Albuminuria‐lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo‐controlled study

Abstract Aim To investigate whether combined treatment with empagliflozin (a sodium‐glucose cotransporter‐2 inhibitor) and semaglutide (a glucagon‐like peptide‐1 receptor agonist) can reduce urinary albumin‐creatinine ratio (UACR) compared to treatment with empagliflozin alone in individuals with type 2 diabetes (T2D) and albuminuria. Methods We conducted a randomized, placebo‐controlled, double‐blind, parallel study including 60 individuals with T2D and albuminuria. All participants initiated open‐label empagliflozin 25 mg once daily, on top of renin‐angiotensin system inhibition, in a run‐in period of 26 weeks. Subsequently, participants were randomized to semaglutide or placebo 1 mg once weekly for 26 weeks. The primary endpoint was change in UACR. Secondary endpoints were change in: (i) measured glomerular filtration rate (GFR); (ii) 24‐hour systolic blood pressure; (iii) glycated haemoglobin (HbA1c) level; (iv) body weight; and (v) plasma renin and aldosterone levels. Results Addition of semaglutide to empagliflozin provided no additional change in UACR from randomization to end‐of‐treatment. The mean (95% confidence interval) difference in UACR was –22 (–44; 10)% ( P = 0.15) between treatment groups. Neither GFR, 24‐hour blood pressure, body weight, nor plasma renin activity was changed with semaglutide. HbA1c (–8 [–13; –3] mmol/mol; P = 0.003) and plasma aldosterone (–30 [–50; –3] pmol/L; P = 0.035) were reduced with semaglutide compared to placebo. Conclusions Semaglutide added to empagliflozin did not change UACR, measured GFR, 24‐hour systolic blood pressure, body weight or plasma renin levels in individuals with T2D and albuminuria. Semaglutide improved glycaemic control and plasma aldosterone levels compared to placebo.