Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min−1 1.73 m−2 and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g−1) and body mass index ≥27 kg m−2. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g−1 (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min−1 1.73 m−2; and mean body mass index was 36.2 (s.d. 5.6) kg m−2. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by −52.1% (95% confidence interval −65.5, −33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 . In participants with obesity and chronic kidney disease without diabetes, once-weekly administration of semaglutide 2.4 mg led to a reduction in albuminuria, body weight and systolic blood pressure compared with placebo, with no changes to creatinine or cystatin-C estimated glomerular filtration rate or measured glomerular filtration rate during the 24-week follow-up period.