Oral Semaglutide Offers Superior A1C Reduction, Weight Loss in PIONEER 5 Trial

Novo Nordisk today announced that topline results for its phase 3a trial of oral semaglutide show the drug reduced glycated hemoglobin (A1C) and helped patients with type 2 diabetes (T2D) lose weight after 26 weeks. If successful, the drug would be the first glucagon-like peptide-1 (GLP-1) taken once daily as a tablet.

PIONEER 5 is 1 of 10 trials involving the study drug. An injectable form of semaglutide, sold as Ozempic, received FDA approval last year.

Results of the PIONEER 5 trial, which involved 324 people with T2D and moderate renal impairment, showed that those treated with 14 mg oral semaglutide saw an A1C reduction of 1.1%, compared with 0.1% for placebo. The group taking the study drug lost 3.7 kg compared with 1.1 kg with placebo.

From an average baseline A1C of 8.0%, the share of people reaching the target A1C of 7.0% by week 26 was greater with oral semaglutide than with placebo: 64%, compared with 21%. A target of 7.0% is recommended by the American Diabetes Association and other major diabetes professional organizations, as well as the Joslin Diabetes Center.

An earlier trial in the PIONEER program tested oral semaglutide at different doses.

According to the statement from Novo Nordisk, PIONEER 5 involved 2 statistical approaches:

• A primary approach required by regulatory guidance that evaluates the drug’s effect, regardless of discontinuation of treatment or use of rescue medication. During the trial, 15% discontinued treatment due to adverse events, primarily nausea, compared with 6% who discontinued while taking placebo.
• A secondary approach described the effect of the drug while on treatment, without the use of rescue medication.

The population in PIONEER 5 had T2D and moderate renal impairment inadequately controlled with metformin, sulfonylurea alone or in combination with metformin, or basal insulin alone or in combination with metformin.

“The results from PIONEER 5 showed that oral semaglutide is efficacious and has a solid safety profile in people with type 2 diabetes and moderate renal impairment, thereby further expanding the solid clinical profile of oral semaglutide,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer, Novo Nordisk.

“Renal impairment is a serious diabetes complication and people with this condition have limited oral anti-diabetic treatment options,” he said. “If approved, oral semaglutide represents an efficacious new solution.”