Findings from two key clinical trials have demonstrated the efficacy and safety of an oral formulation of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide for the treatment of obesity and type 2 diabetes. A panel of investigators presented the primary results of the phase 3 OASIS 1 and PIONEER PLUS trials during the 83rd Scientific Sessions.
“Oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” said Filip K. Knop, MD, PhD, Professor of Endocrinology and Director of the Center for Clinical Metabolic Research at Gentofte Hospital, University of Copenhagen, Denmark.
The session, Oral Semaglutide for Treatment of Obesity and Type 2 Diabetes—Results from OASIS 1 and PIONEER PLUS Trials, can be viewed on-demand by registered meeting participants at ADA2023.org. If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28.
OASIS 1 was a double-blind, randomized, controlled, phase 3 superiority trial in which investigators assessed the efficacy and safety of a 68-week treatment with the once-daily oral GLP-1 analog semaglutide versus placebo for overweight or obesity in adults without type 2 diabetes.
Co-primary endpoints were the percentage change in body weight and the achievement of weight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other weight-lowering therapies.
“The OASIS 1 trial showed that oral semaglutide once daily in a 50 mg dose was superior to placebo from baseline to week 68 for all co-primary and all confirmatory secondary endpoints, and they were all highly statistically significant,” Dr. Knop said. “The overall safety profile of oral semaglutide was consistent with the safety profile for semaglutide and the GLP-1 receptor agonist class in general.”
Findings from the OASIS 1 study were presented at the 83rd Scientific Sessions and published in The Lancet simultaneously.
“In terms of the trial rationale, studies with GLP-1 receptor agonists have shown very consistently a dose-response effect on body weight loss with higher dosages, and once-daily formulations of semaglutide 7 mg and 14 mg have been approved for the treatment of type 2 diabetes and does provide clinically relevant weight loss,” said Julio Rosenstock, MD, Director of Velocity Clinical Research at Medical City Dallas and Clinical Professor of Medicine at the University of Texas (UT) Southwestern. “The availability of an oral GLP-1 with weight-lowering efficacy could potentially give people requiring treatment for obesity and their physicians a great option for choice of treatment.”
PIONEER PLUS compared three doses of oral semaglutide—14 mg daily, 25 mg daily, or 50 mg daily—versus placebo in 1,606 individuals with type 2 diabetes.
“Dose-dependent reductions in A1C and body weight at higher doses in people with type 2 diabetes have been demonstrated in the phase 2 evaluation of oral semaglutide, suggesting that oral semaglutide at higher doses may provide a more individualized treatment option in people with type 2 diabetes who need additional glycemic control and/or additional weight reduction,” explained Sue Pedersen, MD, FRCPC, Specialist in Endocrinology and Metabolism at C-ENDO Diabetes & Endocrinology Clinic, Calgary, Canada. “PIONEER PLUS was therefore designed to evaluate the efficacy, safety, and tolerability of oral semaglutide at doses of 25 mg and 50 mg once daily, compared with the 14 mg once-daily dose that is already in clinical use.”
Primary outcome measures included change in A1C from baseline to week 52 and from baseline to week 68. Secondary endpoints included change in body weight, fasting plasma glucose, body mass index, A1C of less than 7% and equal to or less than 6.5%, change in waist circumference, weight loss equal to or greater than 5% and 10%, changes in lipid profiles, and changes in diastolic and systolic blood pressure over the same two periods.
“The PIONEER PLUS trial showed superior glycemic control and body weight loss and improvement in the cardiometabolic risk factor profile with higher doses of once-daily oral semaglutide at 25 mg and 50 mg per day compared with the currently approved 14 mg dose for people with type 2 diabetes,” said Vanita R. Aroda, MD, Director of Diabetes Clinical Research, Brigham and Women’s Hospital, and Associate Professor of Medicine at Harvard Medical School. “Higher doses of oral semaglutide were overall well-tolerated with a safety profile consistent with what we know of the GLP-1 receptor agonist class. Looking to the future, oral semaglutide 25 mg and 50 mg doses could be a beneficial option to support individualized treatment goals for persons with type 2 diabetes in need of treatment intensification.”
Findings from the PIONEER PLUS study also were published simultaneously in The Lancet.
Sean Wharton, MD, PharmD, Medical Director of the Wharton Medical Clinic and Adjunct Professor at McMaster University in Hamilton and York University, Toronto, Canada, concluded the presentations with an independent commentary on how the OASIS 1 and PIONEER PLUS trial findings may impact the landscape of obesity treatment and type 2 diabetes management.
“Obesity is a pandemic. There is no single chronic metabolic disease that is more prevalent than obesity, and approximately 90% of people with type 2 diabetes have obesity,” Dr. Wharton said. “Oral medications for obesity can be made, shipped, and administered easily. They may cost less, be more available, and may improve access and equity. Additionally, oral medications for obesity will give more options for adolescents and children and may impact polygenic obesity risk. The magnitude of weight loss with the new agents is very good and getting better—30% is coming.”