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

BACKGROUND: Whether metformin use may reduce hypertension risk has not been studied. This study investigated such possibility in patients with type 2 diabetes mellitus. METHODS AND RESULTS: Newly 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. CONCLUSIONS: A reduced risk of hypertension is observed in metformin users in a dose‐response pattern.