Oral semaglutide, the first oral GLP-1 receptor agonsist, was approved by the FDA on Sept 20, 2019, becoming the only noninjectable formulation in the class.
The FDA on Friday approved oral semaglutide (Rybelsus), the first noninjectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) for treatment of type 2 diabetes (T2D), as stated in an agency press release.
FDA evaluated results of several large clinical trials of oral semaglutide (Novo Nordisk) that demonstrated superior A1c reductions vs placebo (PIONEER 4) and against other common hyperglycemic agents, ie, empagliflozin (oral SGLT2 inhibitor; PIONEER 2) and sitagliptin (oral DPP-4 inhibitor; PIONEER 3). In all, 10 PIONEER clinical trials were conducted which included 9543 adults with T2D, according to a Novo Nordisk press release. The release notes that across the PIONEER trials, oral semaglutide also was associated with up to a 4.4 kg reduction in body weight.
In studies of oral semaglutide vs placebo, 69% of patients assigned to 7 mg oral semaglutide and 77% of patients assigned to 14 mg oral semaglutide decreased their HbA1c to 7% or lower at 26 weeks, compared with 31% of patients assigned placebo, according to the FDA.
“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,” Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research, said in the release. “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.”
Quoted in a Novo Nordisk press release, Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women's Hospital in Boston and a PIONEER clinical trial investigator said, “The availability of an oral GLP-1 receptor agonist represents a significant development, and primary care providers, specialists and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals.” Aroda noted that the injectable GLP-1 RAs are currently underutilized in clinical practice.
In PIONEER 6, the required cardiovascular safety study under current FDA policy for novel diabetes drugs, oral semaglutide was found to have a similar safety profile to the inejctable formulation.
There are some restrictions to use of the oral GLP-1 RA including that it must be taken at least 30 minutes before the first food, beverage or other oral medication of the day with no more than 4 oz plain water. The most common adverse effects are similar to those seen with the injectable GLP-1 RA agents ie, nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.
Labeling for oral semaglutide also carries class warnings regarding an increased risk for thyroid C-cell tumors, and that semaglutide is not recommended as the first choice of medicine for treating diabetes.