Challenging Guidelines: SGLT2is Show Broad Kidney Benefits Across Diabetes Status, Albuminuria Levels, with Natalie Staplin, PhD

SGLT2 inhibitors have consistent kidney-protective benefits across a broad range of patients with chronic kidney disease (CKD) regardless of diabetes status or baseline albuminuria.

These findings, from a new meta-analysis presented by Natalie Staplin, PhD, Associate Professor of Medical Statistics at the University of Oxford, were presented at the American Society of Nephrology (ASN) Kidney Week 2025, held November 5-9, 2025, in Houston, Texas.

The analysis, which pooled data from 8 large placebo-controlled trials and included 58,816 participants with (n = 48,946) and without (n = 9870) diabetes, was conducted to help clarify ongoing questions raised by the KDIGO 2024 guidelines. Current KDIGO recommendations assign stronger grades for SGLT2 inhibitor use in patients with diabetes or albuminuria ≥200 mg/g, while providing only conditional guidance for those without diabetes or with lower albumin levels.

Staplin and colleagues found that allocation to an SGLT2 inhibitor slowed chronic eGFR decline by 57% (95%CI, 54-60) in people with diabetes and by 41% (95% CI, 33-49; P-het<0.001) in those without diabetes—a statistically significant benefit observed irrespective of albuminuria. SGLT2 inhibitor treatment also reduced kidney disease progression KDP by 32% (hazard ratio [HR], 0.68; 95% CI, 0.63-0.74), acute kidney injury by 21% (HR, 0.79; 95% CI, 0.70-0.90), all-cause mortality by 13% (HR, 0.87; 0.80-0.95), and hospitalizations by 11% (HR, 0.89; 95% CI, 0.85-0.93), with consistent effects across all subgroups.

While patients with higher baseline albuminuria derived greater absolute benefit for kidney disease progression, meaningful net benefits were observed even among those with uACR <200 mg/g, including those without diabetes. Importantly, these benefits substantially outweighed potential risks.

"If you've got a participant with low levels of albuminuria, our data supports starting them on an SGLT2 inhibitor just as much as people with higher levels of albuminuria, particularly looking at the participants without diabetes," Staplin said. "Our data support rethinking [the albumunuria threshold] and potentially removing it from the guidelines."

Staplin's disclosures include Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Reference

Staplin N, Roddick AJ, Haynes R, Herrington WG. Net Effects of SGLT2 Inhibitors by Diabetes Status and Albuminuria. Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025. #FR-OR086