PIONEER 1, the first phase 3a trial with oral semaglutide for treatment of adults with type 2 diabetes (T2DM), achieved the primary endpoint of change in HbA1c from baseline to week 26 . Oral semaglutide is a new GLP-1 analogue taken once daily as a tablet. The global 26-week trial investigated the efficacy and safety of 3, 7 and 14 mg oral semaglutide compared with placebo in 703 people with T2DM, treated with diet and exercise only.

Two distinct approaches to evaluate the effect of oral semaglutide were applied in the PIONEER 1 trial; a primary statistical principle required by recent regulatory guidelines evaluating the effect regardless of treatment adherence and a secondary statistical principle describing the effect if people had adhered to treatment and did not initiate rescue medication.

The trial achieved its primary objective according to the primary statistical principle by demonstrating significant and superior improvements in HbA1c for all three doses of oral semaglutide compared to placebo. Moreover, the 14 mg dose of oral semaglutide demonstrated significant and superior weight loss versus placebo, weight loss was observed for the 7 mg and 3 mg doses but did not reach statistical significance.

Applying the secondary statistical principle, people treated with 3, 7 and 14 mg oral semaglutide achieved reductions in HbA1c of 0.8%, 1.3% and 1.5%, respectively, compared to a reduction of 0.1% in people treated with placebo from a mean baseline of 8.0%. The American Diabetes Association (ADA) treatment target of HbA1c below 7.0% was achieved by 59%, 72% and 80% of people on treatment with 3, 7 and 14 mg oral semaglutide, respectively, compared to 34% of the people treated with placebo. In addition, from a mean baseline body weight of 88 kg and a BMI of 31.8 kg/m2, people treated with 3, 7 and 14 mg oral semaglutide experienced a weight loss of 1.7 kg, 2.5 kg and 4.1 kg, respectively, compared to a weight loss of 1.5 kg in people treated with placebo.

In the trial, oral semaglutide appeared to have a safe and well-tolerated clinical profile. The most common adverse event for all three oral semaglutide doses was mild to moderate nausea, which diminished over time. Between 5% and 16% of people treated with oral semaglutide experienced nausea, compared to 6% of people treated with placebo. Premature treatment discontinuation due to adverse events ranged from 2% to 7% for people treated with oral semaglutide, compared to 2% for people treated with placebo.

The PIONEER phase 3a clinical development program for oral semaglutide is a global development program with an expected enrolment of more than 9,000 people with type 2 diabetes across 10 clinical trials, which all are expected to complete in 2018.

Source: Press release Novo Nordisk, February 22, 2018