Comparative Safety and Effectiveness of Metformin in Patients With Diabetes Mellitus and Heart Failure
Bibliographic record
Abstract
BACKGROUND: There is an ongoing controversy regarding the safety and effectiveness of metformin in the setting of heart failure (HF). Therefore, we undertook a systematic review of the trial and nontrial evidence for metformin in patients with diabetes mellitus and HF. METHODS AND RESULTS: We conducted a comprehensive search for controlled studies, evaluating the association between metformin and morbidity and mortality in people with diabetes mellitus and HF. Two reviewers independently identified citations, extracted data, and evaluated quality. Risk estimates were abstracted and pooled where appropriate. As measures of overall safety, we examined all-cause mortality and all-cause hospitalizations. Nine cohort studies were included; no randomized controlled trials were identified. Most (5 of 9) studies were published in 2010 and were of good quality. Metformin was associated with reduced mortality compared with controls (mostly sulfonylurea therapy): 23% versus 37% (pooled adjusted risk estimates: 0.80; 0.74-0.87; I(2)=15%; P<0.001). No increased risk was observed for metformin in those with reduced left ventricular ejection fraction (mortality pooled adjusted risk estimate: 0.91; 0.72-1.14; I(2)=0%; P=0.34), nor in those with HF and chronic kidney disease (pooled adjusted risk estimate: 0.81; 0.64-1.02; P=0.08). Metformin was associated with a small reduction in all-cause hospitalizations (pooled adjusted risk estimate: 0.93; 0.89-0.98; I(2)=0%; P=0.01). Metformin was not associated with increased risk of lactic acidosis. CONCLUSIONS: The totality of evidence indicates that metformin is at least as safe as other glucose-lowering treatments in patients with diabetes mellitus and HF and even in those with reduced left ventricular ejection fraction or concomitant chronic kidney disease. Until trial data become available, metformin should be considered the treatment of choice for patients with diabetes mellitus and HF.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.051 | 0.136 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.012 |
| Bibliometrics | 0.006 | 0.004 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".