Semaglutide’s cardiovascular benefits are maintained in people with impaired kidney function

The anti-obesity medication semaglutide may help to prevent heart attacks, strokes, and other major adverse cardiovascular events (MACE) as well as death in adults with overweight or obesity who don’t have diabetes, whether or not they also have impaired kidney function, according to new research to be presented at this year’s Annual Meeting of The European Association for the Study of Diabetes (EASD), Madrid (9-13 Sept).

The results are based on a pre-specified analysis of the SELECT trial which found that adults with overweight or obesity but not diabetes taking semaglutide for more than 3 years had a 20% lower risk of MACE or death due to cardiovascular disease, and lost an average 9.4% of their bodyweight [1]. 

“This new analysis found a similar percentage reduction in cardiovascular disease with semaglutide in those with and without poor kidney function in SELECT. Because those with poor kidney function have higher background risk of cardiovascular disease the absolute benefit is greatest in this group,” explained lead author Professor Helen Colhoun from the University of Edinburgh, UK.

She added: “These findings have important clinical implications. People with impaired kidney function have increased risks of cardiovascular disease and the results show that semaglutide is safe and effective in reducing this risk substantially.”

Obesity is strongly associated with diabetes and chronic kidney disease, and is known to exacerbate the risk of kidney function decline and macroalbuminuira (abnormal amounts of the albumin protein in urine).

Semaglutide is a GLP-1 medication primarily prescribed for adults with type 2 diabetes but at the 2.4mg dose is approved for weight loss in people with obesity or overweight who have at least one other health issue. This class of medications simulate the functions of the body’s natural incretin hormones, which help to lower blood sugar levels after a meal. Adjusting these hormone levels can also make people feel full, and in doing so, helps lower their daily calorie intake.

Between October 2018 and June 2023, 17,604 adults (aged 45 or older; 72% male) from 804 sites in 41 countries with overweight or obesity (BMI of 27 kg/m² or higher) were enrolled in the SELECT trial and treated with semaglutide (2.4mg) or placebo for an average of 40 months.

They had previously experienced a heart attack, stroke and/or had peripheral artery disease, but did not have type 1 or type 2 diabetes when they joined the study.
The new analysis examined whether semaglutide’s effect on MACE and a combined endpoint of MACE or death from any cause is maintained in participants with impaired kidney function, defined as low filtration rates and high levels of protein in the urine. This was measured according to estimated glomerular filtration rate (eGFR; a measure of kidney function in removing waste and excess water from the blood through urine) and albuminuria status at randomisation.

At randomisation, 1,908 (11%) participants had eGFR <60 mL/min/1.73 m² and 2,281 (13%) had urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g (indicating impaired kidney function).

Over a median follow-up of 3.5 years, semaglutide was linked to an 18% reduction in MACE (6% in the semaglutide group had such events vs. 7.3% in the placebo group), as well as an 18% reduction in MACE or death from any cause in adults with normal kidney function (eGFR ≥60).

In participants with impaired kidney function (eGFR <60) semaglutide was linked to a 31% reduction in MACE (9.7% semaglutide vs. 13.5% placebo), and a 33% lower risk of MACE or death from any cause.

The researchers also found that in participants with normal levels of AUCR (<30), semaglutide was linked to a 20% reduction in MACE (5.9% semaglutide vs. 7.3% placebo), as well as a 21% reduced risk of MACE or all-cause mortality.

Similarly, in participants with higher levels of UACR (≥30), indicating kidney damage or disease, semaglutide was linked to a 20% reduction in MACE compared with placebo (9.9% vs 12.3%) and a 19% lower risk of MACE or death from any cause.

Among those with impaired kidney function (eGFR <60) serious adverse events were reported in 37% of those allocated to semaglutide compared to 46% of those on placebo.

“The SELECT trial showed the benefits of semaglutide for adults with cardiovascular disease who were living with obesity or overweight but didn’t have diabetes. This new analysis finds that within this group, people with impaired kidney function had much higher rates of cardiovascular disease,” said Professor Colhoun.

“However, semaglutide was at least as effective at preventing heart attacks and other major cardiac events as well as deaths in this group as it was in those with normal kidney function. The findings add to the growing evidence of the cardiovascular benefits of semaglutide  and underscore its important role as a treatment option in the management of cardiovascular and renal health for the growing number of people affected by obesity.”

Despite the important findings, the authors caution that SELECT was not a primary prevention trial, so the results cannot be extrapolated to patients with kidney failure in general.