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First phase 3 results for high-dose oral semaglutide to be released in San Diego


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4 minutes

Vanita R. Aroda, MD
Vanita R. Aroda, MD

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as one of the most effective treatments for type 2 diabetes and obesity. The primary results of the latest phase 3 trials of higher doses of an oral formulation of semaglutide will be released during the 83rd Scientific Sessions in San Diego.

“These two trials, OASIS 1 and PIONEER PLUS, are testing high-dose oral GLP-1 receptor agonists for both type 2 diabetes and obesity, which is novel for the field,” said principal investigator Vanita R. Aroda, MD, Director of Diabetes Clinical Research, Brigham and Women’s Hospital, and Associate Professor of Medicine at Harvard Medical School. “The first GLP-1 receptor agonist was approved for the treatment of type 2 diabetes back in 2005 and was initially only available as injectable medications. As injectables, they have traditionally not often been offered as early therapy when they could be highly effective.”

Oral Semaglutide for Treatment of Obesity and Type 2 Diabetes – Results from OASIS 1 and PIONEER PLUS Trials will take place on Sunday, June 25, at 4:30 p.m. PT in Ballroom 20A-C of the San Diego Convention Center. This session also will be available via livestream for registered meeting participants. Investigators will discuss results from these two key trials and provide an assessment of where the trials fit into the current clinical context of type 2 diabetes and obesity.

As effective as GLP-1 receptor agonists such as semaglutide have been for individuals with type 2 diabetes or who are overweight or obese without type 2 diabetes, these agents have not been as widely used in primary care, Dr. Aroda noted. The injectable GLP-1 receptor agonists have more often been used after other oral approaches and historically have been treated as a specialty medication not unlike insulin.

“What we have come to appreciate over time is that the GLP-1 receptor agonist class is highly efficacious and goes beyond just glucose lowering in people with type 2 diabetes,” she said. “We see a high degree of being able to help patients get to their treatment goals, and particularly with more recent medications, a high degree of meaningful weight loss that also contributes to the overall picture of health and morbidity. Many cardiovascular outcomes trials have also shown reductions in cardiovascular disease outcomes with GLP-1 receptor agonists in patients at risk. Having a higher dose of an effective GLP-1 receptor agonist allows clinicians to further individualize treatment for the person with type 2 diabetes.” 

OASIS 1 aimed to evaluate a dose of 50 mg daily oral semaglutide versus placebo for weight loss in 660 individuals who are overweight or obese and do not have type 2 diabetes. The primary outcome was relative change in body weight from baseline to week 68. Secondary endpoints included body weight reductions greater than or equal to 10% and 15%, change in physical function as assessed by two different instruments, change in waist circumference, change in body mass index (BMI), and change in systolic blood pressure.

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. The current maximum approved dose of oral semaglutide is 14 mg daily.

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 trial cohorts in both OASIS 1 and PIONEER PLUS were similar to cohorts in other trials of semaglutide and other GLP-1 receptor agonists, Dr. Aroda said. The similarities between trial cohorts, designs, and outcome measures across these two programs and historical data should help the diabetes community better contextualize the results.

“The ways we are treating both diabetes and obesity are changing very quickly, in part because the therapeutics themselves have shed light on the support we can meaningfully offer our patients,” Dr. Aroda said. “This session will put you in the front row to see the primary data—the overall picture of efficacy and safety—to better understand where these medications might fit to support our patients and their clinical care teams.”