Metformin Versus Empagliflozin: Impact on Chronic Kidney Disease Progression

The MET-EMPA-CKD trial found that both metformin and empagliflozin significantly slowed decline in estimated glomerular filtration rate (eGFR) versus standard care over 12 months, addressing an urgent need for renoprotective strategies in moderate chronic kidney disease (CKD).

In a 12‑month randomized controlled trial, 120 patients with moderate CKD were randomized to metformin 1,000 mg/day, empagliflozin 10 mg/day, or standard‑care control, with the primary endpoint of eGFR change. Both active arms significantly slowed eGFR decline versus control (adjusted mean differences: metformin +8.91 ± 1.92 mL/min/1.73 m2, p<0.001; empagliflozin +5.10 ± 1.89 mL/min/1.73 m2, p=0.03).

Secondary renal markers such as urine albumin‑to‑creatinine ratio (uACR) shifted favorably in both arms, and the randomized design with consistent direction of effect supports internal validity.

Exploratory subgroup analyses suggested possible heterogeneity: metformin’s eGFR‑preserving effect appeared stronger in non‑diabetic CKD patients than in those with diabetes. . The pattern was concordant with intermediate biomarker changes (including TGF‑β1 and autophagy markers), which supports a mechanistic hypothesis of glycemia‑independent renal protection from metformin.

Safety data were reassuring overall. Adverse‑event rates were comparable across arms; empagliflozin was associated with a predictable increase in urinary frequency. No lactic acidosis events or other new major safety signals were reported during 12 months, and routine laboratory monitoring identified no unexpected harms. The trial’s size and duration, however, limit detection of rare or late‑onset events, so larger or longer studies are needed to exclude uncommon risks.

These results broaden treatment considerations in moderate CKD and invite targeted selection based on patient phenotype and monitoring capacity.