Summary: In a phase 2b trial of 248 patients with type 2 diabetes and chronic kidney disease, the GLP-1 and glucagon receptor agonist cotadutide produced dose-dependent reductions in urinary albumin-to-creatinine ratio versus placebo at week 14, reaching significance at 300 micrograms (-43.9%) and 600 micrograms (-49.9%), with effects sustained at week 26. The 100 microgram dose was not significant, and the outcome was a surrogate marker of albuminuria rather than a hard kidney endpoint.
PICO Summary
| Element | Detail |
|---|---|
| Population | 248 patients with type 2 diabetes and chronic kidney disease (eGFR 20 to under 90 mL/min/1.73 m2, UACR over 50 mg/g); phase 2b, multicentre, randomised; 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 SGLT2 inhibitors. |
| Intervention | Subcutaneous cotadutide uptitrated to 100, 300, or 600 micrograms daily for 26 weeks, added to standard of care; randomised 1:1:1:1:1 (approximately 50 patients per arm). |
| Comparison | Placebo once daily (double-blind, approximately 50 patients) or semaglutide 1 mg once weekly (open-label, approximately 50 patients), both with standard of care. |
| Outcome | Co-primary endpoint of percentage change in UACR versus placebo, baseline to week 14: significant at 300 micrograms (-43.9%, 95% CI -54.7 to -30.6) and 600 micrograms (-49.9%, 95% CI -59.3 to -38.4); 100 micrograms not significant. Effects sustained at week 26. Serious adverse events balanced across arms; 600 micrograms tolerability comparable to semaglutide. No hard kidney outcomes (eGFR decline, kidney failure) reported; ARR/NNT not applicable to this surrogate endpoint. |
Cotadutide in diabetic kidney disease
Phase 2b RCT · T2D + CKD · 26 weeks
Cotadutide cut albuminuria by 44 to 50 percent at the higher doses on top of standard of care, but UACR is a surrogate and a 26-week study cannot prove kidney protection. Hypothesis-generating, awaiting a powered outcomes trial.
Expert Commentary
This phase 2b trial is best read as hypothesis-generating rather than practice-changing. A dose-dependent fall in albuminuria of roughly 44 to 50 percent at the higher doses is biologically encouraging, and the confidence intervals are tight enough to be taken seriously, but the primary outcome is a surrogate. UACR reduction has predicted long-term kidney protection for several drug classes, yet it is not itself a hard endpoint, and a 26-week study cannot demonstrate preservation of eGFR or prevention of kidney failure. The honest verdict is that cotadutide lowers albuminuria on top of standard of care, including in patients already taking SGLT2 inhibitors, and that this signal warrants a properly powered outcomes trial. The most relevant limitation is design: the semaglutide comparison was open-label, so the apparent similarity in tolerability between cotadutide 600 micrograms and semaglutide should be treated cautiously, and the trial was sponsored by the manufacturer of cotadutide, which reinforces the need for independent confirmation. Can I use this with my patients? Not yet. There is no licensed indication and no hard-outcome evidence, so this does not change management for a person with diabetic kidney disease today. What it should do is prompt clinicians to optimise the proven foundations, RAS blockade, SGLT2 inhibition, and finerenone where indicated, while awaiting the larger study the authors themselves call for.
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