A global phase 3a trial successfully demonstrated greater reductions in HbA1c and body weight with a oral semaglutide drug treatment than with dulaglutide, as well as a a comparable number of adverse events in 458 Japanese adults with type 2 diabetes between these medications. The 57-week randomized PIONEER 10 trial compared 3mg, 7mg, and 14 mg oral semaglutide versus 0.75 mg of once-weekly subcutaneous dulaglutide, a dosage approved by Japan’s Pharmaceutical and Medical Devices Agency.1

During the PIONEER 10 trial, which tested the safety, tolerability and efficacy of oral semaglutide, both drugs were used in combination with 1 oral antidiabetic drug, according to Novo Nordisk, whose officials announced the study results Thursday, in a prepared statement. Oral semaglutide is an investigational GLP-1 analogue taken once daily as a tablet. The FDA approved a pre-filled pen version of Novo Nordisk’s semaglutide in late 2017.2
 
Click to read more about Novo Nordisk's once-weekly semaglutide approved by the FDA.

Prior to enrollment in the PIONEER 10 trial, study participants were inadequately controlled on 1 oral antidiabetic drug.1

"Many people with type 2 diabetes in Japan remain uncontrolled on oral antidiabetic treatments," said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, in a prepared statement.1 "When adding oral semaglutide to the treatment of this group of people, this study has demonstrated that oral semaglutide is both well tolerated and more efficacious compared to subcutaneous dulaglutide."

The most frequently reported adverse events were constipation and nausea. The proportion of people treated with 3, 7 and 14 mg oral semaglutide who experienced gastrointestinal adverse events were 31%, 39% and 54%, respectively, compared to 40% with dulaglutide. The proportion of people who discontinued treatment due to adverse events was between 3% and 6% of people treated with oral semaglutide, compared to 3% of people treated with dulaglutide.1
 
Two distinct statistical approaches to evaluating the efficacy of oral semaglutide versus dulaglutide were applied in the PIONEER 10 trial: a primary statistical approach evaluating the effect, regardless of discontinuation of treatment and use of rescue medication, and a secondary statistical approach describing the effect while on treatment and without use of rescue medication.1
 
According to Novo Nordisk, the primary statistical approach showed significantly greater reductions in HbA1c and body weight with oral semaglutide 14 mg compare to 0.75 mg dulaglutide at week 52. 
 
When applying the secondary statistical approach, from a baseline of 8.3%, people treated with 14 mg oral semaglutide experienced a statistically significantly greater reduction in HbA1c of 1.8% compared to 1.3% with 0.75 mg dulaglutide after 52 weeks. The reductions in HbA1c were 0.7% and 1.4% for people treated with 3 and 7 mg oral semaglutide, respectively. Reductions in body weight from baseline were also statistically significantly greater with 14 mg oral semaglutide at week 52, with a reduction of 1.9 kg compared to a weight gain of 1.1 kg with dulaglutide. People treated with 3 and 7 mg oral semaglutide experienced a weight gain of 0.1 kg and weight reduction of 1.0 kg, respectively.1
 
In addition, applying the secondary statistical approach, The Japanese Diabetes Society treatment target of HbA1c below 6.5% was achieved by 21%, 43% and 58% of people on treatment with 3, 7 and 14 mg oral semaglutide, respectively, compared to 41% of the people treated with 0.75 mg dulaglutide.1
 
The PIONEER 10 trial is part the PIONEER phase 3a clinical development program for oral semaglutide. The program has a global enrollment of 8,845 people with type 2 diabetes across 10 clinical trials, which are all expected to completed in 2018.1

A previous clinical trial, PIONEER 1, demonstrated a significant and superior improvement in glycated hemoglobin (A1C) for all 3 doses of oral semaglutide compared with a placebo, according to the American Journal of Managed Care. In that trial, the American Diabetes Association treatment target of A1C below 7% was achieved by 59%, 72%, and 80% of people treated with 3 mg, 7 mg, and 14 mg doses, respectively, compared with 34% of people treated with placebo.2
 
Click to read more about the PIONEER 1 clinical trial at AJMC.com.

Reference
  1. Novo Nordisk - Oral semaglutide demonstrates greater reductions in HbA1c and body weight and comparable number of adverse events vs dulaglutide in Japanese people with type 2 diabetes [news release]. Bagsvaerd, Denmark; September 20, 2018: Novo Nordisk. Accessed September 20, 2018.
  2. Grande S. Novo Nordisk Announces Phase 3a Trial Results for Oral Semaglutide. American Journal of Managed Care. AJMC.com. Published February 26, 2018. Accessed September 20, 2018.