Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials

Abstract

Aims: To evaluate, through exploratory post hoc subgroup analyses, the efficacy and safety of oral semaglutide versus comparators in Japanese patients enrolled in the global PIONEER 1, 3, 4 and 8 clinical trials.Materials and Methods: Patients were randomized to once-daily oral semaglutide 3, 7 or 14 mg or comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg).Change from baseline in glycated haemoglobin (HbA1c) and body weight, and proportions of patients attaining HbA1c <7.0% (53 mmol/mol) and body weight loss ≥5%, were analysed at week 26 for all Japanese patients in each trial separately using the treatment policy estimand (regardless of treatment discontinuation or rescue medication use). Adverse events (AEs) were analysed descriptively.Results: Reductions in HbA1c from baseline in Japanese patients were 1.0% to 1.2% (11.3 mmol/mol to 13.3 mmol/mol) and 1.4% to 1.7% (15.7 mmol/mol to 18.3 mmol/ mol) for oral semaglutide 7 mg and 14 mg, respectively. HbA1c reductions were similar or greater than with comparators. Body weight reductions were 1.0% to 2.7% and 3.7% to 4.7% for oral semaglutide 7 mg and 14 mg, respectively, and were generally greater with oral semaglutide than comparators. As expected, the main class of AEs was gastrointestinal, and these AEs comprised most commonly mild-to-moderate constipation, nausea and diarrhoea.Conclusions: Oral semaglutide appears efficacious and well tolerated in Japanese patients across the type 2 diabetes spectrum.

A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of danuglipron (PF‐06882961), an oral small‐molecule glucagon‐like peptide‐1 receptor agonist, in Japanese adults with type 2 diabetes mellitus

“…9 However, both the overall and gastrointestinal safety profiles of danuglipron are generally consistent with those described for peptidic GLP-1R agonists, 10,11 including the recent oral formulation of semaglutide. [12][13][14][15] In this study, increases in heart rate were observed in danuglipron dose groups after 8 weeks of dosing, which was observed in the previous study in Western participants 8 and in other studies with peptidic GLP-1R agonists. 16 The magnitude of heart-rate increases observed in this study is in line with short-term clinical data published with peptidic GLP-1R agonists.…”

“…More gradual dose‐escalation schemes over longer treatment durations are anticipated to result in lower incidence rates of gastrointestinal AEs 9 . However, both the overall and gastrointestinal safety profiles of danuglipron are generally consistent with those described for peptidic GLP‐1R agonists, 10,11 including the recent oral formulation of semaglutide 12‐15 …”

“… 9 However, both the overall and gastrointestinal safety profiles of danuglipron are generally consistent with those described for peptidic GLP‐1R agonists, 10 , 11 including the recent oral formulation of semaglutide. 12 , 13 , 14 , 15 …”

Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post‐hoc analysis

“…The greater treatment effects of semaglutide on HbA 1c and bodyweight could be due to differences in the pathophysiology of type 2 diabetes and genetic architecture in East Asian populations compared with those of Western populations 1 , 2 , 3 , 4 , 14 . For example, the presence of variants in diabetes‐associated loci that are unique to Japanese persons vs Europeans could be linked to differential effects on type 2 diabetes pathways between populations 15 .…”

“…The once‐daily oral formulation of semaglutide is also approved for type 2 diabetes treatment in Japan 19 , and the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes have been investigated in a post‐hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 clinical trials 14 . Similar to the results of our analysis of once‐weekly subcutaneous semaglutide, once‐daily oral semaglutide 3, 7 or 14 mg was found to be efficacious and well tolerated in Japanese participants 14 . Change from baseline to week 26 in HbA 1c was −1.0 to −1.2% points and −1.4 to −1.7%‐points for oral semaglutide 7 mg and 14 mg, respectively.…”