A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m<sup>2</sup> and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m<sup>2</sup>, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

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Publication Details

Journal
Kidney International
Published
2024-08-31
DOI
https://doi.org/10.1016/j.kint.2024.08.023
Citations
28
Primary Topic
Diabetes Treatment and Management
Type
article
Field-Weighted Citation Impact
10.02

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article

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease

Carl A. Peters, John Baker, Viknesh Selvarajah, José Sánchez et al.
28 citations
Kidney International
Diabetes Treatment and Management
10.02
article

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease

Carl A. Peters, John Baker, Viknesh Selvarajah, José Sánchez, R Dumas, Albert Lecube, Hiddo J.L. Heerspink, Yi‐Ting Chang, Lutz Jermutus, Cristóbal Morales, Darren Robertson, Karl-Michael Derwahl, Ronald Goldenberg, Hongtao Yu, Angela Coggi, Sonja Y. Hess, Anis A. Khan, Russell Scott, Joanna Parkinson, Victoria E R Parker, Lars Hansen, Kirsten Smith, Tom G. Elliott, Tabbatha Duck, Simran Jolly, H. Sophia Chung
article en
28 citations

Abstract

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m<sup>2</sup> and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m<sup>2</sup>, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

Kidney InternationalVol. 106(6)
AstraZeneca (United Kingdom) (GB), University Medical Center Groningen (NL), Universitat de Lleida (ES), University of Groningen (NL), Middlemore Hospital (NZ), Hospital Universitari Arnau de Vilanova (ES), Hospital Universitario Virgen Macarena (ES), Waitemata District Health Board (NZ), Bioinformatics Solutions (Canada) (CA), AstraZeneca (Australia) (AU), The George Institute for Global Health (AU), Spanish Clinical Research Network (ES), AstraZeneca (France) (FR), LMC Diabetes & Endocrinology (Canada) (CA), AstraZeneca (Netherlands) (NL), Institute of Clinical Cancer Research (DE), Christchurch Clinical Studies Trust (NZ), AstraZeneca (Japan) (JP), Instituto de Investigación Biomédica de Lleida (ES), AstraZeneca (Poland) (PL), Centre hospitalier de l'Université Laval (CA), AstraZeneca (Sweden) (SE), Centre Intégré de Santé et de Services Sociaux des Laurentides (CA), Centre intégré de santé et de services sociaux de Chaudière-Appalaches (CA), AstraZeneca (United States) (US), Université Laval (CA), McMaster University (CA)
Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Alexion Pharmaceuticals, CSL Behring, Novo Nordisk, Vifor Pharma
Good health and well-being
Openalex Percentile: Top 1%
Diabetes Treatment and Management
10.02
DOIOpen Access PDFOpenAlex
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