ReviewDiabetes, obesity & metabolism2017
Understanding and overcoming metformin gastrointestinal intolerance.
Review in Diabetes, obesity & metabolism, 2017. 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 117 papers, 3 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.
Efficacy of Metformin Versus Sitagliptin on Benign Thyroid Nodules Size in Type 2 Diabetes: a 2-years Prospective Multicentric Study
The Effect of Multi-strain Probiotics on Gastrointestinal Symptoms in Patients With Type 2 Diabetes and Metformin Intolerance. A 32-week Prospective, Single Center, Randomized, Placebo Controlled, Cross-over Clinical Trial.
Who cites it
117 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Effect of probiotic-derived metabolites on hormonal and metabolic profiles in women with polycystic ovary syndrome: a systematic review and meta-analysis.Frontiers in cellular and infection microbiology · 2025Pooled it
- Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis with meta-regression of observational studies.BMC endocrine disorders · 2024Pooled it
- Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- Effects of Premeal Versus Postmeal Metformin Administration on Postmeal Glycemic Control in Individuals With Type 2 Diabetes Mellitus: A Randomized, 8-Week Crossover Study.Diabetes, obesity & metabolism · 2026Trial
- Trial
- The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial.Journal of neurology · 2024Trial
- A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study).Journal of diabetes research · 2024 · on this mapTrial
- Trial
- Effects of combined metformin and cabergoline versus metformin alone on ovarian and hormonal activities in Iraqi patients with PCOS and hyperprolactinemia: a randomized clinical trial.Journal of medicine and life · 2023Trial
- Metformin with Versus without Concomitant Probiotic Therapy in Newly Diagnosed Patients with Type 2 Diabetes or Prediabetes: A Comparative Analysis in Relation to Glycemic Control, Gastrointestinal Side Effects, and Treatment Compliance.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Trial
- Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Trial
- A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes.Nature communications · 2021Trial
- Leucine and Sildenafil Combination Therapy Reduces Body Weight and Metformin Enhances the Effect at Low Dose: A Randomized Controlled Trial.American journal of therapeuticsTrial
- Comparing measured and reported change in gastrointestinal symptoms after initiation of metformin treatment: a questionnaire validation study.Scandinavian journal of primary health care · 2026Article
- Article
- Article
- Integrating Peptidomics, Network Pharmacology, Molecular Docking, and In Vitro α-Glucosidase Inhibition Assays to Explore the Hypoglycemic Activity and Action Mechanisms of Chinese Yam Peptides.Foods (Basel, Switzerland) · 2026Article
- Sex differences in cardiovascular‑kidney‑metabolic syndrome: From pathogenesis to treatment response (Review).International journal of molecular medicine · 2026Review
- Efficacy and Safety ofFoods (Basel, Switzerland) · 2026Review
- Antihyperglycemic and Antioxidant Effects ofPharmaceutics · 2026Article
57 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
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first-line pharmacological option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some GI AEs associated with metformin, some patients are unable to tolerate metformin at all and it may also be difficult to convince patients to start metformin again after a bout of GI AEs. Despite this clinical importance, the underlying mechanisms of the GI intolerance associated with metformin are poorly known. In the present review, we discuss: the epidemiology of metformin-associated GI intolerance and its underlying mechanisms; genotype variability and associated factors affecting metformin GI intolerance, such as comorbidities, co-medications and bariatric surgery; clinical consequences and therapeutic strategies to overcome metformin GI intolerance. These strategies include appropriate titration of immediate-release metformin, use of extended-release metformin, the promise of delayed-release metformin and gut microbiome modulators, as well as alternative pharmacological therapies when metformin cannot be tolerated at all. Given the available data, all efforts should be made to maintain metformin before considering a shift to another drug therapy.
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.