A pooled analysis of 5 PIONEER trials presented by John Buse, MD, at ADA 2020 is shedding new light on the impact of oral semaglutide based on background glucose-lowering therapy.
John Buse, MD
A potential game-changer for patients with diabetes, results from an analysis of the PIONEER program indicates reductions in HbA1c and body weight seen with oral semaglutide (Rybelsus) were similar regardless of the background medication of patients.
Presented at the American Diabetes Association’s (ADA) 80th Scientific Sessions, results of the analysis support use of the oral GLP-1 receptor agonist in combination with other glucose-lowering agents in patients with type 2 diabetes.
“Background medication did not appear to influence the relative benefit versus comparator of oral semaglutide to reduce hemoglobin A1c and body weight,” said John Buse, MD, director of the North Carolina Translational and Clinical Sciences Institute and of the Diabetes Center at the University of North Carolina School of Medicine, during his presentation at ADA 2020. “In addition, in the majority of subgroups these reductions were greater with oral semaglutide than the comparators.”
In an effort to assess the effects of oral semaglutide on HbA1c and body weight, investigators designed an exploratory subgroup analysis to examine the effect of background medications in 5 of the 8 PIONEER trials. Using data from the PIONEER 3, 4, 5, 7, and 8, investigators hoped to analyze effects in patients who received once-daily oral semaglutide at 14 mg or flexibly-dosed against study comparators, which included sitagliptin, liraglutide or placebo, based on the patient’s use of metformin, sulfonylurea, SGLT2 inhibitors, insulin, or combinations of the aforementioned therapies.
From these trials, investigators identified a cohort of 2836 patients for inclusion in their analysis. Of note, baseline characteristics similar between the various subgroups established from this patient population.
Upon analysis, results indicated reductions in HbA1c seen with oral semaglutide were similar across all background medications—noting background medication only had a significant impact on change in HbA1c in PIONEER 8. During PIONEER 8, the observed treatment difference seen between oral semaglutide and placebo was smaller in patients receiving concurrent insulin and metformin compared with insulin alone.
In regard to body weight, investigators found reductions associated with oral semaglutide varied slightly across background medications subgroups but there was no discernible pattern.
Overall, HbA1c and weight loss were greater with oral semaglutide compared with comparators, regardless of background mediation subgroups, except when compared against liraglutide 1.8 mg in PIONEER 4. In PIONEER 4, liraglutide use results in similar HbA1c reductions to what was seen with oral semaglutide.
“This suggests that oral semaglutide can be used to improve diabetes outcomes in combination with other commonly used treatments in a broad population of patients,” added Buse during his presentation.
This study, “Efficacy of Oral Semaglutide According to Background Medication: An Exploratory Subgroup Analysis of the PIONEER Trial Program,” was presented at ADA 2020.