Novo Nordisk on Saturday said its diabetes pill Rybelsus showed cardiovascular benefits in a late-stage trial, paving the way for it to become a new treatment option for people living with diabetes and heart disease.
The pill lowered the risk of cardiovascular-related death, heart attack and stroke by 14% compared to a placebo after four years on average in patients with diabetes and established heart disease, with or without chronic kidney disease. The Danish drugmaker presented the results on Rybelsus, which is already approved for Type 2 diabetes, at the American College of Cardiology’s Annual Scientific Session in Chicago.
Novo Nordisk has already applied in the U.S. and EU to expand the pill’s approval to include lowering the risk of serious cardiovascular complications, Stephen Gough, the company’s global chief medical officer, said in an interview.
Rybelsus is the once-daily oral formulation of Novo Nordisk’s blockbuster diabetes injection Ozempic, which is taken once a week. Both treatments, as well as the company’s weekly weight loss injection Wegovy, contain the active ingredient semaglutide.
Wegovy in March 2024 won U.S. approval for slashing the risk of major cardiovascular events in adults with cardiovascular disease and who are obese or overweight. But the pill data presented on Saturday suggests that patients who are hesitant to take injections, such as those who are afraid of needles, could soon access treatment in a more convenient way.
“We know not everybody wants an injection, whether it is painful or not, they want the option of an oral medication,” Gough told CNBC. “We provide that option, that you can have one or the other, depending on what the patients and the healthcare professional think is right in that joint discussion.”
The data comes as a slate of other drugmakers, including Eli Lilly, work to develop oral GLP-1s for diabetes, weight loss and other conditions, such as sleep apnea.
The phase three trial examined just over 9,600 patients 50 years and older who received either Rybelsus or placebo, both on top of their standard treatment regimen, for an average of just under four years. Nearly half of all patients received medications called SGLT2 inhibitors, which are primarily used to lower blood sugar in adults with Type 2 diabetes, at some point during the trial.
By the end of the trial, 12% of people taking Rybelsus and 13.8% of those taking placebo experienced cardiovascular-related death, heart attack or stroke. That represents a 14% overall lower risk among those who took Rybelsus.
Researchers said that the reduced risk is in line with the cardiovascular benefits observed in eight previous trials involving injectable GLP-1s, which include semaglutide and other popular medications, according to a release from the American College of Cardiology. GLP-1s mimic certain gut hormones to tamp down appetite and regulate blood sugar, but also have other effects such as reducing inflammation.
Rybelsus helped lower the risk of non-fatal heart attacks by 26% compared to the placebo, which was “the primary driver” of the overall reduction of risk for cardiovascular complications in the trial, the release said. The pill also slashed the risk of non-fatal strokes by 12% and cardiovascular-related death by 7% compared to placebo.
There was no significant difference between the Rybelsus and placebo groups in outcomes related to kidney function, the release added. But the trial was “clearly” designed to examine the cardiovascular rather than kidney benefits of the pill, Gough said.
Ozempic is already approved to treat chronic kidney disease in diabetes patients.
The most common side effects reported in the study were gastrointestinal issues, such as nausea, diarrhea and constipation, which rarely led patients to stop taking Rybelsus, according to the release. Those symptoms are consistent with the side effects of injectable semaglutide.
Similar results were seen across all subgroups of patients – by age, sex and among people with different health conditions at the start of the trial, the release said.
Unlike its injectable counterparts, Rybelsus must be taken on an empty stomach at least 30 minutes before breakfast with a small amount of water. Despite those requirements, the study offers “reassurance that patients were able to take the drug as directed and reap cardiovascular health benefits from it,” said Dr. Darren McGuire, professor of medicine at UT Southwestern Medical Center and the study’s first author.