ArticleNature2014
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 676 papers, 7 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.
Metformin Gastrointestinal Intolerance: Measurement of Mitochondrial Complex I
Effect of Adding Metformin to Insulin in Uncontrolled Diabetic Patients During the 3rd Trimester of Pregnancy on Glycemic Control, Fetal and Neonatal Outcomes ,Randomized Controlled Trial
Who cites it
676 citing papers in PubMed, 7 syntheses or guidelines pooled it, 1,265 citations in OpenAlex.
- Fasting-mimicking diets as a strategy to reprogram tumor metabolism: a systematic review.European journal of nutrition · 2026Pooled it
- Comparative analysis of glucagon-like peptide-1 receptor agonists, metformin, and inositol in improving anthropometric and metabolic outcomes in women with polycystic ovary syndrome: a network meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Multiple Therapeutic Applications of Metformin Moving Beyond Its Anti-Diabetic Role: A Systematic Review.Journal of the ASEAN Federation of Endocrine Societies · 2025Pooled it
- Harnessing probiotic-metformin synergy: targeting the gut-microbiota metabolism axis to ameliorate polycystic ovary syndrome.Frontiers in nutrition · 2025Pooled it
- Influence of Solute Carrier Family 22 Member 1 (Current diabetes reviews · 2024Pooled it
- Pooled it
- Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.World journal of surgical oncology · 2023 · on this mapPooled it
- Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.Scientific reports · 2025Trial
- Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes.Frontiers in endocrinology · 2023Trial
- Neuroregenerative implications of dimethylglyoxal (diacetyl): A reactive metabolite in diabetes and hyperglycemic stroke.Neural regeneration research · 2026Article
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Metformin protects podocytes by inhibiting the MAPK14-SLC7A11-GPX4 axis and dysregulation of fatty acid metabolism.Diabetologia · 2026Article
- Mitochondrial Metabolic Reprogramming and Skin Immune Homeostasis: From Basic Mechanisms to Therapeutic Perspectives.Immune network · 2026Review
- Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction.Problemy endokrinologii · 2026Review
- Context-Dependent Modulation of Ferroptosis by Metformin: Mechanisms, Therapeutic Implications and Open Questions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Revisiting Insulin Resistance in the Pathophysiology of Type 2 Diabetes Mellitus: A Multi-Organ Perspective.Diabetes & metabolism journal · 2026Review
- Sex-specific mitochondrial dysregulation and metformin response in Wilson disease.Scientific reports · 2026Article
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- The eternal struggle between titans: Fecal microbiota transplant (FMT) versus metformin in type 2 diabetes (T2D) gut dysmotility.Journal of advanced research · 2026Review
616 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia. For over half a century, this agent has been prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production, while increasing cytosolic redox and decreasing mitochondrial redox states. Antisense oligonucleotide knockdown of hepatic mitochondrial glycerophosphate dehydrogenase in rats resulted in a phenotype akin to chronic metformin treatment, and abrogated metformin-mediated increases in cytosolic redox state, decreases in plasma glucose concentrations, and inhibition of endogenous glucose production. These findings were replicated in whole-body mitochondrial glycerophosphate dehydrogenase knockout mice. These results have significant implications for understanding the mechanism of metformin's blood glucose lowering effects and provide a new therapeutic target for type 2 diabetes.
Indexed as
Identifiers
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.