes remained unknown.…”

“…There are reports that the mechanism of metformin action might be signi cantly lessening the level of TGF-β1 expression through AMPK activation [12][13][14]. There was a retrospective study published in 2019 showed that the use of metformin decreased the incidence of varicose vein in people with type 2 diabetes [15]. However, observational studies are easily affected by confounding factors and reverse causality, so that it is di cult to con rm whether there is causal association between metformin and varicose vein [16].…”

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

“…Except for varicocele, our previous analyses supported a lower risk of all these morbidities among metformin users [ 6 7 8 11 12 15 16 ]. Although the effect of metformin on varicocele has not been studied, it is highly possible that metformin may reduce the risk of varicocele (another form of venous dilatation involving the testicles) because metformin has been shown to reduce the risk of venous diseases of varicose veins [ 9 ] and hemorrhoid [ 10 ]. Therefore, metformin may potentially have a beneficial effect on ED by targeting not only the arterial system but also the venous system and related morbidities.…”

“…Metformin exerts various beneficial effects beyond glucose lowering, including immune modulation, anti-atherosclerosis, anti-cancer, anti-aging, anti-microbia, and anti-inflammation [ 3 4 ]. Recently, by using the nation-wide database of the National Health Insurance in Taiwan, we also showed that metformin use is associated with a lower risk of hypertension [ 5 ], hospitalization for heart failure [ 6 ], hospitalization for atrial fibrillation [ 7 ], chronic obstructive pulmonary disease [ 8 ], varicose veins [ 9 ], hemorrhoid [ 10 ], dementia [ 11 12 ], nodular goiter [ 13 ], uterine leiomyoma [ 14 ], osteoporosis/vertebral fracture [ 15 ], and inflammatory bowel disease [ 16 ].…”

Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

“…As pointed out by a recent article discussed by Baker et al, up to now, "there are no data to suggest that metformin should not be initiated soon after the diagnosis of diabetes", even in the era of these novel antidiabetic drugs [56]. Our previous pharmaco-epidemiological studies conducted in Taiwan suggest that metformin not only reduces cancer risk, but also the risk of various non-malignant diseases such as hypertension [58], heart failure [59], atrial fibrillation [60], chronic obstructive pulmonary disease [61], pulmonary tuberculosis infection [62], Helicobacter pylori infection [63], varicose veins [64], acute appendicitis [65], hemorrhoids [66], dementia [67,68], nodular goiter [69], uterine leiomyoma [70], osteoporosis/vertebral fracture [71], and inflammatory bowel disease [72]. We also found that metformin ever users have a lower risk of total mortality than never users of metformin, with an estimated multivariate-adjusted hazard ratio of 0.67 (95% confidence interval: 0.64-0.69) [72].…”