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Role of Metformin Beyond Type 2 Diabetes
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- This review discusses the use of metformin beyond its traditional role in managing type 2 diabetes. The author covers the potential application of metformin as an adjunct therapy in conditions such as PCOS, gestational diabetes, prediabetes, and type 1 diabetes. Additionally, the role of metformin in cancer prevention (including in Li–Fraumeni syndrome), renal protection, Alzheimer's disease, and metabolic dysfunction–associated steatotic liver disease is also examined. Relevant meta-analyses are used to provide a comprehensive review of the potential uses of the drug.
- The use of metformin in managing conditions outside of type 2 diabetes shows promise. However, further studies are needed in these areas.
abstract
This abstract is available on the publisher's site.
Access this abstract nowMetformin is best known as a foundational therapy for type 2 diabetes but is also used in other contexts in clinical medicine with a number of emerging and potential indications. Many of its beneficial effects may be mediated by modest effects on weight loss and insulin sensitivity, but it has multiple other known mechanisms of action. Current clinical uses beyond type 2 diabetes include: polycystic ovarian syndrome; diabetes in pregnancy/gestational diabetes; prevention of type 2 diabetes in prediabetes; and adjunct therapy in type 1 diabetes. As metformin has been in clinical use for almost 70 years, much of the underpinning evidence for its use in these conditions is, by definition, based on trials conducted before the advent of contemporary evidence-based medicine. As a result, some of the above-established uses are 'off-label' in many regulatory territories and their use varies accordingly in different countries. Going forward, several current 'repurposing' investigational uses of metformin are also being investigated: prevention of cancer (including in Li Fraumeni syndrome), renal protection, Alzheimer's disease, metabolic dysfunction-associated steatotic liver disease and promotion of healthy ageing. Despite the longevity of metformin and its important current roles beyond type 2 diabetes in clinical medicine, it has further potential and much research is ongoing.
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Metformin beyond type 2 diabetes: Emerging and potential new indications
Diabetes Obes Metab 2024 Jul 04;[EPub Ahead of Print], JR PetrieFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Metformin’s established safety record and known metabolic benefits and efficacy in reducing glycemia have sparked significant interest in exploring alternative indications for its use. The mechanism of action of metformin remains to be fully elucidated, but numerous pathways appear to play a role in its activity. Activation of hepatic AMPK, inhibition of TOR and mitochondrial complex I, and alterations in one-carbon metabolism have all been reported in the pharmacodynamics of metformin. In the context of these mechanistic pleiotropies, there has been excitement in utilizing biguanides for the treatment of multiple disease processes, including metabolic syndrome, cancer, and aging. We have yet to generate evidence of the antineoplastic effects of metformin in large-scale human studies despite promising data in vitro and in animal models. This has also been true for metabolic dysfunction–associated steatotic liver disease and Alzheimer’s disease. Data from the DPP trial1 and follow-up studies2,3 have shown that metformin can promote modest weight loss, although the FDA did not have a separate indication for obesity treatment at the time of approval. The DPP study has also indicated that metformin can assist in preventing the progression of prediabetes; however, debate remains as to whether population-level treatment with metformin is appropriate in the context of the known efficacy of lifestyle interventions. The TAME trial will determine the impact of metformin on global aging phenotypes and will set the stage as the first trial targeting aging as a disease. Overall, the tolerability and broad mechanistic scope of metformin will continue to keep it relevant as an investigational agent for numerous diseases, while continuing to play an essential role in diabetes care.
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