Observational studyCardiovascular diabetology2025
The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study.
Observational study in Cardiovascular diabetology, 2025. The graph read 6 numbers from its abstract, feeding 6 cells of the map, but none could be read as for or against, so it casts no vote. It also reports 6 associations that do not count as treatment evidence, such as HR 0.74 (0.64 to 0.84) for all-cause mortality. Cited by 12 papers.
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.
Read, but not usablea number the graph found but could not read as for or against
Combination therapy with metformin and SGLT2 inhibitors was associated with significantly reduced risk of all-cause mortality (aHR 0.74, 95% CI 0.64-0.84), and composite kidney outcomes (aHR 0.65 95% CI 0.48-0.87) even after accounting for mortality as a competing risk (aHR 0.67; 95% CI 0.5-0.9).
Furthermore, combination therapy was associated with reduced risks of hospitalization (aHR 0.93 95% CI 0.87-0.99), severe acute kidney injury events (aHR 0.72 95% CI 0.54-0.96) and metabolic acidosis events (aHR 0.58 95% CI 0.4-0.83), compared with SGLT2 inhibitors alone.
Furthermore, combination therapy was associated with reduced risks of hospitalization (aHR 0.93 95% CI 0.87-0.99), severe acute kidney injury events (aHR 0.72 95% CI 0.54-0.96) and metabolic acidosis events (aHR 0.58 95% CI 0.4-0.83), compared with SGLT2 inhibitors alone.
Combination therapy with metformin and SGLT2 inhibitors was associated with significantly reduced risk of all-cause mortality (aHR 0.74, 95% CI 0.64-0.84), and composite kidney outcomes (aHR 0.65 95% CI 0.48-0.87) even after accounting for mortality as a competing risk (aHR 0.67; 95% CI 0.5-0.9).
Combination therapy with metformin and SGLT2 inhibitors was associated with significantly reduced risk of all-cause mortality (aHR 0.74, 95% CI 0.64-0.84), and composite kidney outcomes (aHR 0.65 95% CI 0.48-0.87) even after accounting for mortality as a competing risk (aHR 0.67; 95% CI 0.5-0.9).
Furthermore, combination therapy was associated with reduced risks of hospitalization (aHR 0.93 95% CI 0.87-0.99), severe acute kidney injury events (aHR 0.72 95% CI 0.54-0.96) and metabolic acidosis events (aHR 0.58 95% CI 0.4-0.83), compared with SGLT2 inhibitors alone.
clause the extractor read what became the number
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×all-cause mortality
No readable resultOpen 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.
Metformin×kidney outcomes
No readable resultOpen 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.
Metformin×adverse events & safety
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 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.
SGLT2 inhibitors×all-cause mortality
No readable resultOpen on the map →What to test next →13 readable studies in this cell: 5 favour the treatment, 6 find no difference, 2 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.
SGLT2 inhibitors×kidney outcomes
No readable resultOpen on the map →What to test next →13 readable studies in this cell: 10 favour the treatment, 1 find no difference, 2 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.
SGLT2 inhibitors×adverse events & safety
No readable resultOpen on the map →What to test next →38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 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
12 citing papers in PubMed.
- Evaluating Cost-Effectiveness in Relation to the Supporting Clinical Evidence Across the Type 2 Diabetes Continuum: A Review of Metformin and SGLT2is.Advances in therapy · 2026Review
- Carnitine dysregulation in diabetic kidney disease: from pathogenic mechanism to precision biomarker.Journal of translational medicine · 2026Review
- AMPK is dispensable for physiological podocyte and glomerular functions but prevents glomerular fibrosis in experimental diabetes.Cell death discovery · 2026Article
- Prognostic impact of metformin in diabetic patients undergoing a percutaneous coronary intervention (PCI): protective effect is modified by procedural complexity.Cardiovascular diabetology · 2026 · on this mapObservational
- Old Drug, New Science: Metformin and the Future of Pharmaceutics.Pharmaceutics · 2026Review
- Polyphyllin II attenuates renal fibrosis in diabetic kidney disease partly through regulation of autophagy and PI3K/AKT/mTOR signaling.Frontiers in pharmacology · 2026Article
- Clinical efficacy, safety, and predictors of treatment response to SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a retrospective comparative study.Frontiers in endocrinology · 2026Article
- Efficacy and safety of metformin versus empagliflozin on chronic kidney disease progression (MET-EMPA-CKD): a randomized controlled trial.Diabetology & metabolic syndrome · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- Impact of sodium-glucose transport protein-2 (SGLT2) inhibitors on the inflammasome pathway in acute myocardial infarction in type 2 diabetes mellitus: a comprehensive review.Cardiovascular diabetology · 2025Review
- Article
- The multifaceted role of macrophages in kidney physiology and diseases.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundSelecting the optimal first-line therapy for type 2 diabetes is essential for achieving glycemic control and providing cardio-renal protection, though the combined benefits of metformin with SGLT2 inhibitors, remain uncertain.
methodsThis retrospective cohort study analyzed data from Clalit Health Services (2016-2021), to compare outcome in adults with type 2 diabetes treated with SGLT2 inhibitors alone versus in combination with metformin. Propensity score matching was applied to balance baseline characteristics between groups. Primary outcomes were a composite kidney outcome (40% decline in eGFR, or progression to ESRD), and all-cause mortality. Safety outcomes included hospitalizations, acute kidney injury and metabolic acidosis.
resultsThe study included 45,545 patients, with 6774 patients in each group following propensity score matching. The median follow-up time was 1166 days. Combination therapy with metformin and SGLT2 inhibitors was associated with significantly reduced risk of all-cause mortality (aHR 0.74, 95% CI 0.64-0.84), and composite kidney outcomes (aHR 0.65 95% CI 0.48-0.87) even after accounting for mortality as a competing risk (aHR 0.67; 95% CI 0.5-0.9). Furthermore, combination therapy was associated with reduced risks of hospitalization (aHR 0.93 95% CI 0.87-0.99), severe acute kidney injury events (aHR 0.72 95% CI 0.54-0.96) and metabolic acidosis events (aHR 0.58 95% CI 0.4-0.83), compared with SGLT2 inhibitors alone.
conclusionsPatients receiving combination therapy with metformin and SGLT2 inhibitors showed significantly reduced risks of kidney disease progression and mortality compared to those treated with SGLT2 inhibitors alone. These findings support the use of metformin with SGLT2 inhibitors as a first-line treatment strategy for type 2 diabetes irrespective of glycemic control or cardio-renal risk factors.
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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.