Wegovy improves heart-related outcomes in obesity regardless of kidney function
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Key takeaways:
- In patients with obesity and heart disease, Wegovy lowered risk for CV events regardless of kidney function.
- The absolute risk difference was greatest in those with poor kidney function.
In patients with obesity and heart disease, semaglutide 2.4 mg reduced risk for major adverse cardiovascular events regardless of baseline kidney function, according to new data from the SELECT trial.
As Healio previously reported, in the main results of SELECT, semaglutide 2.4 mg (Wegovy, Novo Nordisk) reduced risk for major adverse cardiovascular events (MACE), defined as CV death, nonfatal myocardial infarction or nonfatal stroke, by 20% compared with placebo in patients with obesity and preexisting heart disease but without diabetes. During the European Association for the Study of Diabetes meeting, Helen M. Colhoun, MD, FRCP, professor and AXA chair in medical informatics and life course epidemiology at the University of Edinburgh, Scotland, presented a prespecified subanalysis of the treatment effect of semaglutide 2.4 mg based on whether patients had preexisting kidney disease.
In the cohort of 17,604 patients (mean age, 61 years; 84% white; 27% women), 10.9% had impaired kidney function, defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, at baseline, Colhoun said during a presentation.
Results by eGFR
At a median follow-up of 3.5 years, the primary outcome favored the semaglutide group for patients with eGFR less than 60 mL/min/1.73 m2 (9.7% vs. 13.5%; HR = 0.69; 95% CI, 0.52-0.9) and those with eGFR of at least 60 mL/min/1.73 m2 (6% vs. 7.3%; HR = 0.82; 95% CI, 0.72-0.92; P for interaction = .22), Colhoun said.
“There’s clearly a treatment effect, with a separation of the curves, in those with an eGFR above 60, but also in those with an eGFR below 60,” Colhoun said during the presentation. “You can also see the massive effect of eGFR on event rates. The event rate was almost double in those with an eGFR below 60 compared to above.”
In addition, the outcome of MACE plus all-cause mortality — which she said was specified because patients with kidney disease have competing risks for death — also favored the semaglutide group for patients with eGFR less than 60 mL/min/1.73 m2 (12.6% vs. 17.9%; HR = 0.67; 95% CI, 0.53-0.84) and those with eGFR of at least 60 mL/min/1.73 m2 (7.5% vs. 9%; HR = 0.82; 95% CI, 0.74-0.92; P for interaction = .12).
Results by albuminuria
The researchers also stratified the cohort by presence of absence of albuminuria; 11.5% had microalbuminuria, defined as urinary albumin-creatinine ratio (UACR) 30 mg/g to less than 300 mg/g, and 1.9% had macroalbuminuria, defined as UACR 300 mg/g or more. The primary outcome favored the semaglutide group for patients with UACR less than 30 mg/g (5.9% vs. 7.3%; HR = 0.8; 95% CI, 0.7-0.9) and those with UACR of at least 30 mg/g (9.9% vs. 12.3%; HR = 0.8; 95% CI, 0.62-1.02; P for interaction = .97), as did the outcome of MACE plus all-cause death (UACR < 30 mg/g: 7.3% vs. 9.1%; HR = 0.79; 95% CI, 0.71-0.89; UACR 30 mg/g: 12.5% vs. 15.3%; HR = 0.81; 95% CI, 0.65-1.01; P for interaction = .88), Colhoun said.
“Semaglutide is approximately halving the risk difference between people with and without albuminuria in the trial,” Colhoun said during the presentation.
The safety profile of semaglutide 2.4 mg was similar to that of placebo regardless of eGFR or UACR, she said.
“Participants with reduced eGFR and/or albuminuria experienced a much higher rate of MACE, almost twice the rate, in SELECT compared with participants without these risk factors,” Colhoun said during the presentation. “Semaglutide 2.4 mg was at least as effective in relative terms at reducing MACE in participants with and without reduced eGFR and/or albuminuria. Given the increased absolute risk of MACE, what we can see is the absolute risk difference for MACE is greatest in those with reduced kidney function. We did not find any additional safety concerns identified among participants with reduced eGFR and/or albuminuria in SELECT. There was no excess of acute renal failure events.”
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Colhoun HM, et al. OP25. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid.
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