Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial

Global Kidney Trials Insights: A guide for Everyone

Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial

Global Kidney Trials Insights: A Guide for Everyone

1. The Question for Investigation

Chronic kidney disease (CKD) is a progressive condition that often leads to kidney failure, and it is incredibly challenging in people with obesity, due to the added strain on kidney function.

The SMART trial set out to explore whether semaglutide (Ozempic), a medication commonly used to manage obesity and diabetes (including individuals with diabetes and CKD), could protect the kidneys and address other health challenges related to obesity in patients with CKD who do not have diabetes. This study focused on the drug’s impact on reducing urine albumin-to-creatinine ratio (UACR), an essential marker of kidney damage. It also examined other potential benefits, such as weight loss and reduced inflammation.

2. The findings of the study

The trial involved 101 participants aged 18 to 75 with CKD (but without diabetes), a body mass index (BMI) of 27 kg/m² or higher, and varying degrees of kidney function. Over 24 weeks, participants received either semaglutide 2.4mg per week or a placebo, with the primary outcome being changes in UACR. The findings revealed significant benefits:

  1. Reduction in Kidney Damage Markers: Compared to the placebo group, participants receiving semaglutide showed a 52% reduction in UACR. This suggests less kidney stress and potentially slower progression of CKD.
  2. Weight Loss: Those treated with semaglutide experienced substantial weight reductions, averaging 9.1 kg. This is especially valuable in CKD patients, as obesity worsens kidney disease progression.
  3. Additional Benefits: The drug also reduced waist circumference and potentially lowered kidney inflammation, although further studies are needed to confirm these effects.

Changes in kidney filtration rates (eGFR) between the two groups were minimal. However, early declines in eGFR in the semaglutide group might reflect temporary changes rather than long-term harm.

While the trial was relatively short, it highlighted semaglutide’s promise in reducing kidney damage markers and addressing obesity in non-diabetic CKD patients. Researchers emphasized the need for more extensive and longer-term studies to evaluate its effects on preventing dialysis or kidney failure. Overall, the SMART trial positions semaglutide as a potential game-changer for managing CKD in obese patients, especially those without diabetes, marking a significant step forward in nephrology and weight management research.

This edition was edited by Megan Borkum, ISN-ACT Global Trials Focus Coordinator, and Richard Knight, member of the Patient Liaison Advisory Group.

Glossaries

Read the GTF editorial team’s review of the SMART trial here.
Access the complete study here.
Any questions? Contact us at research@theisn.org

Glossaries

Adrenal glands are small glands that sit on top of the kidneys.

Efficacy refers to how well a medication or treatment works in achieving its intended effect.

Aldosterone is a hormone produced by your adrenal glands, which sit on top of your kidneys. It's kind of like a chemical messenger that helps regulate the amount of water and salt in your body.

Semaglutide is a medication used to treat type 2 diabetes and help with weight loss. It works by mimicking a hormone (called GLP-1) in the body that helps control blood sugar and appetite. It's usually given as an injection.

Random assignment (or randomisation) is a way of putting people into different groups in a study by chance, like flipping a coin. This helps make sure the groups are similar at the start of the study, so researchers can better tell if a treatment is really working.

Cardiovascular disease refers to diseases that affect the heart and blood vessels. This includes problems like heart attacks, strokes, and heart failure. Diabetes, high cholesterol, high blood pressure, and being overweight can damage the blood vessels and cause cardiovascular disease.

refers to the best way to take care of patients

refers to an event over time that is measured to monitor the impact of a treatment in a given population.

Delayed graft function happens when a transplanted kidney does not start working right away and needs additional support with dialysis to help remove excess fluid and waste from the blood, Delayed graft function can be linked to several problems, including the need for ongoing dialysis until the kidney works well enough, longer hospital stays, a higher risk of kidney failure, and death.

This contains the electrolytes commonly found in our bodies. It has extra minerals like potassium and magnesium that are important to help keep our bodies healthy.

It contains primarily salty water. It is commonly used during and early after the transplant surgery; and

Arteriovenous fistula (AVF): irregular connection between an artery and a vein

Hemodiafiltration, is combining this process with direct fluid removal by adding many tiny holes, also called pores, to the membrane. These pores allow fluid and waste to be passed through more easily, including larger wastes that might not otherwise be removed through dialysis. As this process involves much more fluid being removed, some replacement waste-free fluid is added to the filtered blood before it returns to the body. It is unclear if this approach improves heart health and survival. 

In hemodialysis, wastes are removed from the blood by travelling through a barrier (called a membrane) in the filter of the dialysis machine, which allows wastes to pass through but aims to keep important parts of the blood, like blood cells and protein, in the bloodstream. One challenge of this approach is that some larger wastes (called middle-molecular-weight molecules), do not pass through the barrier very well. The build-up of these wastes may increase the risk of health problems, including for heart health.