Addition of Metformin to SGLT2 Inhibitors Lowers Kidney Disease Risk in Diabetes Patients: Study
Researchers have found in a new study that patients receiving a combination of metformin and SGLT2 inhibitors experienced a significant reduction in kidney disease progression and mortality compared to those treated with SGLT2 inhibitors alone. This suggests that combining these medications provides greater protective benefits for kidney health. The study was published in Cardiovascular Diabetology by Agur T. and colleagues.
Although SGLT2 inhibitors are recognized for their cardio-renal protective effects, the additional benefit of combining them with metformin has been uncertain. The current retrospective cohort study, comparing outcomes in adults with type 2 diabetes treated with SGLT2 inhibitors monotherapy and with SGLT2 inhibitors plus metformin, using data from 2016 to 2021 from Clalit Health Services, sought to determine this.
The analysis involved 45,545 patients, 6,774 patients per group after propensity score matching for balanced baseline characteristics. The median follow-up was 1,166 days. The primary outcomes examined were:
• Composite kidney outcome: 40% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD).
• All-cause mortality.
• Other safety outcomes like hospitalizations, acute kidney injury (AKI), and metabolic acidosis were also assessed.
Key Findings
• Patients taking combination therapy (SGLT2 inhibitors + metformin) had 26% reduced risk of all-cause mortality (aHR 0.74; 95% CI 0.64-0.84).
• Combination therapy lowered the risk of progression of kidney disease (aHR 0.65; 95% CI 0.48-0.87), even when mortality was considered as a competing risk (aHR 0.67; 95% CI 0.5-0.9).
• Risk of hospitalization was marginally decreased with combination therapy (aHR 0.93; 95% CI 0.87-0.99).
• Acute kidney injury episodes were lower in the combination group (aHR 0.72; 95% CI 0.54-0.96).
• Metabolic acidosis episodes were 42% lower in combination therapy patients (aHR 0.58; 95% CI 0.4-0.83).
This research provides compelling evidence that metformin combination with SGLT2 inhibitors dramatically cuts mortality and development of kidney disease in type 2 diabetes. Healthcare clinicians must prioritize combination therapy to improve patient outcomes, regardless of glycemic control and pre-existing cardio-renal risk factors.
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