Promising phase II results for oral semaglutide
medwireNews: Phase II findings show that daily oral semaglutide provides glycemic control that is significantly better than that of placebo and, at the highest doses, is similar to that achieved with weekly injectable semaglutide.
The adverse event profile of oral semaglutide was in line with that of injectable glucagon-like peptide (GLP)-1 receptor agonists, report Melanie Davies (University of Leicester, UK) and co-researchers in JAMA.
The most common adverse events were gastrointestinal, which were mainly mild or moderate and most frequently nausea, which was reported by between 13% and 37% of patients taking oral semaglutide, depending on the dose, and by 32% of those taking injectable semaglutide, compared with 1% of the placebo group. Diarrhea occurred in up to 20% of patients taking semaglutide and 10% of the placebo group.
There were three cases of pancreatitis, all in patients taking semaglutide. The researchers note that this has “also been reported in the clinical development programs for other incretin-based therapies,” but not in longer-term studies of semaglutide and liraglutide.
Heart rate also increased in patients taking semaglutide, as reported for other GLP-1 receptor agonists. However, trials to date support a positive, or at least neutral, cardiovascular effect in the long term.
“The oral formulation of semaglutide may improve acceptance and adherence for some patients compared with the injectable formulation of GLP-1 receptor agonists,” comment the researchers.
The trial included 632 patients with type 2 diabetes who had glycated hemoglobin (HbA1c) levels of 7.0% to 9.5% despite metformin treatment. Those taking oral semaglutide were randomly assigned to receiving starting doses of 2.5 or 5.0 mg per day, which was escalated in some groups, with the maximum final dose ranging from 2.5 to 40.0 mg per day. Between 64% and 83% of the groups completed the total treatment period of 26 weeks without the need for rescue medication.
All doses reduced patients’ HbA1c levels significantly more than placebo, with the reductions versus placebo ranging from 0.4% for the 2.5 mg dose to 1.6% for the 40.0 mg dose, the latter of which was identical to the reduction achieved with weekly injectable semaglutide 1 mg.
At least 80% of patients taking an oral semaglutide dose of 5 mg or higher or injectable semaglutide achieved HbA1c levels below 7.0%, compared with less than 30% of those taking placebo. Patients taking injectable semaglutide or the higher oral doses also achieved significant reductions in bodyweight compared with placebo-treated patients.
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