Summary: In a phase 2b randomized trial of 248 patients with type 2 diabetes and chronic kidney disease, the dual GLP-1 and glucagon receptor agonist cotadutide produced dose-dependent reductions in urinary albumin-to-creatinine ratio versus placebo at week 14, reaching -43.9% at 300 micrograms and -49.9% at 600 micrograms, with effects sustained to week 26. The endpoint was a surrogate marker of kidney risk rather than a hard renal outcome.
PICO Summary
| Element | Detail |
|---|---|
| Population | 248 adults with type 2 diabetes and CKD (eGFR 20 to under 90 mL/min/1.73 m2; UACR over 50 mg/g); phase 2b multicentre randomized controlled trial across multiple countries. Mean age 67.1 years, 19% female, mean eGFR 55.3 mL/min/1.73 m2, geometric mean UACR 205.5 mg/g; 46.8% on concomitant SGLT2 inhibitors. |
| Intervention | Subcutaneous cotadutide once daily, uptitrated to 100, 300, or 600 micrograms, added to standard of care for 26 weeks (1:1:1:1:1 randomization; roughly 50 patients per arm). |
| Comparison | Daily placebo plus standard of care (double-blind) and semaglutide 1 mg once weekly (open-label), each approximately 50 patients. |
| Outcome | Co-primary endpoints were absolute and percentage change in UACR versus placebo from baseline to week 14. UACR fell dose-dependently, reaching significance at 300 micrograms (-43.9%; 95% CI -54.7 to -30.6) and 600 micrograms (-49.9%; 95% CI -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 micrograms were comparable to semaglutide. No hard renal outcomes (eGFR slope, dialysis, or kidney failure) and no absolute risk reduction or NNT were reported, as this was a surrogate-endpoint trial. |
Cotadutide in Diabetic Kidney Disease
Phase 2b RCT · T2D + CKD · 26 weeks
Cotadutide cut albuminuria dose-dependently versus placebo, roughly halving UACR at 600 micrograms. This is a surrogate endpoint in a small, manufacturer-funded phase 2b trial, so the signal is hypothesis-generating rather than practice-changing.
Expert Commentary
This phase 2b trial offers an encouraging but preliminary signal. Cotadutide lowered albuminuria substantially and dose-dependently on top of contemporary standard of care, and the magnitude at 600 micrograms approached half of baseline UACR, an effect that is biologically plausible for an incretin-based agent and was sustained to week 26. The result should nonetheless be read as hypothesis-generating rather than practice-changing. UACR is a validated surrogate for kidney risk, not a hard outcome, so reductions in albuminuria cannot yet be equated with slowed progression to kidney failure or reduced cardiovascular events. Several caveats temper enthusiasm. The trial was funded by the manufacturer and many authors are company employees, the semaglutide arm was open-label rather than blinded, the sample was modest at roughly 50 patients per arm, and follow-up was short. The authors themselves call for confirmation in a larger study. Can I use this with my patients? Not yet; cotadutide remains investigational and is not approved for diabetic kidney disease, so established agents such as SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists stay first line. A larger, blinded, hard-outcome trial is needed before this agent earns a place in routine nephroprotective care.
References
Selvarajah V, Robertson D, Hansen L, et al. 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 Int. 2024;106(6):1170-1180. doi:10.1016/j.kint.2024.08.023