WASHINGTON -- The FDA , to be sold under the brand name Rybelsus, for treatment of type 2 diabetes in adults.
The decision caps several years of effort by drugmaker Novo Nordisk to show that semaglutide can be delivered by mouth without sacrificing efficacy, which has been a perennial problem for peptide agents. In all, Novo had conducted 10 phase III trials in support of the oral formulation.
Oral semaglutide thus becomes the first glucagon-like peptide-1 (GLP-1) agonist to reach market, and comes at doses of 7 mg and 14 mg.
Its specific indication is to improve glycemic control and should be accompanied by lifestyle changes including diet and physical activity, the FDA noted.
"Patients want effective treatment options for diabetes that are as minimally intrusive on their lives as possible, and the FDA welcomes the advancement of new therapeutic options that can make it easier for patients to control their condition," said Lisa Yanoff, MD, acting director of the Division of Metabolism and Endocrinology Products in the FDA's Center for Drug Evaluation and Research, in the agency's approval announcement. "Before this approval, patients did not have an oral GLP-1 option to treat their type 2 diabetes, and now patients will have a new option for treating type 2 diabetes without injections."
Approval was heavily influenced by results from randomized trials showing that oral semaglutide reduced HbA1c more than was seen with placebo and was as effective as GLP-1 injection treatments. In one of the placebo-controlled studies, 69% of those on the 7 mg per day dose and 77% of those taking the drug at 14 mg per day achieved HbA1c levels below 7%, compared with 31% of the placebo group.
Although not mentioned in the FDA’s statement, one of the most impressive studies backing oral semaglutide was the PIONEER 3 trial testing the agent head-to-head with the DPP-4 inhibitor sitagliptin (Januvia). That study, reported earlier this year, found significantly greater reductions in HbA1c with oral semaglutide, by 0.3 to 0.5 percentage points.
Still showed oral semaglutide at 14 mg per day to be superior to the SGLT-2 inhibitor empagliflozin (Jardiance) at 25 mg/day for the endpoint of HbA1c lower than 7.0%.
One important question for all new diabetes drugs involves cardiovascular safety. For oral semaglutide, the FDA-required trial showed it was on par with the previously approved injectable form (Ozempic). Although that placebo-controlled study didn’t show a statistically significant reduction in cardiovascular events, as trials with several other diabetes drugs have done, the point estimate suggested a 21% lower risk for major events.
The drug's label will include a boxed warning about risk of thyroid C-cell tumors, and will note that it is not recommended as first-line therapy.