ArticleDiabetes2000
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Article in Diabetes, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 389 papers, 5 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.
Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.
Effectiveness of the Treatment With Dapagliflozin and Metformin Compared to Metformin Monotherapy for Weight Loss on Diabetic and Prediabetic Patients With Obesity Class III
Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly
A Phase II, Open Label Assessment of Neoadjuvant Intervention With Metformin Against Tumour Expression of Signaling
Who cites it
389 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,045 citations in OpenAlex.
- Glucagon-like peptide-1 receptor agonist-based regimens compared with metformin-based regimens for preventing cardiovascular disease in adults with type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2026Pooled it
- Metformin use is associated with a reduced risk of cognitive impairment in adults with diabetes mellitus: A systematic review and meta-analysis.Frontiers in neuroscience · 2022Pooled it
- The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021 · on this mapPooled it
- Effect of Chronic Exercise Training on Blood Lactate Metabolism Among Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Frontiers in physiology · 2021Pooled it
- Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes.The Cochrane database of systematic reviews · 2018Pooled it
- Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2024Trial
- Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes.Diabetologia · 2019Trial
- Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.Aging cell · 2019Trial
- Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes.JCI insight · 2018Trial
- A randomized, placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin.BMC endocrine disorders · 2017 · on this mapTrial
- Metformin and longevity (METAL): a window of opportunity study investigating the biological effects of metformin in localised prostate cancer.BMC cancer · 2017Trial
- Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance.The Journal of clinical investigation · 2017Trial
- Repurposing Metformin to Promote Fracture Callus Maturation via AMPK-Driven Metabolic Activation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Metformin lowers blood glucose by targeting intestinal mitochondrial complex I.Nature metabolism · 2026Article
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Synergistic antidiabetic efficacy of dorzolamide and metformin: HPTLC quantification and biological evaluation.Scientific reports · 2026Article
- Personalized Diabetes Therapy Part 2-Individual Diabetes Treatment (Standard of Care Plus, SOC+).Journal of personalized medicine · 2026Review
- Effect of Metformin on the Risk of Post-COVID-19 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Perioperative metformin use in noncardiac surgery: moving beyond precautionary discontinuation.Korean journal of anesthesiology · 2026Article
329 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
11 authors at 1 institution in 1 country.
Funding
Abstract
To examine the mechanism by which metformin lowers endogenous glucose production in type 2 diabetic patients, we studied seven type 2 diabetic subjects, with fasting hyperglycemia (15.5 +/- 1.3 mmol/l), before and after 3 months of metformin treatment. Seven healthy subjects, matched for sex, age, and BMI, served as control subjects. Rates of net hepatic glycogenolysis, estimated by 13C nuclear magnetic resonance spectroscopy, were combined with estimates of contributions to glucose production of gluconeogenesis and glycogenolysis, measured by labeling of blood glucose by 2H from ingested 2H2O. Glucose production was measured using [6,6-2H2]glucose. The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 +/- 0.05 vs. 0.36 +/- 0.03 mmol x m(-2) min(-1), P < 0.0001). Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002). The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 +/- 0.03 vs. 0.18 +/- 0.03 mmol x m(-2) min(-1) and metformin reduced that rate by 36% (to 0.38 +/- 0.03 mmol x m(-2) x min(-1), P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 +/- 0.04 mmol m(-2) x min(-1), which decreased by 33% after metformin treatment (0.28 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0002). There was no glycogen cycling in the control subjects, but in the diabetic subjects, glycogen cycling contributed to 25% of glucose production and explains the differences between the two methods used. In conclusion, patients with poorly controlled type 2 diabetes have increased rates of endogenous glucose production, which can be attributed to increased rates of gluconeogenesis. Metformin lowered the rate of glucose production in these patients through a reduction in gluconeogenesis.
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What Socratic 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 Socratic graph.