PIONEER 9, 10 confirm oral semaglutide efficacy in Japanese population
medwireNews: Results of the PIONEER 9 and 10 trials show that oral semaglutide is efficacious in Japanese people with type 2 diabetes.
The results of both studies are published in The Lancet Diabetes & Endocrinology, along with a commentary from André Scheen (CHU Liège, Belgium), who notes the importance of testing diabetes medications in an exclusively East Asian population, “since the pathophysiology of type 2 diabetes is slightly different in Japanese individuals than in white patients as Japanese patients generally have a lower BMI and a greater defect in insulin secretion.”
PIONEER 9 was a phase 2/3a trial, testing once-daily oral semaglutide at doses of 3, 7, and 14 mg against oral placebo or open-label daily subcutaneous liraglutide 0.9 mg in 243 people with type 2 diabetes (average duration 7.6 years) that was poorly controlled with lifestyle measures or low-dose oral antidiabetic monotherapy, which was discontinued at baseline.
And PIONEER 10 was a phase 3a trial, testing the same semaglutide doses against weekly subcutaneous dulaglutide 0.75 mg as an add-on to existing oral antidiabetic monotherapy in 458 people with type 2 diabetes (average duration 9.4 years). Both trials ran for 52 weeks.
Glycated hemoglobin (HbA1c) levels decreased significantly in all active treatment groups of both trials. The average reductions versus placebo ranged from 1.3% to 1.9% (all significant) from a baseline of 8.2%, and there were no significant differences versus liraglutide.
Compared with dulaglutide, oral semaglutide was significantly more efficacious at a dose of 14 mg, giving an average 0.3% difference in HbA1c, had similar efficacy at 7 mg, and was significantly less efficacious at 3 mg.
Scheen points out that the apparently greater glucose-lowering efficacy seen here relative to the other PIONEER trials may be explained by use of liraglutide and dulaglutide at the maximal approved doses for the Japanese population, which are lower than used elsewhere (1.8 and 1.5 mg, respectively), while at the same time using oral semaglutide at a dose “similar to that proposed worldwide.”
He also notes that the adverse event profile differed somewhat to that reported in the other PIONEER trials. Gastrointestinal events were most common, as expected, but with constipation the most frequently reported complaint, rather than nausea, in 15% versus 9% of the semaglutide 14 mg group in PIONEER 10, for example.
In addition to its glucose-lowering effects, oral semaglutide at the 14 mg dose also significantly reduced bodyweight, by an average 1.8 kg versus placebo, by 3.2 kg versus liraglutide, and by 2.6 kg versus dulaglutide.
The research teams reporting PIONEER 9 and 10 were led by Yuichiro Yamada (Akita University Graduate School of Medicine, Japan) and Daisuke Yabe (Gifu University Graduate School of Medicine, Japan), respectively.
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