FLOW vs AWARD-7 vs LEADER Renal Substudy: GLP-1 Receptor Agonists and Kidney Outcomes Compared

What did FLOW test?

FLOW randomized adults with type 2 diabetes and chronic kidney disease to subcutaneous semaglutide 1.0 mg weekly or placebo [1]. Entry required albuminuria on one of two strata: eGFR 50 to 75 mL/min/1.73 m² with a urine albumin-to-creatinine ratio above 300 and below 5,000 mg/g, or eGFR 25 to below 50 mL/min/1.73 m² with a ratio above 100 and below 5,000 mg/g [1]. The primary outcome was a composite of kidney failure (dialysis, transplant, or eGFR under 15 mL/min/1.73 m²), at least a 50% reduction in eGFR from baseline, or death from kidney-related or cardiovascular causes [1].

How large was the kidney benefit?

Median follow-up was 3.4 years, with 1,767 people on semaglutide and 1,766 on placebo [1]. The primary outcome occurred as a first event in 331 people on semaglutide and 410 on placebo, a 24% lower risk (HR 0.76, 95% CI 0.66 to 0.88; P=0.0003) [1]. The kidney-only components moved the same way (HR 0.79, 95% CI 0.66 to 0.94), and the mean annual eGFR slope was less steep by 1.16 mL/min/1.73 m² per year (P<0.001) [1].

Death from any cause was a confirmatory secondary outcome and was 20% lower with semaglutide (HR 0.80, 95% CI 0.67 to 0.95; P=0.01) [1]. Cardiovascular death was also lower, with an HR of 0.71 (95% CI 0.56 to 0.89) [1]. Early trial cessation was recommended at a prespecified interim analysis [1].

Why the three drugs cannot be ranked

FLOW's 24% belongs to a composite that includes cardiovascular death, in adults with diabetes and albuminuric CKD, against placebo [1]. Semaglutide and dulaglutide were compared head to head in SUSTAIN 7, but that trial's primary endpoint was the change in HbA1c, not a kidney outcome [4]. We found no kidney-outcome results for dulaglutide or liraglutide to set beside FLOW.

What the labels say

Ozempic, the semaglutide product labeled for type 2 diabetes, carries an indication for kidney outcomes in type 2 diabetes with chronic kidney disease [2]. Wegovy is the weight-management semaglutide product, labeled for weight reduction, cardiovascular risk reduction and MASH [3].

The Wegovy label warns about acute kidney injury due to volume depletion and calls for renal-function monitoring when adverse reactions could cause volume depletion [3].