Observational studyAmerican journal of kidney diseases : the official journal of the National Kidney Foundation2025
Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study.
Observational study in American journal of kidney diseases : the official journal of the National Kidney Foundation, 2025. The graph read 4 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 3 papers.
What it found
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Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR, 1.34 [95% CI, 1.08-1.67]; MACE: HR, 1.04 [95% CI, 0.81-1.33]).
Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR, 1.34 [95% CI, 1.08-1.67]; MACE: HR, 1.04 [95% CI, 0.81-1.33]).
Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]), and the incidence of MACE was similar between both strategies (HR, 1.05 [95% CI, 0.88-1.26]).
Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]), and the incidence of MACE was similar between both strategies (HR, 1.05 [95% CI, 0.88-1.26]).
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Where it lands on the map
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What it adds to each cell
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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.
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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.
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Who cites it
3 citing papers in PubMed.
- Metformin Use and Clinical Outcomes in Very Elderly Patients with Type 2 Diabetes and Chronic Kidney Disease.Medicina (Kaunas, Lithuania) · 2026Observational
- Impact of Different Glomerular Filtration Rate Equations on Metformin Eligibility in Patients with Diabetes Mellitus and Chronic Kidney Disease.Journal of clinical medicine · 2026Article
- Metformin Alone and in Combinations Alter the Methylation Patterns ofEndocrine, metabolic & immune disorders drug targets · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
RATIONALE &
objectiveDespite a lack of supporting evidence, current guidance recommends against the use of metformin in people with advanced kidney impairment. This observational study compared the outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR]<30mL/min/1.73m STUDY
designNationwide observational cohort study. SETTING &
participantsAll adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019. EXPOSURE: Stopping versus continuing metformin within 6 months following incident stage 4 CKD. OUTCOME: Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE). ANALYTICAL APPROACH: Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.
resultsIn a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before April 30, 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within 6 months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]), and the incidence of MACE was similar between both strategies (HR, 1.05 [95% CI, 0.88-1.26]). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR, 1.34 [95% CI, 1.08-1.67]; MACE: HR, 1.04 [95% CI, 0.81-1.33]). LIMITATIONS: Residual confounding.
conclusionsThe continued use of metformin may be appropriate when eGFR falls below 30mL/min/1.73m PLAIN-LANGUAGE SUMMARY: Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of evidence. It is therefore currently unclear how the decision to stop versus continue metformin in patients who reach stage 4 CKD impacts their risk of mortality and cardiovascular events. This study showed that stopping metformin after reaching stage 4 CKD was associated with reduced survival that did not appear to be mediated by an increase in adverse cardiovascular outcomes. These findings may support the continued use of metformin in patients with advanced kidney impairment, but further research is needed to confirm these observations.
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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.