ArticleThe Biochemical journal2014
Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03031821 (A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome), which is not on this map. Cited by 381 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome: The Prime Study
Who cites it
381 citing papers in PubMed, 1 synthesis or guideline pooled it, 637 citations in OpenAlex.
- Exploring multifaceted roles of metformin in therapeutic applications, mechanistic insights, and innovations in drug delivery systems across biological contexts: a systematic review.Drug delivery and translational research · 2025Pooled it
- LKB1 Loss Sensitizes Lung Tumor Spheres to Mitomet-Induced Ferroptosis, and These Effects are Enhanced by mTOR Inhibition.Molecular carcinogenesis · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Impact of metformin-based chemo-radiotherapeutic strategies on breast cancer stemness and autophagy-associated gene expression: evidence from ALDH1A1 and LC3 expression analysis.Molecular biology reports · 2026Article
- Article
- Metformin Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance.bioRxiv : the preprint server for biology · 2026Article
- Toxicological profile of anti-diabetic drugs and emerging measures to reduce the toxic burden.Toxicology reports · 2026Review
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Article
- Article
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Article
- Nebivolol suppresses glioblastoma progression via dual modulation of mitochondrial metabolism and AKT/mTOR/4EBP1 signaling axis.PLoS genetics · 2026Article
- Single-Mitochondrion ATP Profiling Directs Discovery of Targetable OXPHOS Dependency in Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Succinate dehydrogenase-deficient cancer cells have increased susceptibility to Ym155-induced DNA damage.Endocrine-related cancer · 2026Article
- A Novel Protective Strategy Against Metformin-Induced Renal Injury Involving Adenosine Triphosphate and Thiamine Pyrophosphate.International journal of molecular sciences · 2026Article
- ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC.Nature chemical biology · 2026Article
- Mammalian Respiratory Chain Complex Assemblies and Their Links to Mitochondria Stress-Induced Human Diseases.Advances in experimental medicine and biology · 2026Review
- Targeting mitofusin 1-mediated mitochondrial dynamics to suppress neuroinflammation and pyroptosis after traumatic brain injury.Burns & trauma · 2026Article
321 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the molecular interaction(s) between metformin and complex I remain uncharacterized. In the present paper, we describe the effects of five pharmacologically relevant biguanides on oxidative phosphorylation in mammalian mitochondria. We report that biguanides inhibit complex I by inhibiting ubiquinone reduction (but not competitively) and, independently, stimulate reactive oxygen species production by the complex I flavin. Biguanides also inhibit mitochondrial ATP synthase, and two of them inhibit only ATP hydrolysis, not synthesis. Thus we identify biguanides as a new class of complex I and ATP synthase inhibitor. By comparing biguanide effects on isolated complex I and cultured cells, we distinguish three anti-diabetic and potentially anti-neoplastic biguanides (metformin, buformin and phenformin) from two anti-malarial biguanides (cycloguanil and proguanil): the former are accumulated into mammalian mitochondria and affect oxidative phosphorylation, whereas the latter are excluded so act only on the parasite. Our mechanistic and pharmacokinetic insights are relevant to understanding and developing the role of biguanides in new and existing therapeutic applications, including cancer, diabetes and malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.