Effects of SGLT2 inhibitors across the spectrum of albuminuria in cardiovascular-kidney-metabolic conditions: A pooled analysis of randomised trials

João Pedro Ferreira; Pedro Marques; Stefan D Anker; Javed Butler; Gerasimos Filippatos; Abhinav Sharma; Francisco Vasques-Nóvoa; Luís Mendonça; João Sérgio Neves; Milton Packer; Faiez Zannad

doi:10.1111/dom.70289

Effects of SGLT2 inhibitors across the spectrum of albuminuria in cardiovascular-kidney-metabolic conditions: A pooled analysis of randomised trials

Diabetes Obes Metab. 2025 Nov 10. doi: 10.1111/dom.70289. Online ahead of print.

Authors

João Pedro Ferreira^{1

2}, Pedro Marques^{1

3}, Stefan D Anker⁴, Javed Butler⁵, Gerasimos Filippatos⁶, Abhinav Sharma⁷, Francisco Vasques-Nóvoa^{1

3}, Luís Mendonça^{1

8}, João Sérgio Neves^{1

9}, Milton Packer^{10

11}, Faiez Zannad²

Affiliations

¹ RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
² Université de Lorraine, INSERM, Centre d'Investigations Cliniques, CHRU de Nancy, Inserm and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Nancy, France.
³ Serviço de Medicina Interna, Unidade Local de Saúde São João, Porto, Portugal.
⁴ Department of Cardiology (CVK) of German Heart Center Charité, German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany.
⁵ Baylor Scott and White Research Institute, Dallas, TX and University of Mississippi, Jackson, Mississippi, USA.
⁶ National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.
⁷ Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
⁸ Serviço de Nefrologia, Unidade Local de Saúde São João, Porto, Portugal.
⁹ Serviço de Endocrinologia, Unidade Local de Saúde São João, Porto, Portugal.
¹⁰ Baylor University Medical Center, Dallas, Texas, USA.
¹¹ Imperial College, London, UK.

PMID: 41208574
DOI: 10.1111/dom.70289

Abstract

Background: Albuminuria is associated with an increased risk of cardiovascular and kidney events. Sodium glucose co-transporter 2 inhibitors (SGLT2i) reduce albuminuria and improve kidney outcomes in patients with albuminuric chronic kidney disease (CKD). Patients with low- or without albuminuria have been underrepresented in randomised clinical trials (RCTs), and the effects of SGLT2i on cardiovascular and kidney outcomes across the full range of albuminuria require further investigation.

Aims: To study the effects of SGLT2i on kidney and cardiovascular outcomes across albuminuria levels in populations with different cardiovascular-kidney-metabolic (CKM) risk.

Methods: Individual-patient data pooled analysis of RCTs across the CKM spectrum. Outcomes were studied across urinary albumin-to-creatinine ratio (UACR) both as categorical and continuous variables using survival and mixed effects models.

Results: A total of 26 750 patients were included. The median (pct_25-75) baseline UACR was 28 (8-240) mg/g: 13 669 (51.1%) had UACR <30 mg/g, 6904 (25.8%) UACR 30-300 mg/g, and 6177 (23.1%) UACR >300 mg/g. Compared to patients with lower UACR, those with higher UACR were younger, with a more frequent history of hypertension, diabetes, and obesity, and lower eGFR. UACR was linearly associated with kidney and cardiovascular outcomes as well as mortality. Compared to placebo, SGLT2i reduced the risk of kidney events, HF hospitalisations, atherothrombotic events, cardiovascular and all-cause mortality across the full UACR spectrum (Pinteraction >0.1 for all outcomes). Compared to placebo, SGLT2i reduced albuminuria levels by 13%, on average: gMratio 0.87, 95%CI 0.85-0.88, p < 0.001.

Conclusions: Higher albuminuria was associated with an increased risk of cardiovascular and kidney outcomes. SGLT2i improved cardiovascular and kidney outcomes across the full range of albuminuria, including normo-albuminuria.

Keywords: albuminuria; cardiovascular–kidney–metabolic; kidney outcomes; sodium glucose co‐transported 2 inhibitors.

Abstract

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