Daisuke Yabe 1, Jiro Nakamura 2, Hideaki Kaneto 3, Srikanth Deenadayalan 4, Andrea Navarria 4, Mette Gislum 4, Nobuya Inagaki 5, PIONEER 10 Investigators
Main idea: Oral semaglutide was well tolerated in Japanese patients with type 2 diabetes. Once-daily oral semaglutide significantly reduced HbA1c (14 mg dose) and bodyweight (7 mg and 14 mg doses) versus weekly subcutaneous dulaglutide 0·75 mg by week 52.
Background: New glucose-lowering medications need to be investigated in east Asian populations, as the clinical characteristics of type 2 diabetes differ between western and east Asian patients. The PIONEER 10 study aimed to evaluate the safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes.
Methods: PIONEER 10 was an open-label, randomized, active-controlled, phase 3a trial done at 36 sites in Japan. Patients aged 20 years and older with uncontrolled type 2 diabetes were randomly assigned. The primary endpoint was the number of treatment-emergent adverse events over 57 weeks. This trial is registered with ClinicalTrials.gov, NCT03015220.
Findings: In this study, 492 patients were screened and 458 were randomly assigned to oral semaglutide. The most common adverse events were infections and gastrointestinal events. No deaths or severe hypoglycaemic events were reported. HbA1c reductions from baseline to week 52 were -0.9 percentage points with oral semgulutide 3 mg, -1.7 percentage points (0.1) with oralSemagluide 7 mg, and 1.0 kg with oral Semaglulide 14 mg, but -2.6 kg with dulaglutside. Gastrointestinal adverse events (mostly mild and transient constipation and nausea) occurred in a dose-dependent manner with oral semaglutide. No deaths or severe hypoglycemic events were reported.