The blockbuster diabetes drug Ozempic — also sold as the obesity drug Wegovy — can add another health condition to the list of maladies it alleviates. Researchers presented clinical-trial data today at a conference in Stockholm, showing that it significantly reduces the risk of kidney failure and death for people with type 2 diabetes and chronic kidney disease. Scientists are thrilled with the result, and think that the drug, otherwise known by its generic name, semaglutide, will eventually be proved to help a more general population of people with kidney disease. This trial is a first step towards that goal, they say.
Semaglutide manufacturer Novo Nordisk, based in Bagsværd, Denmark, announced in October that it had halted its kidney-disease trial because of a recommendation from an independent data-safety monitoring board that the overwhelmingly positive results made it unethical to continue to give some participants a placebo. But until now, it hadn’t revealed the full data analysis, which is also published today in The New England Journal of Medicine1.
Broad benefits
The phase IIIb trial, which enrolled 3,533 people, showed that those who received semaglutide injections weekly were 24% less likely to have ‘major kidney disease events’, including kidney failure and dying owing to kidney complications, than were those getting a placebo. Kidney failure occurs when one or both of the kidneys no longer functions on its own, and can be treated with dialysis or a kidney transplant.
Participants who received semaglutide were also 29% less likely to die from heart attacks and other major cardiovascular incidents than were those who got a placebo, and 20% less likely to die from any cause during the trial period. This is huge because “the links between kidney disease and heart disease are really profound”, says Samir Parikh, a nephrologist at the University of Texas Southwestern Medical Center in Dallas who was not involved in the study.
People with type 2 diabetes and chronic kidney disease often die of heart disease before their kidney problems progress to failure. Heart disease and chronic kidney disease are strongly linked, Parikh says, and “unfortunately, they are self-reinforcing”. Adding in type 2 diabetes is like throwing “rocket fuel” onto the fire, he adds. This is because type 2 diabetes can damage small blood vessels in the body, including those in the heart and kidneys.
“We are ecstatic that we are seeing real benefits” for people with chronic kidney disease, says Katherine Tuttle, a nephrologist at the University of Washington School of Medicine in Spokane who co-ran the trial. “These patients benefit broadly.”
Need for therapies
Globally, the death rate from heart disease dropped by about 30% between 1990 and 2019, owing to improvements in health care and people changing their behaviour — for instance, stopping smoking. But people with chronic kidney disease have not seen the same drop in heart-related deaths. “In many ways, they are one of the last pockets where the risk of cardiovascular death has not been reduced,” says Vlado Perkovic, a nephrologist at the University of New South Wales in Sydney, Australia, and a co-leader of the trial. The availability of semaglutide as a potential treatment could be game-changing, he says.
Historically, physicians have treated chronic kidney disease with drugs including blood-pressure medication. But these treatments offer only limited protection for the kidneys. In the past decade, options have expanded. For instance, researchers have demonstrated2 that a class of diabetes drug called sodium-glucose co-transporter-2 (SGLT2) inhibitors can slow the progression of chronic kidney disease, as well as protect against major cardiovascular incidents.
But “there’s still substantial residual risk in this population”, Tuttle says. Diabetic kidney disease is the leading cause of chronic kidney disease worldwide, accounting for 50% of kidney-failure cases in wealthy countries. “There is a need for more therapies,” she adds.
A focus on kidneys
Scientists already knew from other trials that semaglutide, which moderates blood sugar, can help to protect the kidneys, says Hertzel Gerstein, an endocrinologist at McMaster University in Hamilton, Canada. But those trials were testing the drug’s effect on other conditions, such as heart disease, and clinicians just happened to notice kidney benefits.
What’s special about the latest trial is that it is the first to focus on the progression of kidney disease, Gerstein says.
The trial also hinted that semaglutide could slow the degradation of a person’s kidneys. Participants receiving the drug maintained a healthier ‘estimated glomerular filtration rate’, which is a measure of the kidneys’ ability to filter waste, and had lower amounts of a protein called albumin in their urine than did those receiving placebo. High levels of the protein are a sign of leaky blood vessels in the kidneys and point to kidney function declining.
Why exactly semaglutide benefits the kidneys is still unclear, say the researchers who conducted the trial. It could have multiple mechanisms, including reducing inflammation in the kidneys, but more tests are needed.
Other major questions remain, including whether semaglutide will offer a similar benefit to people who have chronic kidney disease, but who are not diabetic. Researchers must also find out how it stacks up against other medications used to treat chronic kidney disease, such as SGLT2 inhibitors, and whether combining these drugs can offer further benefits.
