SynthesisCardiovascular diabetology2021
Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus.
Synthesis in Cardiovascular diabetology, 2021. The graph read 7 numbers from its abstract, feeding 2 cells of the map: it finds no clear difference in 2. Cited by 51 papers, 13 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.
Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19).
Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19).
Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19).
Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19).
Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19).
Read, but not usablea number the graph found but could not read as for or against
Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin.
Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin.
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Metformin×cardiovascular events
InconclusiveOpen on the map →What to test next →5 readable studies in this cell: 4 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Metformin×all-cause mortality
InconclusiveOpen on the map →What to test next →1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 13 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Candidate Biomarkers Linking Periodontitis with Atherosclerotic and Related Cardiovascular Phenotypes: A Systematic Review Focused on Sex-Specific Evidence.International journal of molecular sciences · 2026Pooled it
- Association of CDKAL1 gene polymorphisms variations with gestational diabetes mellitus risk in women: A case-control study and meta-analysis.BMC endocrine disorders · 2025Pooled it
- The inconclusive superiority debate of allogeneic versus autologous MSCs in treating patients with HFrEF: a systematic review and meta-analysis of RCTs.Stem cell research & therapy · 2025Pooled it
- Impact of gestational diabetes mellitus on women's sexual function: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer's disease: a meta-analysis.European journal of medical research · 2024Pooled it
- Incidence of medical device-related pressure injuries: a meta-analysis.European journal of medical research · 2024Pooled it
- Pooled it
- Efficacy and Safety of Pericapsular Nerve Group Block for Hip Fracture Surgery under Spinal Anesthesia: A Meta-Analysis.International journal of clinical practice · 2024Pooled it
- Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases.Drugs · 2022 · on this mapPooled it
- Association of vitamin A supplementation with immune-related allergic diseases: A meta-analysis.Frontiers in nutrition · 2022Pooled it
- Association of Use of Tourniquets During Total Knee Arthroplasty in the Elderly Patients With Post-operative Pain and Return to Function.Frontiers in public health · 2022Pooled it
- Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies.Frontiers in cardiovascular medicine · 2022Pooled it
- Eight Surgical Interventions for Lumbar Disc Herniation: A Network Meta-Analysis on Complications.Frontiers in surgery · 2021Pooled it
- Impact of Fixed Combination of Metformin and Pioglitazone on Insulin Resistance of Patients with Type 2 Diabetes: Results of a Randomized Open-Label Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Trial
- Type 2 Diabetes Promotes the Microglial Pyroptosis by Activating NLRP3 Inflammasome to Impede Remyelination After Spinal Cord Injury.Research (Washington, D.C.) · 2026Article
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- Effect of Tofogliflozin on Urinary Albumin-to-Creatinine Ratio vs. Metformin in Diabetic Kidney Disease: Rationale and Study Protocol of the TRUTH-DKD Trial.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Article
- Sex-specific proteomic signatures improve cardiovascular risk prediction for the general population without cardiovascular disease or diabetes.Journal of advanced research · 2026Article
- The Association Between Gamma-Glutamyl Transferase and Metabolic Syndrome and Its Components Among Adolescents Applying International Diabetes Federation (IDF) and Cook's Criteria.Endocrinology, diabetes & metabolism · 2025Article
- Association Between Size of Left Ventricle and Long-Term Cardiovascular Events.Journal of the American Heart Association · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundMetformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive.
methodsWe searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality.
resultsWe identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin.
conclusionThe combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).
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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.