CSEM2408 - CSEM General Stream Oral Abstract Presentations - Effect of Semaglutide on Kidney Outcomes in People with Overweight or Obesity and Established Cardiovascular Disease in the SELECT Trial

Blinded Abstract: Background and

Aims:
In the SELECT cardiovascular outcomes trial, semaglutide reduced major adverse cardiovascular events by 20% among people with established cardiovascular disease and overweight or obesity but without diabetes. In this prespecified analysis, main kidney outcomes were examined in SELECT.

Method:
Patients received once-weekly subcutaneous semaglutide 2.4 mg or placebo. The main kidney endpoint was time from randomization to first occurrence of a 5-component nephropathy composite. Blood and urine samples for eGFR and UACR were collected at screening, at 20, 52, 104, 156, 208 weeks of follow-up and at the end of treatment. Analyses were of in-trial data and used Cox regression and mixed models for repeated measures (MMRM).

Results:
In total, 8,803 patients were assigned to semaglutide, 8,801to placebo. Main nephropathy endpoint occurred in fewer of those semaglutide-assigned (1.8%) vs placebo (2.2%): hazard ratio 0.78 [95% CI 0.63, 0.96]; p=0.02 (Fig-1). At 104-weeks, decline in eGFR was less in the semaglutide vs placebo (treatment effect: 0.75 mL/min/1.73 m2 [95% CI 0.43, 1.06]; p< 0.001) (Fig-2A); the proportionate increase in UACR was also less (treatment effect of –10.7% [95% CI –13.2, –8.2]; p< 0.001) (Fig-2B). Semaglutide was not associated with any excess of acute kidney injury regardless of baseline eGFR.


Conclusion:
There was a beneficial effect of once-weekly subcutaneous semaglutide 2.4 mg on a composite kidney endpoint in people with established cardiovascular disease and overweight or obesity but without diabetes. Significant benefits were observed for both eGFR and UACR including lesser eGFR decline in those with baseline eGFR < 60 mL/min/1.73 m2.