Among patients with type 2 diabetes in need of therapy intensification, treatment with oral semaglutide 25mg and 50mg was associated with superior reductions in hemoglobin A1c (HbA1c) and weight loss compared with the 14mg dose, according to results from the phase 3b PIONEER PLUS trial.
The PIONEER PLUS trial (ClinicalTrials.gov Identifier: NCT04707469) included over 1200 patients 18 years of age and older with type 2 diabetes who were currently on a stable dose of 1 to 3 oral antidiabetic medications (eg, metformin, sulfonylureas, and/or SGLT2 inhibitors). Patients had a mean baseline HbA1c of 9.0% and a mean baseline body weight of 96.4kg. The study participants were randomly assigned to receive semaglutide 25mg, 50mg, or 14mg orally once daily for 68 weeks.
According to the trial product estimand (the effect if all participants adhered to treatment as intended), patients treated with the 25mg and 50mg doses achieved statistically significant and superior HbA1c reductions of 1.9 and 2.2 percentage points, respectively, compared with a reduction of 1.5 percentage points with the 14mg dose. The 25mg and 50mg doses were also associated with statistically significantly greater weight loss (-7.0kg and -9.2kg, respectively, vs -4.5kg with the 14mg dose).
All dosage strengths of oral semaglutide were reported to be safe and well tolerated. Mild to moderate gastrointestinal adverse reactions were most commonly observed during the study.
“We are pleased to see the results from the PIONEER PLUS trial which add further evidence of the benefits of oral semaglutide for people living with type 2 diabetes,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “The higher efficacy from 25mg and 50mg doses provides the option to progress to higher doses if additional glycemic control or weight loss are needed”.
Oral semaglutide is currently marketed under the brand name Rybelsus® as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Rybelsus is available in 3mg, 7mg, and 14mg oral tablets. The Company plans to file for regulatory approval of the 25mg and 50mg dosage strengths in 2023.
Oral semaglutide 25 mg and 50 mg demonstrate superior reductions in HbA1c and body weight versus 14 mg in people with type 2 diabetes in the PIONEER PLUS phase 3 trial. News release. Novo Nordisk. Accessed March 24, 2023. https://www.globenewswire.com/news-release/2023/03/24/2634147/0/en/Oral-semaglutide-25-mg-and-50-mg-demonstrate-superior-reductions-in-HbA1c-and-body-weight-versus-14-mg-in-people-with-type-2-diabetes-in-the-PIONEER-PLUS-phase-3-trial.html.