Results from the first phase 3 trial for an oral form of the GLP-1 receptor agonist semaglutide show the drug is safe and effective for patients with poorly controlled type 2 diabetes, with 80% of patients assigned the highest dose reaching HbA1c 7% or less over 26 weeks, Novo Nordisk announced in a press release.
In announcing headline results for PIONEER 1, the first phase 3a trial for once-daily, oral semaglutide, the company noted that participants assigned the drug experienced a reduction in both body weight and HbA1c compared with patients assigned placebo, with most patients reporting only mild to moderate nausea that diminished over time.
“We are very encouraged by the results of the PIONEER 1 trial, which confirm the unprecedented oral efficacy of semaglutide that was reported in the phase 2 clinical trial in type 2 diabetes,” Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said in a statement. “We look forward to providing data from the remaining nine PIONEER trials throughout this year and an expected regulatory submission in 2019.”
In a global randomized, double-blind, placebo-controlled, parallel group study, researchers analyzed the safety and efficacy of three doses of oral semaglutide vs. placebo in 703 adults with type 2 diabetes treated with diet and exercise only (mean baseline HbA1c, 8%; mean baseline BMI, 31.8 kg/m²; mean baseline body weight, 88 kg). Researchers randomly assigned patients 1:1:1:1 to receive 3 mg, 7 mg or 14 mg daily semaglutide or placebo for 26 weeks. Primary endpoint was change in HbA1c from baseline to week 26.
Over 26 weeks, patients assigned 3-mg, 7-mg and 14-mg doses achieved mean HbA1c reductions of 0.8%, 1.3% and 1.5%, respectively, vs. a 0.1% reduction with placebo. The American Diabetes Association treatment target of HbA1c below 7% was achieved by 59%, 72% and 80% of patients assigned the 3-mg, 7-mg and 14-mg doses, respectively.
Across all three semaglutide doses, patients experienced a reduction in body weight over 26 weeks; however, weight loss for the 3-mg and 7-mg doses did not reach statistical significance, according to researchers. Mean weight loss for patients in the 14-mg dose arm was 4.1 kg, compared with mean 1.5-kg weight loss for patients assigned placebo.
Researchers reported that between 5% and 16% of patients assigned semaglutide reported mild to moderate nausea vs. 6% assigned placebo. Between 2% and 7% of patients assigned semaglutide discontinued treatment due to adverse events vs. 2% assigned placebo.
The results for oral semaglutide follow several successful trials of a once-weekly, injectable form of semaglutide (Ozempic). In findings from the SUSTAIN 7 program previously reported in Endocrine Today, patients assigned subcutaneous semaglutide 0.5 mg or 1 mg experienced greater reductions in HbA1c and body weight compared with those assigned to dulaglutide 0.75 mg or 1.5 mg. The cardiovascular outcomes trial SUSTAIN 6 demonstrated a reduction in CV risk compared with placebo, as an add-on to standard of care in patients with established CVD. The FDA approved once-weekly semaglutide in October.
The PIONEER phase 3 program for oral semaglutide is expected to enroll more than 9,000 adults with type 2 diabetes across 10 clinical trials, all of which are expected to be complete by 2018, according to Novo Nordisk.