Weekly injections of semaglutide medications like Ozempic significantly reduce the risk of serious kidney outcomes, major cardiovascular events and death among people who have type 2 diabetes and chronic kidney disease, according to a new study.
Diabetes is a key risk factor for kidney disease, which is one of the leading causes of death in the United States and worldwide; about 1 in 3 people with diabetes also has chronic kidney disease, according to the US Centers for Disease Control and Prevention.
But new research shows that weekly injections of semaglutide cut the risk of severe outcomes from diabetic kidney disease by about 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 who were treated with semaglutide, compared with 410 events among those who received the placebo. When scaled by 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 sugar levels in the blood of people with diabetes can damage the blood vessels of the kidneys, and this can also cause strain on the heart. The new study found even broader related benefits of semaglutide treatment among people with diabetic kidney disease.
Kidney function declined more slowly overall, 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 who were treated with semaglutide compared with those who received the placebo, the research found.
The study, published Friday in the New England Journal of Medicine and presented at the European Renal Association Congress, is based on the results of a drug trial conducted among about 3,500 people across 28 countries who were living with both type 2 diabetes and kidney disease. About half of the participants received weekly 1-milligram injections of semaglutide – the dose approved to treat type 2 diabetes under the brand name Ozempic in the US – and the others got a placebo treatment.
Overall, the study participants were followed for an average of about 3½ years. The trial was initially expected to last about four or five years, but findings at the midpoint check-in were so promising that an independent monitoring committee recommended that it end early.
“In this trial, we’re able to show benefits that highlight how transforming semaglutide can be for people with diabetes and kidney disease,” said Dr. Vlado Perkovic, a nephrologist and provost at the the University of New South Wales Sydney. He chairs the trial’s steering committee and was 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 provide benefits for people with diabetic kidney disease, and the researchers note in the new study that “clinicians and patients will need to consider the order and priority of use for semaglutide.”
A combination of therapies could be important, and many of the trial participants were also receiving some other type of treatment 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 only drug manufacturer with semaglutide products that are approved for use in the US – Ozempic for treatment of diabetes and Wegovy for treatment of obesity – and it funded the new study.
Similar benefits were found across all levels of starting kidney function, but there was a particular focus on those at highest risk. More than two-thirds of trial participants were considered to be at very high risk of severe outcomes including kidney failure, cardiovascular events or death, according to risk calculators outlined in global clinical practice guidelines.
In part, focusing on this high-risk group offers clearer insight into the benefits of treatment. But, experts say, many people also don’t realize they have kidney disease until it has reached later stages – and many don’t realize just how dangerous it can be. During each year of this trial, about 8% of the participants had a major kidney event, and almost 5% of people 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 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’s recommended that people with diabetes get tested for kidney disease every six months with blood or urine tests. But this doesn’t always happen, and some people wait until they have symptoms such as fatigue, swelling or changes in urination frequency.
Diabetes treatments are in high demand because it’s such a common disease, said Tuttle, who was also part of the new research. But semaglutide is so promising because it seems to have benefits that apply to multiple complications that can arise because of it. In addition to lowering blood sugar, semaglutide products have been shown to help with weight loss, heart failure and potentially curbing 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, it addresses a broad spectrum of risk,” she said. “It does reduce weight, it does lower glucose in does lower blood pressure a little bit, and then we think on top of that, it has the 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 than White adults, according to CDC data. And Black people in the US are about three times more likely to have kidney failure than White adults.
However, most of the participants in the semaglutide trial were White, and the findings could not be assessed among 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 people who could benefit most from treatment don’t have access to it.
“Now, we have a highly effective therapy that reduces things that really matter to patients, families and communities: keeping their kidney function, preserving life 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.”