SELECT: semaglutide and kidney outcomes in adults without diabetes

Why this study matters

Kidney disease is more common in people living with obesity and heart disease, even without diabetes. The SELECT trial was built to measure heart attacks and strokes, but the researchers planned in advance to look at kidney outcomes too. This paper reports that analysis. It is the first large randomized look at whether semaglutide (Wegovy, Ozempic) affects kidney outcomes in people with a higher body weight and no diabetes, which is why Canadian readers with early kidney concerns may hear about it.

Who was in the study

The analysis used the full SELECT trial: 8,803 people assigned to semaglutide and 8,801 to placebo. Everyone had overweight or obesity and established cardiovascular disease, and no one had diabetes. The main SELECT paper previously reported a 20% reduction in major adverse cardiovascular events. Kidney function (eGFR) was assessed at 104 weeks. The number of weeks of follow-up for kidney events was not extracted.

What the researchers did

SELECT was a randomized, double-blind, placebo-controlled trial. Randomized means chance decided the treatment. Double-blind means neither participants nor staff knew who was on the medicine. Placebo means an inactive injection. People took semaglutide 2.4 mg or placebo by injection once a week.

This paper is a prespecified secondary analysis, meaning the kidney outcomes were written into the plan before the trial began, but they were not the main question the trial was built to answer.

The main kidney outcome combined five events: death from kidney disease, starting long-term kidney replacement therapy (dialysis or transplant), a persistent eGFR below 15, a persistent drop in eGFR of 50% or more, or the onset of persistent macroalbuminuria. eGFR (estimated glomerular filtration rate) is a blood-test estimate of how well the kidneys filter, in millilitres per minute per 1.73 square metres of body surface. Macroalbuminuria means a large amount of protein leaking into the urine.

The analysis counted everyone randomized (intention-to-treat) and used statistical models that compare event rates over time. No adjustment was made for testing several outcomes at once.

What they found

The combined kidney outcome occurred in 1.8% of the semaglutide group and 2.2% of the placebo group (R32-C29). The hazard ratio was 0.78, with a 95% confidence interval of 0.63 to 0.96 and a P value of 0.02. A hazard ratio compares event rates over time; 0.78 means the rate was lower with semaglutide. The confidence interval is the range where the true value most likely sits, and because the whole range is below 1.0, the result is unlikely to be chance.

At 104 weeks, eGFR was 0.75 mL/min/1.73 m² higher with semaglutide than placebo overall (95% CI 0.43 to 1.06; P less than 0.001). In people who started with an eGFR below 60, the difference was 2.19 mL/min/1.73 m² (95% CI 1.00 to 3.38; P less than 0.001).

Side effects and people who stopped

Adverse events led to permanent discontinuation of the study medicine in 16.6% of people on semaglutide and 8.2% on placebo. This paper does not report other side effects; the separate SELECT safety analysis does.

What this study does not tell you

• The combined outcome includes persistent macroalbuminuria, a urine-test finding, alongside more severe events like dialysis. The summary we reviewed does not break the result down by type of event (R32-C30).
• Everyone had established cardiovascular disease and no diabetes. This was not a trial in people with advanced kidney disease.
• It was a secondary analysis with no adjustment for multiple comparisons, so the P values are less firm than for a trial's main outcome.
• The absolute difference was small: 1.8% versus 2.2% over the trial.
• The eGFR difference at 104 weeks is a lab value, and the summary we reviewed does not say how it relates to how people felt or functioned.
• The summary we reviewed does not state the funding source, although SELECT itself was funded by the maker of semaglutide.

What it means in Canada

This analysis suggests a modest kidney benefit in a specific group: adults with heart disease and a higher body weight, without diabetes. It does not show what semaglutide does in people with established kidney disease. For how the medicine is used here, see semaglutide in Canada and public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

Source