Summary: In a phase 2b randomized trial of 248 adults with type 2 diabetes and chronic kidney disease, the dual GLP-1 and glucagon receptor agonist cotadutide reduced the urinary albumin-to-creatinine ratio versus placebo at 14 weeks by 43.9% at the 300 microgram dose and 49.9% at the 600 microgram dose, with effects sustained to week 26. The findings represent an early surrogate-endpoint signal rather than proven kidney protection.
PICO Summary
| Element | Detail |
|---|---|
| Population | 248 randomized adults (mean age 67.1 years, 19% female) with type 2 diabetes and chronic kidney disease (eGFR 20 to under 90 mL/min/1.73m2; UACR over 50 mg/g); 46.8% on SGLT2 inhibitors. Multicentre phase 2b randomized controlled trial. |
| Intervention | Subcutaneous cotadutide once daily, uptitrated to 100, 300, or 600 microgram over 26 weeks, plus standard of care (double-blind versus placebo). Five arms randomized 1:1:1:1:1 (approximately 50 per arm). |
| Comparison | Placebo daily plus standard of care (double-blind); and open-label semaglutide 1 mg once weekly as an active reference arm. |
| Outcome | Co-primary endpoint of percentage change in UACR versus placebo to end of week 14: cotadutide 300 microgram -43.9% (95% CI -54.7 to -30.6) and 600 microgram -49.9% (95% CI -59.3 to -38.4); both statistically significant, with effects sustained at week 26. The 100 microgram dose did not reach significance. Serious adverse events were balanced across arms; tolerability of cotadutide 600 microgram was comparable to semaglutide. No hard kidney outcomes (eGFR decline, kidney failure) were tested. |
Cotadutide and albuminuria in diabetic kidney disease
Phase 2b RCT · T2D + CKD · 26 weeks
Cotadutide cut albuminuria 44 to 50% versus placebo on top of standard care, including in SGLT2-inhibitor users. This is a surrogate-endpoint signal, not proven kidney protection, and awaits a larger outcome trial.
Expert Commentary
This phase 2b trial provides an encouraging but preliminary signal: cotadutide produced dose-dependent, statistically significant reductions in albuminuria on top of standard care, including in patients already taking SGLT2 inhibitors. The verdict, however, must be measured. The co-primary endpoint was UACR, a validated surrogate that tracks with kidney risk but is not itself a hard outcome, so reduced albuminuria cannot yet be equated with slowed progression to kidney failure or a delay in eGFR decline. The most important limitation is design and duration: the study was a 26-week dose-finding trial powered for a surrogate, and the authors themselves state that the kidney-protective benefit needs confirmation in a larger study. Additional caution is warranted because the trial was funded by the manufacturer, the semaglutide comparator arm was open-label rather than blinded, and albuminuria is responsive to short-term haemodynamic and glycaemic effects that may not translate into durable structural benefit. Can I use this with my patients? Not yet. Cotadutide remains investigational and has no kidney indication, so it should not replace established renoprotective therapy such as SGLT2 inhibitors, ACE inhibitors or ARBs, and finerenone where indicated. The signal justifies the planned larger outcome trial, and that is where its real value should be judged.
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