Albuminuria-lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo-controlled study
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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.
Original language | English |
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Journal | Diabetes, Obesity and Metabolism |
Volume | 26 |
Issue number | 1 |
Pages (from-to) | 54-64 |
Number of pages | 11 |
ISSN | 1462-8902 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
- diabetic nephropathy, GLP-1 analogue, randomized trial, SGLT2 inhibitor
Research areas
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