Metformin plus SGLT2 inhibitors may lower kidney risk, 35%, and 26% mortality - compared with SGLT2i alone

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Metformin plus SGLT2 inhibitors may lower kidney risk, 35%, and 26% mortality – compared with SGLT2i alone

The addition of metformin to SGLT2 inhibitors was associated with reductions in kidney disease progression and mortality in patients with type 2 diabetes, according to a study in the journal Cardiovascular Diabetology.

Based on data for 45,545 patients, combination therapy lowered the risk of progression of kidney disease by 35% and reduced the risk of all-cause mortality by 26% compared with SGLT2 inhibitors alone.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11871758/

The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study

Timna Agur ^1,2,^✉, Tali Steinmetz ^1,2, Shira Goldman ^1,2, Boris Zingerman ^1,2, Dana Bielopolski ^1,2, Eviatar Nesher ^2,3, Ittai Fattal ^1,2, Eshcar Meisel ^1,2, Benaya Rozen-Zvi ^1,2

Abstract

Background

Selecting 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.

Methods

This 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. P rimary 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.

Results

The 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.

Conclusions

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.

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