Repurposing metformin: an old drug with new tricks in its binding pockets
Open accessAbstract
Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world yet it also presents a grave challenge: as more people survive into later life, more also experience the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective novel treatments are still lacking. Alternative drug development strategies are now being explored, such as the repurposing of existing drugs used to treat other diseases. This can save a considerable amount of time and money since the pharmacokinetics, pharmacodynamics and safety profiles of these drugs are already established, effectively enabling preclinical studies to be bypassed. Metformin is one such drug currently being investigated for novel applications. The present review provides a thorough and detailed account of our current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide-protein interactions. It also focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function. Research in this area holds the key to solving many of the mysteries of our current understanding of drug action and concerted effects to provide sustained and long-life health.
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Metformin reduces hepatic glucose production and increases insulin sensitivity by activating AMPK, although several AMPK-independent mechanisms have been proposed.
“Metformin is a biguanide and reduces hepatic glucose production and increases insulin sensitivity by activating AMPK, although several AMPK-independent mechanisms have been proposed [reviewed in Pryor and Cabreiro (246)].”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [246]
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- Authors
- Pryor, R., & Cabreiro, F.
- Affiliations
- Institute of Structural and Molecular Biology (GB)
- Corresponding author
- Pryor, Rosina
- Cabreiro, Filipe
- ORCID
- Cabreiro, Filipe
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2015-10-16
- Volume
- 471
- Issue
- 3
- Pages
- 307-322
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC4613459
- OpenAlex
- W2179359265
- Cited by
- 280
- References
- 173
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 32 · 2020: 32 · 2019: 31 · 2018: 40 · 2017: 36 · 2016: 29 · 2014: 1
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (102531, 102531/Z/13/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, drug repurposing, biguanides, protein-ligand interactions, molecular pharmacology, signalling mechanisms, gut microbiota, age-related diseases, type 2 diabetes, cardiovascular disease, cancer
- MeSH terms
- Biguanides, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Metformin, Neoplasms, Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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