Beyond Glycemia: Metformin’s Anti-Inflammatory, Antioxidant, and Immunomodulatory Effects in Chronic Diseases: A Narrative Review

Document Type : Review

Author

Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

10.22038/rcm.2026.91748.1565

Abstract

Metformin (1,1-dimethylbiguanide hydrochloride) has been the most commonly prescribed blood sugar-lowering medication for over six decades and is the most important treatment for individuals newly diagnosed with type 2 diabetes mellitus (T2DM). The major action of metformin is to directly suppress hepatic gluconeogenesis and improve insulin sensitivity. However, metformin also indirectly enhances insulin secretion by increasing glucagon-like peptide-1 (GLP-1) concentration. Recent research highlights the broader therapeutic potential of metformin in chronic diseases associated with inflammation. The aim of this study is to investigate the effects of metformin beyond blood sugar reduction in chronic diseases by examining indicators related to inflammation and immunity. The anti-inflammatory and antioxidant mechanisms of metformin involve both AMP-activated protein kinase (AMPK)-dependent and -independent pathways. AMPK mediates the anti-inflammatory and antioxidant effects of metformin by regulating the activity and levels of NF-κB, NLRP3, inflammatory cytokines, NRF2, as well as oxidative and antioxidant markers. In addition, other roles of metformin that contribute to reducing the incidence of T2DM and chronic complications—including cardiovascular diseases, cerebrovascular diseases, nephropathy, retinopathy, neuropathy, autoimmune diseases, neurodegenerative diseases, and cancer—include direct inhibition of mitochondrial ROS, inhibition of mTORC1, modulation of gut microbiota, GDF15 upregulation, and regulation of innate and adaptive immunity.

Keywords

Reviews in Clinical Medicine
Volume 13, Issue 1
Volume 13, Issue 1, March 2026
May 2026
Pages 69-75

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