Background: Metformin’s effects on non-cancer skin diseases are rarely investigated. Objective: The aim of the study was to investigate immune-mediated (urticaria, allergic contact dermatitis, and psoriasis) and androgen-mediated (acanthosis nigricans, hidradenitis suppurativa, and acne) skin diseases associated with metformin use. Methods: Metformin initiators (n = 234,585) and non-metformin initiators (n = 125,921) within the initial 12 months of antidiabetic drug prescription during 1999–2009 were followed up until December 31, 2011. Cox regression weighted for propensity score was used to estimate hazard ratios for metformin initiators versus non-metformin initiators in intention-to-treat (ITT) and per-protocol (PP) analyses. Results: For immune-mediated skin diseases, hazard ratios were 0.930 (95% confidence interval: 0.920–0.940) and 0.930 (0.918–0.943) in ITT and PP analyses, respectively, and the hazard ratios for each specific outcome were all significantly below unity. For androgen-mediated skin diseases, the ITT and PP hazard ratios were 1.110 (1.060–1.162) and 0.990 (0.935–1.048), respectively, and all hazard ratios were not significant for each specific outcome except for acne in the ITT analysis (hazard ratio: 1.116, 95% confidence interval: 1.064–1.170). Conclusion: Metformin use is associated with a significantly lower risk of immune-mediated skin diseases but lacks a preventive effect on androgen-mediated skin diseases.

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