Semaglutide Reduces MACE, Death in Impaired Kidney Function

MADRID, Spain — Semaglutide (Wegovy) prevents major cardiac events including death in adults with overweight/obesity and cardiovascular disease (CVD), both with and without impaired kidney function, a subgroup analysis of the Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial shows. 

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. 

“These findings have important clinical implications,” said Helen Colhoun, PhD, specialist in medical informatics at the University of Edinburgh, UK, who presented the results at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

“We know 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,” she told attendees. 

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.

“We looked at this [death from any cause] because there’s always a competing risk of death from other causes in this population with reduced kidney function,” explained Colhoun. 

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. 

Commenting on the work, comoderator, Fiona Gribble, MBChB, DPhil, professor of endocrine physiology, University of Cambridge, UK, said: “I think the results showed very convincingly that semaglutide works very effectively in people with impaired kidney function as without.”

“It’s pleasing to see that there aren’t subpopulations that need to be excluded,” she said. “This is a patient group that will benefit.”

The other moderator, Jens Holst, MD, DMSc, professor of medical physiology and deputy head of the department of biomedical sciences, University of Copenhagen, Denmark, also commented on the work. “It was a fine presentation. If there had been more time, I would have asked her if there was anything that went against their expectations at all. I don’t think there was.”

However, he added that the apparent increased effect size in people with impaired kidney function was more difficult to appreciate. “It is a little bit like the effects on A1c: the higher the baseline value, the greater the drop. What really matters is the actual improvement in CVD risk compared to people without [impairment]. If it is only relatively better, it is perhaps not so important.” 

But, Holst added, the data are encouraging. “Many people these days talk about the link between kidney function and CVD, and this study supports that improving one also improves the other.”

Colhoun has reported serving on advisory panels for Novo Nordisk and Bayer; receiving research funding from Sanofi, Roche, and IQVIA, and grants from the Chief Scientist Office, Diabetes UK, European Commission, JDRF, and Medical Research Council; serving on a speaker‘s bureau for Novo Nordisk; and holding stock in Roche Pharmaceuticals and Bayer. Gribble has declared no financial relationships. Holst has declared participating in advisory boards for Novo Nordisk and being a founder and board member of Antag.