Pharmacological Mechanisms and Emerging Therapeutic Applications of Metformin

Metformin is one of the most widely used medications for the treatment of type 2 diabetes mellitus. Its principal glucose-lowering properties are related to the inhibition of hepatic gluconeogenesis and enhancement of peripheral insulin sensitivity. At the same time, growing data indicate that metformin might affect the intestines, gut microflora, cell metabolism, inflammation, oxidative stress, and autophagy. The present review aims to discuss the pharmacodynamics and pharmacokinetics of metformin, its clinical applications, adverse effects, and future perspectives. Special focus is made on the possible cardiovascular protective, anti-inflammatory, anticancer, anti-ageing, and polycystic ovary syndrome properties of metformin. The current evidence base allows asserting that metformin is well-established for type 2 diabetes mellitus, preventive treatment of prediabetes in selected populations, and management of certain metabolic disorders in Polycystic Ovary Syndrome (PCOS). Nevertheless, there is not enough evidence for using metformin as a means of cancer and cardiovascular disease prevention, as well as healthy ageing. Patient-specific factors, dosing, and exposure can be considered as possible causes for different results of treatment. In general, metformin is still one of the key medicines for metabolic disorder treatment, while well-conducted randomized clinical trials are required to validate its new indications and promote personalized treatment approaches.