Participants with impaired kidney function treated with semaglutide showed a 31% reduction in major adverse cardiovascular events (MACE) and a 33% lower risk of MACE or death from any cause. Reduced eGFR [estimated glomerular filtration rate] and albuminuria are risk factors for MACE, and people with impaired kidney function have increased risk of CVD. The results show that semaglutide is safe and effective in reducing this risk substantially.
SELECT Trial Prespecified Analysis
As previously reported by Medscape Medical News, in the overall SELECT trial results, people with overweight/obesity, CVD, but without diabetes, treated with semaglutide for 3 years or more had a 20% reduced risk of MACE or death due to CVD compared with placebo. Study participants also lost an average 9.4% of their bodyweight.
SELECT enrolled 17,604 adults with a body mass index (BMI) of 27 kg/m² or higher (mean BMI, 33 kg/m²) and a history of CVD across 41 countries. Participants received once-weekly semaglutide (2.4 mg, n = 8803) or placebo (n = 8801). Median follow-up was 3.5 years.
In the total SELECT participant population, 11.1% of participants taking semaglutide had an eGFR < 60 mL/min/1.73 m2 compared with 10.7% taking placebo. The remainder had an eGFR ≥ 60 mL/min/1.73 m2.
Regarding albuminuria, of patients taking semaglutide, 12% had a urinary albumin-to-creatinine ratio (UACR) of 30 to < 300 mg/g, and 11% taking placebo had a UACR of 30 to < 300 mg/g.
MACE (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) comprised the primary endpoint, and the treatment effect on combined MACE and death from any cause was also an endpoint.
Cardiovascular Benefits Maintained
Participants with normal kidney function (≥ eGFR 60 mL/min/1.73 m2) taking semaglutide had an 18% reduction in MACE compared with placebo (6.0% vs 7.3% respectively; HR, 0.82; 95% CI, 0.72 - 0.92). Semaglutide was also linked with an 18% reduction in MACE and death from any cause compared with placebo (7.5% vs 9.0%; HR, 0.82; 95% CI, 0.74 - 0.92) in these patients.
By comparison, in participants with impaired kidney function (eGFR < 60 mL/min/1.73 m2) semaglutide was linked with a 31% reduction in MACE with semaglutide versus placebo (9.7% vs 13.5%; HR, 0.69; 95% CI, 0.52 - 0.90) and a 33% lower risk of MACE and death from any cause (12.6% vs 17.9%; HR, 0.67; 95% CI, 0.53 - 0.84).
The effect on MACE, and on MACE and death from any cause, "was at least as good" in those with reduced eGFR at baseline as those without, said Colhoun. "This is very reassuring that we see at least the same efficacy."
In addition, semaglutide was associated with a 20% reduction in MACE in both those with normal albumin or with albuminuria at baseline, she reported.
Participants with a urinary albumin-to-creatinine ratio (UACR) < 30 mg/g had a MACE event rate of 5.9% with semaglutide and 7.3% with placebo (HR, 0.80; 95% CI, 0.70 - 0.90), while those with a UACR ≥ 30 mg/g had a MACE event rate of 9.9% vs 12.3% (HR, 0.80; 95% CI, 0.62 - 1.02). A similar pattern was found for MACE and death from any cause.
There were no additional safety concerns identified among participants with reduced eGFR and/or albuminuria in SELECT.