Semaglutide's kidney effects extend to people without diabetes

STOCKHOLM — Improvement in kidney function observed GlucagonGLP-1 receptor agonists in patients Type 2 diabetes Overweight patients and obesity But new research suggests that it's not yet type 2 diabetes.

“These data are important because they are the first to suggest a kidney benefit. Semaglutide “In a patient population without diabetes, this study is effective,” said senior author Helen M. Colhoun, MD, PhD, of the Institute of Genetics and Cancer at the University of Edinburgh in Scotland, UK. Medscape Medical News.

“This group, Chronic kidney disease There is an increased need for kidney protection,” she said.

The latest study was published this week 61st Congress of the European Society of Nephrology (ERA) 2024 and Simultaneous release in Nature Medicine.

SELECT Study in Patients Without Diabetes

The results are from a secondary analysis of a randomized controlled trial. select (Semaglutide heart disease and stroke Overweight patients or obesity) trial evaluated cardiovascular outcomes of semaglutide treatment in 17,604 adults who were overweight or obese but without diabetes and had a history of cardiovascular disease.

The trial's primary endpoint showed that semaglutide reduced major adverse cardiovascular events by 20% compared with placebo.

Obesity is also associated with a significantly increased risk of chronic kidney disease. FLOW TestingKey benefits of semaglutide were also presented at the meeting, showing significant benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes. A secondary analysis of SELECT was conducted to explore whether these kidney benefits extend to people without type 2 diabetes.

Patients were randomized 1:1 to receive semaglutide 2.4 mg subcutaneously once weekly or placebo. Baseline patient characteristics were well balanced, including renal function and albuminuria status.

The primary outcome of the analysis was the time from randomization to the first occurrence of death from renal causes, initiation of chronic renal replacement therapy, or a composite of sustained onset of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m of nephropathy.²a persistent decrease in eGFR of 50% or more compared to baseline; or the development of persistent macroalbuminuria.

After a median follow-up of 182 weeks, results showed that patients in the semaglutide group were significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs. 2.2%, hazard ratio[HR]0.018). [HR]0.78; P = .02).

In the semaglutide group, there was a significant reduction in the decline in eGFR at the pre-specified time point of 104 weeks, with a treatment effect of 0.75 mL/min/1.73m.² (P < .001), and the effect was more pronounced in participants with baseline eGFR < 60 mL/min/1.73 m.² (P < .001).

Furthermore, the increase in urinary uric acid levels was significantly lower in the semaglutide group. albumin-To-Creatinine UACR ratio compared with placebo (–10.7%; P At the prespecified time point of 104 weeks, the treatment effects were -27.2% and -31.4%, respectively, in the randomized groups, with significant improvement (< 0.001) in the UACR 30 to < 300 mg/g group and significant improvement (< 0.001) in the UACR 2300 mg/g group.

The degree of improvement varied by baseline UACR status and was more pronounced in patients with macroalbuminuria: −8.1% in normoalbuminuric patients (n = 14,848), −27% in microalbuminuric patients (n = 1968), and −31% in macroalbuminuric patients (n = 325).

There have been no reports Acute kidney injury associated with semaglutide, regardless of baseline eGFR.

“We were hoping to see a similar effect to what was observed in the diabetes study, but we weren't sure because of the differences in kidney disease between people with type 2 diabetes and those without,” Colhoun said. Medscape Medical News.

Is it a benefit from the weight loss results or something else?

Given the beneficial effect of semaglutide on weight loss, analysis A study published this month also showed an average 10.2% weight loss that lasted for up to four years, but a key question is whether the kidney benefits were a direct result of the weight loss, an effect of the medication, or something else.

But Colhoun said it's still uncertain how weight loss affects kidney benefits, especially considering the range of other factors that may play a role, such as improved cardiometabolism.

“That's a very difficult question to answer,” she said. “We did a mediation analysis that suggested that a large part of the effect could be due to weight change, but weight change also occurred in the placebo group but for different reasons, so that's hard to prove.”

“So while the data suggests there is a weight-related component, we can't attribute it all to weight. [effects] For weight changes.”

Small studies in animals have shown that semaglutide has a direct effect on renal hemodynamics, but they are “small and not conclusive,” Colhoun added.

And while weight loss achieved by other means, such as lifestyle changes, has shown a small effect on eGFR, “interestingly, those studies saw no effect at all on albuminuria, whereas semaglutide had a very large effect on albuminuria,” Colhoun said.

Weight loss research Bariatric surgery Renal benefits have been shown, but these were in type 2 diabetes, unlike the current analysis.

As for whether there will be benefits TirzepatideDual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, which are increasingly used for weight loss, Another secondary analysis It has also shown promising kidney benefits in people with type 2 diabetes, and studies are underway in both type 2 diabetes and obese people without diabetes, Colhoun noted.

Primary prevention of CKD?

A limitation of the current analysis is that only about one-fifth of SELECT participants had an eGFR < 60 mL/min/1.73 m.² or UACR ≥30 mg/g at baseline, suggesting a relatively low proportion of participants with renal disease.

But importantly, the renal benefits seen in patients who are at very high risk for kidney disease but who do not yet have diabetes or CKD are encouraging, said Alberto Ortiz, M.D., Ph.D., chief of nephrology, in a statement commenting on the study. High blood pressure Nephrology Unit, Health Institute of the Jimenez Díaz Foundation, Madrid, Spain.

“It is particularly important that a protective effect was observed in participants with an eGFR greater than 60 mL/min/1.73 m .² “It appears to have reduced the incidence of new-onset CKD across all UACR categories, including those without CKD at baseline,” Ortiz said. Medscape Medical News.

“This suggests a potential role in the primary prevention of CKD in this population,” he said.

To explore this further, he said, “it would be very interesting to evaluate the subgroup outcomes of low-risk KDIGO without CKD to assess whether there is a potential role for primary prevention of CKD in people without CKD at baseline.” [Kidney Disease: Improving Global Outcomes] Categories [of patients]”

SELECT has received funding from Novo Nordisk. Colhoun reports consulting, research, and other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Ortiz reports being a member of the Council of the European Society of Nephrology and the Madrid Society of Nephrology (SOMANE), two societies that developed documents on the treatment of diabetic kidney disease in 2022 with the support of Novo Nordisk. He also reports collaborations with companies developing drugs for kidney disease.