Trial reportDiabetes care2016
The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies.
Trial report in Diabetes care, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03039075. Cited by 161 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.
Comparison of Metformin Hydrochloride Sustained-release Tablet (DuLeNing) and Glucophage in Patients With Type 2 Diabetes
Metformin Gastrointestinal Intolerance: Measurement of Mitochondrial Complex I
A Randomized, Crossover Study Assessing the Effect of EFB0027 on Plasma Glucose and Pharmacokinetics in Subjects With Type 2 Diabetes Mellitus
A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Delayed-Release Metformin in Subjects With Type 2 Diabetes Mellitus
A Randomized, Crossover Study Assessing the Pharmacokinetics of EFB0027 Versus ETB0015 and ETB0014 in Healthy Subjects
Who cites it
161 citing papers in PubMed, 5 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2.Diabetes care · 2023Pooled it
- Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression.Human molecular genetics · 2022Pooled it
- Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials.Frontiers in endocrinology · 2022Pooled it
- Comparison of the gamma-Pareto convolution with conventional methods of characterising metformin pharmacokinetics in dogs.Journal of pharmacokinetics and pharmacodynamics · 2020Pooled it
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- Combining a diet rich in fermentable carbohydrates with metformin improves glycaemic control and reshapes the gut microbiota in people with prediabetes.Nature metabolism · 2025Trial
- Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Trial
- Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes.BMC microbiology · 2022Trial
- Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.Frontiers in cellular and infection microbiology · 2022Trial
- Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial.Diabetes care · 2021Trial
- The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial.Diabetologia · 2021Trial
- Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study.Diabetologia · 2019Trial
- Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes.JCI insight · 2018Trial
- Genetic Variants inDiabetes · 2018Trial
- Improved glycemic control with minimal systemic metformin exposure: Effects of Metformin Delayed-Release (Metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes.PloS one · 2018 · on this mapTrial
- Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.PloS one · 2018Trial
- Trial
- Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.Nature medicine · 2017Trial
101 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
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDelayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediate-release metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND
methodsStudy 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference).
resultsThe bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information.
conclusionsDissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.
Indexed as
Identifiers
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.