Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A subgroup analysis by baseline variables in the PIONEER 9 and PIONEER 10 trials

Abstract

Aims/Introduction To assess the impact of baseline characteristics on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. Materials and Methods In the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 9 and 10 trials, Japanese patients were randomized to once‐daily oral semaglutide (3, 7, or 14 mg) or a comparator (placebo or once‐daily subcutaneous liraglutide 0.9 mg in PIONEER 9; once‐weekly subcutaneous dulaglutide 0.75 mg in PIONEER 10) for 52 weeks, with 5 weeks of follow up. An exploratory analysis grouped patients in each trial according to baseline glycated hemoglobin (HbA1c; ≤8.0, >8.0–≤9.0, or >9.0%), body mass index (<25, ≥25–<30, or ≥30 kg/m2) and, for PIONEER 10 only, by background medication (sulfonylurea, glinide, thiazolidinedione, α‐glucosidase inhibitor, sodium‐glucose cotransporter 2 inhibitor). Efficacy (changes from baseline to week 26 in HbA1c and bodyweight) and safety were assessed. Results Seven hundred and one patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). In both trials, HbA1c reductions increased as baseline HbA1c increased; there were no other apparent patterns between the variables investigated and HbA1c or bodyweight changes. There was one statistically significant subgroup interaction between baseline HbA1c and estimated treatment differences in bodyweight change for oral semaglutide 14 mg versus placebo in PIONEER 9 (P = 0.0286). Baseline HbA1c, baseline body mass index and background medication did not appear to affect the proportions of patients reporting adverse events. Conclusions Oral semaglutide is effective across a range of baseline subgroups of Japanese patients with type 2 diabetes, with no unexpected safety findings.

Safety and efficacy analyses across age and body mass index subgroups in East Asian participants with type 2 diabetes in the phase 3 tirzepatide studies (SURPASS programme)

“…Lower doses of tirzepatide may be more appropriate for patients with lower baseline BMI or those concerned about weight loss.Baseline BMI and age did not have a clear relationship with the rate of TEAEs or SAEs. These results are comparable with similar subgroup analyses with GLP-1 RA therapies 37,38. Still, discontinuations because of AEs were highest in the BMI less than 25 kg/m 2 and age 65 years or older subgroup.…”

Updates of incretin‐related drugs for the treatment of type 2 diabetes

“…The reduction of HbA1c in these two trials was greater than those in other PIONEER trials in which most of the participants were white. A subgroup analysis of these two trails also elucidated that higher baseline HbA1c (≤8.0, >8.0-≤9.0 or >9.0%) related to higher HbA1c reduction, whereas BMI (<25, ≥25-<30 or ≥30 kg/ m 2 ) and background medication showed no interaction 20 . For AEs, there was no apparent difference between subgroups.…”

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“…In the PIONEER 1 and 8 trials oral semaglutide was significantly more beneficial compared to placebo and reduced baseline HbA1c in a dose-dependent way with 0.7 -1.4% and 0.5 -1.2%, respectively [6,76]. Oral semaglutide was more efficient than the active comparators in individuals with established type 2 DM (mean duration between 7.4 and 8.6 years) who were using other oral antidiabetics (PIONEER 2-4) [56,57,61,63].…”

“…The Peptide Innovation for Early Diabetes Treatment program or PIONEEER program was designed to evaluate the efficacy and safety of this formulation in a large and diverse group of patients with DM from early to late disease stage [12,59]. This phase 3 clinical research program comprised 8 10 international studies (PIONEER 1-10) [6,10,42,55,[61][62][63][76][77][78][79]. In these trials, oral semaglutide in three different doses of 3, 7 and 14 mg were examined in comparison to placebo (PIONEER 1, 8, and 4 -6), sitagliptin in dose of 100 mg (PIONEER 3 and 7), empagliflozin in dose of 25 mg (PIONEER 2), liraglutide (PIONEER 4, 9) and dulaglutide (PIONEER 10) [3,68,69] (Table II).…”