Trial reportJCI insight2018
Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes.
Trial report in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02050074. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The Role of Metformin and Colesevelam in Human GLP-1 Secretion
Open the trial in the graphWho cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Intervening Early in the Cardiovascular-Kidney-Metabolic Syndrome: Expert Recommendations from the United Arab Emirates on the Management of Prediabetes.Vascular health and risk management · 2026Guideline
- Combining a diet rich in fermentable carbohydrates with metformin improves glycaemic control and reshapes the gut microbiota in people with prediabetes.Nature metabolism · 2025Trial
- Differential effects of imeglimin and metformin on insulin and incretin secretion-An exploratory randomized controlled trial.Diabetes, obesity & metabolism · 2025Trial
- Trial
- Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes.Diabetes · 2024Trial
- Effects of different doses of exercise and diet-induced weight loss on beta-cell function in type 2 diabetes (DOSE-EX): a randomized clinical trial.Nature metabolism · 2023Trial
- Metformin upregulates mitophagy in patients with T2DM: A randomized placebo-controlled study.Journal of cellular and molecular medicine · 2020Trial
- Revisiting Insulin Resistance in the Pathophysiology of Type 2 Diabetes Mellitus: A Multi-Organ Perspective.Diabetes & metabolism journal · 2026Review
- Metformin in Diabetes and Beyond: Therapeutic Mechanisms, Lactic Acidosis, Organ-Specific Effects, and Nanotechnology-Based Delivery Strategies.Current medical science · 2026Review
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Glucagon-like peptide-1 receptor agonists are associated with reduced abdominal aortic aneurysm-related events.Journal of vascular surgery · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Pathogenesis and intervention strategies for metabolic dysfunction-associated fatty liver disease from the perspective of the gut-microbiota-liver axis.Frontiers in immunology · 2026Review
- Reframing metformin as a gut-targeted glucose-lowering therapy: Mechanistic insights and translational relevance.Molecular metabolism · 2025Article
- The Role of the Gut Microbiome Dysbiosis in Metabolic Dysfunction: A Mini Review.Healthcare (Basel, Switzerland) · 2025Review
- Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice.Clinical and translational medicine · 2025Article
- Gastric Emptying Delay with Pre-Meal Administration of Metformin and Anagliptin in Type 2 Diabetes: Effects on Postprandial Glucose and Triglyceride Levels in a Two-Case Report.The American journal of case reports · 2025Article
- Article
- Novel mechanism whereby metformin improves glucose homeostasis: TXNIP-GLUT1 axis modulation enhances intestinal glucotonic effects.Experimental & molecular medicine · 2025Article
17 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
20 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin reduces plasma glucose and has been shown to increase glucagon-like peptide 1 (GLP-1) secretion. Whether this is a direct action of metformin on GLP-1 release, and whether some of the glucose-lowering effect of metformin occurs due to GLP-1 release, is unknown. The current study investigated metformin-induced GLP-1 secretion and its contribution to the overall glucose-lowering effect of metformin and underlying mechanisms in patients with type 2 diabetes.
methodsTwelve patients with type 2 diabetes were included in this placebo-controlled, double-blinded study. On 4 separate days, the patients received metformin (1,500 mg) or placebo suspended in a liquid meal, with subsequent i.v. infusion of the GLP-1 receptor antagonist exendin9-39 (Ex9-39) or saline. During 240 minutes, blood was sampled. The direct effect of metformin on GLP-1 secretion was tested ex vivo in human ileal and colonic tissue with and without dorsomorphin-induced inhibiting of the AMPK activity.
resultsMetformin increased postprandial GLP-1 secretion compared with placebo (P = 0.014), and the postprandial glucose excursions were significantly smaller after metformin + saline compared with metformin + Ex9-39 (P = 0.004). Ex vivo metformin acutely increased GLP-1 secretion (colonic tissue, P < 0.01; ileal tissue, P < 0.05), but the effect was abolished by inhibition of AMPK activity.
conclusionsMetformin has a direct and AMPK-dependent effect on GLP-1-secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin's glucose-lowering effect and mode of action.
trial registrationNCT02050074 (https://clinicaltrials.gov/ct2/show/NCT02050074).
fundingThis study received grants from the A.P. Møller Foundation, the Novo Nordisk Foundation, the Danish Medical Association research grant, the Australian Research Council, the National Health and Medical Research Council, and Pfizer Inc.
Indexed as
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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.