Pharmacokinetics and Mechanism of Action of Metformin Pharmacokinetics Furthermore, the immunological mechanisms exerted by metformin will be explored as well as its potential relevance in the treatment of autoimmune diseases. In addition to recent evaluation of the metabolic and immunological roles of metformin ( 7), this article will appraise current preclinical and clinical data regarding the effect of metformin on individual cells of the immune system. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin. Notably, emerging in vivo and in vitro evidences suggest that metformin can exhibit immune-modulatory features ( 6, 7).
Nose infection side effect of metformin trial#
This fascinating hypothesis is currently being tested through the ongoing Targeting Aging with Metformin study, a placebo-controlled trial ( 5) aimed at investigating the potential role of metformin in delaying the onset of aging-associated diseases. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice ( 4), provided the basis for defining metformin as a potential antiaging molecule ( 5). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects ( 3). However, the exact pharmacodynamic properties have been elusive for many years still remaining a matter of debate ( 2). Indeed, metformin lowers both fasting and post-prandial glucose levels by inhibiting hepatic glucose production, reducing intestinal glucose absorption, and improving glucose uptake and utilization by peripheral tissues. Metformin ( dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect ( 1).
Since its discovery more than 50 years ago, metformin represents a worldwide milestone in treatment of patients with type 2 diabetes (T2D). In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. Moreover, emerging in vivo and in vitro evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential antiaging molecule. Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. Metformin ( dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect. 8Department of Medical Sciences, Clinica Medica Unit, University of Ferrara, Ferrara, Italy.7Department of Nuclear Medicine, IRCCS Neuromed, Pozzilli, Italy.6Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy.5Basilicata Ricerca Biomedica (BRB) Foundation, Potenza, Italy.
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