Metformin and Risk of Hypertension in Taiwanese Patients With Type 2 Diabetes Mellitus

Abstract

BackgroundWhether metformin use may reduce hypertension risk has not been studied. This study investigated such possibility in patients with type 2 diabetes mellitus.Methods and ResultsNewly diagnosed patients with type 2 diabetes mellitus during 1999–2005 were enrolled from the reimbursement database of the Taiwan's National Health Insurance and followed to December 31, 2011. Hypertension was defined either by a diagnosis or by a diagnosis plus the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and/or calcium channel blockers. Analyses were conducted in a propensity score matched‐pair cohort of 4810 ever users and 4810 never users. Cox proportional hazards regression model was used to estimate the hazard ratios. Results showed that when hypertension was defined by a diagnosis, 2261 never users and 1908 ever users developed hypertension. The overall hazard ratio was 0.724 (0.681–0.769) and the hazard ratios for the first (<2.0 months), second (2.0–13.0 months) and third (>13.0 months) tertiles of cumulative duration were 0.820 (0.745–0.903), 0.692 (0.634–0.756), and 0.687 (0.630–0.749), respectively. When cumulative duration of metformin therapy was treated as a continuous variable, the hazard ratio was 0.991 (0.989–0.994) for every 1‐month increment of metformin use. When hypertension was defined by a diagnosis plus the use of antihypertensive drugs, the overall hazard ratio was 0.831 (0.771–0.895), the hazard ratios for the respective tertiles were 0.868 (0.769–0.980), 0.852 (0.767–0.946), and 0.787 (0.709–0.874), and the hazard ratio was 0.994 (0.991–0.997) for every 1‐month increment of metformin use.ConclusionsA reduced risk of hypertension is observed in metformin users in a dose‐response pattern.

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

“…, enhanced endothelium-dependent vasodilatation and sympathetic nerve activity attenuation, but metformin might not have a significant impact on the third pathway involving hypertension regulation [ 30 ]. However, the potential effect of metformin on ED via the third pathway is at least partly supported by our recent observational study that showed a significant risk reduction of hypertension (hazard ratio [HR], 0.724; 95% confidence interval [CI], 0.681–0.769) in patients with T2DM who had been treated with metformin in comparison to patients who had never been treated with metformin [ 5 ]. Because hypertension is a well-recognized risk factor of atherosclerotic diseases and ED [ 31 ], an improvement in arteriogenic ED resulting from a reduced risk of hypertension and atherosclerotic diseases associated with metformin use is probable.…”

“…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].…”

Single Nucleotide Polymorphism in the 3’ Untranslated Region of PRKAA2 on Cardiometabolic Parameters in Type 2 Diabetes Mellitus Patients Who Received Metformin

“…Hypertension risk could be reduced among metformin users who are newly diagnosed with T2DM. 24 Metformin has proven blood pressure reduction in patients with T2DM compared with insulin therapy. 25 Monotherapy metformin could significantly reduce triglyceride and low-density lipoprotein cholesterol (LDL-c) levels, and enhance (high-density lipoprotein cholesterol) HDL-c. 26 The various international guidelines recommend detecting and monitoring cardiometabolic parameters in addition to HbA1c level in patients with T2DM.…”