Weekly injections of semaglutide medications like Ozempic significantly lower the risk of severe kidney outcomes, major cardiovascular events, and death among individuals with type 2 diabetes and chronic kidney disease, according to a new study.
Diabetes is a major risk factor for kidney disease, which is one of the leading causes of death in the United States and globally; about one in three people with diabetes also has chronic kidney disease, according to the US Centers for Disease Control and Prevention.
New research demonstrates that weekly injections of semaglutide reduce the risk of severe outcomes from diabetic kidney disease by approximately 24%.
These severe outcomes – including significant loss of kidney function, kidney failure, and death from kidney or cardiovascular causes – occurred 331 times among trial participants treated with semaglutide, compared to 410 events among those who received a placebo.
When adjusted for the number of years each person was in the trial, there were 5.8 events for every 100 years of follow-up among those taking semaglutide, compared with 7.5 events for every 100 years of follow-up among those who received the placebo.
High blood sugar levels in individuals with diabetes can damage the blood vessels of the kidneys, which can also strain the heart. The new study found even broader benefits of semaglutide treatment among people with diabetic kidney disease.
Kidney function declined more slowly, the risk of major cardiovascular events such as heart attack was 18% lower, and the risk of death from any cause was 20% lower among people treated with semaglutide compared to those receiving the placebo.
The study, published Friday in the New England Journal of Medicine and presented at the European Renal Association Congress, is based on results from a drug trial involving about 3,500 people across 28 countries who had both type 2 diabetes and kidney disease.
Approximately half of the participants received weekly 1-milligram injections of semaglutide – the dose approved for treating type 2 diabetes under the brand name Ozempic in the US – while the others received a placebo treatment.
Participants were followed for an average of about 3½ years. The trial, initially expected to last four to five years, concluded early due to promising findings at the midpoint check-in, as recommended by an independent monitoring committee.
“In this trial, we’re able to show benefits that highlight how transformative semaglutide can be for people with diabetes and kidney disease,” said Dr. Vlado Perkovic, a nephrologist and provost at the University of New South Wales Sydney. He chairs the trial’s steering committee and was the lead author of the new study.
“The effect size was a bit larger than we had expected, and therefore, the results were highly statistically significant. So the likelihood of this being a chance finding is infinitesimally small, and I think we can be highly confident that the results are robust and real.”
Three other drug treatments have been shown to benefit people with diabetic kidney disease, and the researchers note in the study that “clinicians and patients will need to consider the order and priority of use for semaglutide.”
A combination of therapies could be crucial, as many trial participants were also receiving other treatments for their diabetes.
“Semaglutide showed some benefits on top of what is currently considered standard of care,” said Martin Holst Lange, executive vice president of development for Novo Nordisk.
The Danish company is the sole manufacturer of semaglutide products approved for use in the US – Ozempic for diabetes treatment and Wegovy for obesity treatment – and funded the new study.
Similar benefits were observed across all levels of starting kidney function, with a particular focus on those at highest risk. More than two-thirds of trial participants were deemed at very high risk for severe outcomes, including kidney failure, cardiovascular events, or death, according to risk calculators in global clinical practice guidelines.
Focusing on this high-risk group provides clearer insight into the benefits of treatment. However, many people do not realize they have kidney disease until it has progressed to later stages, and many are unaware of its dangers.
Throughout the trial, about 8% of participants experienced a major kidney event, and nearly 5% died.
“Kidney disease attributed to diabetes, or diabetic kidney disease, is one of the most common and deadly complications of diabetes.
Yet, unfortunately, there’s very low awareness around it,” said Dr. Katherine Tuttle, chair of the Diabetic Kidney Disease Collaborative for the American Society of Nephrology.
She is also the executive director for research at Providence Inland Northwest Health, an investigator with the Institute of Translational Health Sciences, and a professor of medicine at the University of Washington.
“Part of the problem is that the condition is asymptomatic until late stages, so physicians and patients have to be very intentional about identifying kidney disease.”
It is recommended that individuals with diabetes be tested for kidney disease every six months with blood or urine tests, but this does not always occur.
Some people only seek medical attention when symptoms such as fatigue, swelling, or changes in urination frequency appear.
Diabetes treatments are in high demand due to the prevalence of the disease, said Tuttle, who also contributed to the new research.
Semaglutide is particularly promising because it seems to offer benefits across multiple complications associated with diabetes.
In addition to lowering blood sugar, semaglutide products have been shown to aid in weight loss, improve heart failure, and potentially curb addictive behaviors.
“I think these drugs that affect multiple final common pathways are really highly effective because when we try to just treat one risk factor, it’s almost like putting your finger in the dike.
You can’t plug all the holes. To me, what semaglutide really does is address a broad spectrum of risk,” she said. “It does reduce weight, it does lower glucose, it does lower blood pressure a little bit, and then we think on top of that, it has direct effects on the kidney. It’s really the whole package.”
There are significant disparities in diabetes prevalence and kidney disease in the US. Black, Hispanic, and American Indian adults are nearly twice as likely to have diabetes compared to White adults, according to CDC data.
Additionally, Black people in the US are about three times more likely to experience kidney failure than White adults.
However, most participants in the semaglutide trial were White, and the findings could not be assessed among these important subgroups.
“When we have something that’s effective, we also have to turn our sights to getting treatments to patients,” Tuttle said. But many of the highest-risk individuals who could benefit most from treatment do not have access to it.
“Now, we have a highly effective therapy that reduces things that really matter to patients, families, and communities: preserving kidney function, saving lives, and reducing the rates of cardiovascular events.
But that’s all great only if people get the treatment,” she said. “So now, really, the challenge before all of us is to move much more expeditiously from evidence generation to implementation.”
