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

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: ) baseline UACR was 28 (8-240) mg/g: 13 669 (51.1%) had 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.