Cotadutide, a dual GLP-1/glucagon receptor agonist, dose-dependently reduced urine albumin by up to 50% in 248 patients with diabetic kidney disease, with safety comparable to semaglutide.
-49.9% UACRCotadutide 600 μg reduced the kidney damage marker UACR by nearly 50% in diabetic kidney disease patients, on top of standard care including SGLT2 inhibitors
What the researchers found
Cotadutide dose-dependently reduced UACR at week 14: 300 μg (-43.9%, CI -54.7 to -30.6) and 600 μg (-49.9%, CI -59.3 to -38.4) vs placebo. Effects sustained at 26 weeks. Safety of cotadutide 600 μg comparable to semaglutide. Serious AEs balanced across arms. 46.8% on concomitant SGLT2i.
Why it matters
Diabetic kidney disease is the leading cause of kidney failure worldwide. While GLP-1 agonists and SGLT2 inhibitors offer some kidney protection, cotadutide's dual mechanism (adding glucagon receptor activation) produced nearly 50% albuminuria reduction — potentially a more powerful kidney-protective approach for high-risk patients.
The numbers in context
Patients with eGFR 20-90 mL/min/1.73m² and UACR >50 mg/g. 26-week treatment. 1:1:1:1:1 randomization.
How the study worked
Phase 2b, randomized, double-blind (cotadutide vs placebo), open-label (semaglutide) trial. 248 patients with T2D and CKD (eGFR 20-90, UACR >50 mg/g) randomized 1:1:1:1:1 to cotadutide 100, 300, or 600 μg daily, placebo daily, or semaglutide 1 mg weekly for 26 weeks. Co-primary endpoints: absolute and percentage UACR change from baseline to week 14.
Who was studied
T2D patients with CKD (eGFR 20-90, UACR >50 mg/g)
What this study cannot tell us
Phase 2b — not powered for hard kidney endpoints (progression to dialysis, eGFR decline). UACR is a surrogate marker. Open-label semaglutide arm may introduce bias. 26-week duration may not reflect long-term kidney protection. Cotadutide requires daily injection vs semaglutide's weekly dosing.
How to read the evidence
Rated moderate: well-designed phase 2b RCT with adequate sample size for signal detection, but UACR is a surrogate endpoint and the study wasn't powered for hard kidney outcomes.
When this study was published
Published in 2024 in Kidney International. Provides key data for designing phase 3 trials of cotadutide in diabetic kidney disease.
The bigger picture
This adds cotadutide to the growing list of peptide-based drugs showing kidney protection in diabetes. The near-50% UACR reduction on top of standard care (including SGLT2i in nearly half) suggests additive kidney protection from targeting multiple metabolic pathways simultaneously.
Questions still open
- Will cotadutide's UACR reduction translate to fewer patients progressing to kidney failure in larger, longer trials?
- How does cotadutide compare head-to-head with semaglutide for kidney protection?
- Would combining cotadutide with SGLT2i provide even greater kidney protection than either alone?
Common questions
Can peptide drugs protect the kidneys in diabetes?
What is cotadutide and how is it different from semaglutide?
Read the original research
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.
Kidney international, 106(6), 1170-1180
Citation
Selvarajah, Viknesh; Robertson, Darren; Hansen, Lars; Jermutus, Lutz; Smith, Kirsten; Coggi, Angela; Sánchez, José; Chang, Yi-Ting; Yu, Hongtao; Parkinson, Joanna; Khan, Anis; Chung, H Sophia; Hess, Sonja; Dumas, Richard; Duck, Tabbatha; Jolly, Simran; Elliott, Tom G; Baker, John; Lecube, Albert; Derwahl, Karl-Michael; Scott, Russell; Morales, Cristobal; Peters, Carl; Goldenberg, Ronald; Parker, Victoria E R; Heerspink, Hiddo J L. (2024). 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.. Kidney international, 106(6), 1170-1180. https://doi.org/10.1016/j.kint.2024.08.023