The investigative GLP-1 receptor agonist was compared to liraglutide, sitagliptin, and placebo in adult patients with type 2 diabetes.
A pair of phase 3a studies from Novo Nordisk have reported that oral glucagon-like peptide-1 (GLP-1) analogue semaglutide was capable of greater glycated hemoglobin (HbA1c) and body weight reduction versus marketed competitors in adults with type 2 diabetes (T2D).
The supplemental analysis from the PIONEER 4 and PIONEER 7 studies indicated the therapy fared better in treating these symptoms than that of liraglutide (Victoza) and sitagliptin (Januvia). With a subcutaneous form of the investigative drug (Ozempic) gaining US Food and Drug Administration (FDA) approval for adults with T2D last month, the new results hold promise for Novo Nordisk’s oral therapy.
In the PIONEER 4 trial, oral semaglutide was compared to liraglutide and placebo in 711 patients with T2D that had been inadequately controlled by metformin, with or without a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. At 26 weeks, semaglutide patients achieved non-inferior reduction in HbA1c compared to liraglutide, and significant-to-superior reductions in HbA1c levels and body weight at compared to placebo.
In PIONEER 7, semaglutide was compared to sitagliptin in 504 people with T2D that had been inadequately controlled on 1 or 2 oral antidiabetic therapies. Patients on semaglutide achieved significant-to-superior HbA1c treatment target levels — as set by the American Diabetes Association (ADA) — below 7% at week 52. Patients on the therapy also demonstrated reductions in body weight compared to sitagliptin.
The most common adverse event reported in patients given semaglutide in either trial was nausea, which was prevalent in 20% and 21% of patients in PIONEER 4 and PIONEER 7, respectively. Another 11% and 9% of patients administered semaglutide in the respective studies discontinued the treatment due to adverse events, while just 9% of patients on liraglutide and 3% on sitagliptin discontinued treatment.
The new data comes a month after Novo Nordisk reported phase 3a PIONEER 2 study results, which reported that once-daily oral semaglutide had superior improvement in T2D adults’ HbA1c levels compared to SGLT-2 inhibitor empagliflozin (Jardiance).
Including glycemic control and weight loss reduction, semaglutide and its fellow members of the GLP-1 receptor agonist class have also shown benefits in cardiovascular intervention. Eliot Brinton, MD, president of the Utah Lipid Center in Salt Lake City, UT, told MD Mag that it’s a promising time for the field, as therapies that can lower glucose levels are on the rise, and drugs that can also influence cardiovascular risk are joining the ranks.
“It's a very exciting time to be treating diabetes as we're now better empowered to address the question of how do we not only reduce glucose and keep that under control, but how do we also reduce cardiovascular disease, which is the number one cause of both death and disability in patients with type 2 diabetes,” Brinton said.
The PIONEER 3 trial, which is comparing 3 different dose levels of oral semaglutide to sitagliptin, will have reported analysis before the end of Q2 this year, according to Novo Nordisk.