ReviewNature reviews. Endocrinology2019
Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus.
Review in Nature reviews. Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07760883 (Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status), which is not on this map. Cited by 337 papers, 2 of them syntheses 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.
Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status
Who cites it
337 citing papers in PubMed, 2 syntheses or guidelines pooled it, 652 citations in OpenAlex.
- Non-oncologic to oncologic drug: A systematic review of drug repurposing in cancer.Cancer chemotherapy and pharmacology · 2025Pooled it
- Hypoglycemic agents and incidence of pancreatic cancer in diabetic patients: a meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Circulating Profiles of the Bile Acid Metabolomics in Patients With Polycystic Ovary Syndrome Treated With Metformin or Canagliflozin.Pharmacotherapy · 2026Trial
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- The nephroprotective effect of metformin with cisplatin in bladder cancer: randomized clinical trial.International urology and nephrology · 2025Trial
- Metformin protects podocytes by inhibiting the MAPK14-SLC7A11-GPX4 axis and dysregulation of fatty acid metabolism.Diabetologia · 2026Article
- Prostaglandin E2-mediated aging microenvironment fuels pathogenic fibrosis in cesarean section scar defect.EMBO molecular medicine · 2026Article
- Maternal metformin treatment in obese pregnant dams normalizes neonatal sensory-motor reflexes.Molecular and cellular pediatrics · 2026Article
- Article
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Glycation at the Gate: A Brain Endothelial Glycocalyx Model and Therapeutic Roadmap for Alzheimer's Disease.Biomedicines · 2026Article
- Defined Natural Products as Adjunctive Therapies: Evidence-Gated Polypharmacology Across Molecular Targets, Human Exposure, Clinical Signals, and Safety Boundaries.International journal of molecular sciences · 2026Review
- Beyond Diabetes: Continuous Glucose Monitoring as a Candidate Precision Tool for Cardiovascular Prevention and Healthy Longevity-A Hypothesis-Generating Narrative Review.Medicina (Kaunas, Lithuania) · 2026Review
- Metformin Partially Attenuates Simvastatin-Induced Myotoxic Responses in C2C12 Myotubes Through Metabolic Adaptation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Supra-additive neuroprotective effects of berberine-metformin combination in diabetic encephalopathy: Chou-Talalay synergy quantification, AMPK-Nrf2 axis modulation, and pharmacokinetic verification.Metabolic brain disease · 2026Article
- Copper dysregulation in cardiometabolic disease: copper deficiency versus cuproptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Toxicological profile of anti-diabetic drugs and emerging measures to reduce the toxic burden.Toxicology reports · 2026Review
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Regulatory Effects and Mechanisms of Electromagnetic Low-Energy Shock Wave Therapy on Blood Glucose in Type 2 Diabetic Rats.Biology · 2026Article
- Article
277 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite its position as the first-line drug for treatment of type 2 diabetes mellitus, the mechanisms underlying the plasma glucose level-lowering effects of metformin (1,1-dimethylbiguanide) still remain incompletely understood. Metformin is thought to exert its primary antidiabetic action through the suppression of hepatic glucose production. In addition, the discovery that metformin inhibits the mitochondrial respiratory chain complex 1 has placed energy metabolism and activation of AMP-activated protein kinase (AMPK) at the centre of its proposed mechanism of action. However, the role of AMPK has been challenged and might only account for indirect changes in hepatic insulin sensitivity. Various mechanisms involving alterations in cellular energy charge, AMP-mediated inhibition of adenylate cyclase or fructose-1,6-bisphosphatase 1 and modulation of the cellular redox state through direct inhibition of mitochondrial glycerol-3-phosphate dehydrogenase have been proposed for the acute inhibition of gluconeogenesis by metformin. Emerging evidence suggests that metformin could improve obesity-induced meta-inflammation via direct and indirect effects on tissue-resident immune cells in metabolic organs (that is, adipose tissue, the gastrointestinal tract and the liver). Furthermore, the gastrointestinal tract also has a major role in metformin action through modulation of glucose-lowering hormone glucagon-like peptide 1 and the intestinal bile acid pool and alterations in gut microbiota composition.
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What OpenQuestion holds
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 OpenQuestion graph.