Across 17 randomized controlled trials enrolling 29,192 patients with diabetic chronic kidney disease, SGLT2 inhibitors reduced HbA1c by 0.40%, body weight by 1.36 kg, and systolic blood pressure by 2.98 mmHg versus comparators. Yet the drugs produced no statistically significant change in eGFR (+0.25 mL/min/1.73m²) or urinary albumin-to-creatinine ratio (−31.55 mg/g), the two primary renal surrogate markers. Volume depletion adverse events were meaningfully elevated (RR 1.36), while urinary tract infection risk was not significantly increased.
The surrogate-marker null finding deserves careful framing. SGLT2 inhibitors are known to cause an acute, hemodynamically mediated eGFR dip on initiation — a transient drop that masks underlying tubulo-glomerular benefit and tends to resolve within months. Short-to-medium follow-up windows across many included trials likely captured this dip without observing the subsequent preservation trajectory documented in longer landmark trials such as CREDENCE and DAPA-CKD, which demonstrated 30–40% reductions in hard renal endpoints. The robust reductions in blood pressure and weight are themselves cardiorenal risk factors, suggesting cumulative benefit that surrogate windows simply cannot capture. The volume-depletion signal warrants clinical vigilance, particularly in older patients or those on concurrent diuretics. Overall, this meta-analysis is confirmatory rather than paradigm-shifting: it reinforces that surrogate markers alone underestimate SGLT2 inhibitor benefit in CKD and that the class remains among the most evidence-backed interventions in diabetic kidney disease.