A study has demonstrated that the higher doses of oral semaglutide (25 mg and 50 mg) were more effective than the approved 14 mg dose in reducing HbA1c and bodyweight in adults with inadequately controlled type 2 diabetes.
The safety profile of the higher doses did not raise any new concerns. This trial is registered with ClinicalTrials.gov, NCT04707469, and the European Clinical Trials register, EudraCT 2020-000299-39, and is complete.
The phase 3b clinical trial published in the Lancet on June 25th aimed to investigate the efficacy of a new formulation of oral semaglutide at higher doses compared to the approved 14 mg dose in adults with inadequately controlled type 2 diabetes. The trial was conducted globally at 177 sites across 14 countries.
The trial enrolled adults with type 2 diabetes who had a glycated hemoglobin (HbA1c) level between 8.0% and 10.5%, a body mass index (BMI) of 25.0 kg/m2 or greater, and were receiving stable daily doses of one to three oral glucose-lowering drugs. The participants were randomly assigned to receive once-daily oral semaglutide at doses of 14 mg, 25 mg, or 50 mg for 68 weeks.
The trial followed a double-blind design, meaning that both the participants and the investigators were unaware of the assigned dose throughout the trial.
The primary endpoint of the trial was the change in HbA1c from baseline to week 52, and this was evaluated using a treatment policy estimand in the intention-to-treat population. Safety assessments were also conducted in all participants who received at least one dose of the trial drug.
Between January 15 and September 29, 2021, a total of 1,606 participants (58.3% male, 41.7% female) were included in the study. The baseline HbA1c was 9.0%, and the mean bodyweight was 96.4 kg. The results showed that both the 25 mg and 50 mg doses of oral semaglutide were superior to the 14 mg dose in reducing HbA1c and bodyweight in adults with inadequately controlled type 2 diabetes.
The mean changes in HbA1c at week 52 were -1.5 percentage points for 14 mg, -1.8 percentage points for 25 mg, and -2.0 percentage points for 50 mg.
Adverse events were reported by a majority of participants in all three dose groups, with gastrointestinal disorders occurring more frequently in the 25 mg and 50 mg groups. However, most of these events were mild to moderate in severity. Ten deaths occurred during the trial, but none of them were considered to be related to the treatment.