The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study
Authors' conclusion
Patients 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.
Study context
- Population
- Adults with T2D treated with SGLT2i, Clalit Health Services (2016–2021)6,774 per group after matching
- Participants
- 45,545 adults
- Exposure
- SGLT2i plus metformin vs SGLT2i alone
- Combination therapyn = 6,774
- SGLT2 inhibitors alonen = 6,774reference
- Outcome
- Composite kidney outcome (40% decline in eGFR, or progression to ESRD), and all-cause mortality
- Follow-up
- Median 1166 days
Methodological detailspropensity-score matched, real-world
- Propensity-score matched
- Real-world
Main finding
As reported in the abstract
All-cause mortality; composite kidney outcome
Estimate (95% CI)
Metformin + SGLT2ivs SGLT2i alone
aHR (all-cause mortality) 0.74(0.64–0.84)
Metformin + SGLT2ivs SGLT2i alone
aHR (composite kidney outcome) 0.65(0.48–0.87)
Metformin + SGLT2ivs SGLT2i alone
aHR (composite kidney outcome, mortality as competing risk) 0.67(0.5–0.9)
Observational data: associations, not effects.
Safety
| Outcome | aHR (95% CI) | |
|---|---|---|
| HospitalizationMetformin + SGLT2ivs SGLT2i alone | 0.93 (0.87–0.99) | |
| Severe acute kidney injury eventsMetformin + SGLT2ivs SGLT2i alone | 0.72 (0.54–0.96) | |
| Metabolic acidosis eventsMetformin + SGLT2ivs SGLT2i alone | 0.58 (0.4–0.83) | |
| 0.512Adjusted hazard ratio (log scale) |
Original publication
The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study. Cardiovasc Diabetol. Published 28 February 2025. doi:10.
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