INDIRECT TREATMENT COMPARISON OF ORFORGLIPRON AND ORAL SEMAGLUTIDE IN JAPANESE PATIENTS WITH TYPE 2 DIABETES
Author(s)
Beatrice Osumili, MSc1, Masakazu Takeuchi, PhD2, Zhihong CAI, PhD2, Toshihiko Aranishi, PhD2, Katharina Ihle, MSc3, Jeremie Lebrec, PhD4, Tatjana Isailovic, MD, PhD5.
1Eli Lilly & Company, Bracknell, United Kingdom, 2Eli Lilly Japan K.K., Kobe, Japan, 3Lilly Deutschland GmbH, Bad Homburg, Germany, 4HaaPACS GmbH, Schriesheim, Germany, 5Eli Lilly and Company, Indianapolis, IN, USA.
1Eli Lilly & Company, Bracknell, United Kingdom, 2Eli Lilly Japan K.K., Kobe, Japan, 3Lilly Deutschland GmbH, Bad Homburg, Germany, 4HaaPACS GmbH, Schriesheim, Germany, 5Eli Lilly and Company, Indianapolis, IN, USA.
OBJECTIVES: Orforglipron, a once-daily (QD) oral, small-molecule, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1RA) in development for type 2 diabetes (T2D), was compared with oral semaglutide, a QD GLP-1RA approved in Japan for T2D, via indirect treatment comparison (ITC).
METHODS: A systematic literature review was conducted to identify randomized controlled trials of the orforglipron 3.0 mg QD investigational capsule formulation (prespecified expected maintenance dose; equivalent to the orforglipron 2.5 mg QD tablet formulation) and oral semaglutide 7.0 mg QD (maintenance dose) in Japanese adults with T2D receiving no antihyperglycemic background therapy. Eligible studies were compared using the Bucher ITC method. Efficacy estimand results were mandatory. Study endpoints included change from baseline to week 24 or 26 in mean HbA1c and body weight (BW). Sensitivity analyses adjusted for baseline differences in HbA1c and BW, using matching-adjusted ITCs (MAICs).
RESULTS: Two phase 3 studies were eligible for comparison, anchored via their respective placebo arms: the Japanese subpopulation of ACHIEVE-1 (ACHIEVE-1-JPN; orforglipron 3.0 mg QD [n=26] vs placebo [n=25] in patients with T2D), and PIONEER-9 (oral semaglutide 7.0 mg QD [n=49] vs placebo [n=49] in Japanese patients with T2D). Orforglipron and oral semaglutide achieved significant reductions versus placebo between baseline and week 24 (ACHIEVE-1-JPN) or 26 (PIONEER-9) for mean HbA1c, and significantly greater and comparable reductions versus placebo, respectively, for mean BW. ITCs showed statistically greater reductions with orforglipron versus oral semaglutide in HbA1c (mean difference -0.74%, 95% CI -1.21% to -0.27%) and BW (mean difference -2.70 kg, 95% CI -4.26 to -1.14). MAIC sensitivity analyses aligned with base-case findings.
CONCLUSIONS: ITC favored orforglipron 3.0 mg QD (capsule formulation; equivalent to orforglipron 2.5 mg QD tablet formulation) over oral semaglutide 7.0 mg QD in Japanese patients with T2D in terms of HbA1c and BW reduction. These findings are hypothesis-generating given the small sample sizes.
METHODS: A systematic literature review was conducted to identify randomized controlled trials of the orforglipron 3.0 mg QD investigational capsule formulation (prespecified expected maintenance dose; equivalent to the orforglipron 2.5 mg QD tablet formulation) and oral semaglutide 7.0 mg QD (maintenance dose) in Japanese adults with T2D receiving no antihyperglycemic background therapy. Eligible studies were compared using the Bucher ITC method. Efficacy estimand results were mandatory. Study endpoints included change from baseline to week 24 or 26 in mean HbA1c and body weight (BW). Sensitivity analyses adjusted for baseline differences in HbA1c and BW, using matching-adjusted ITCs (MAICs).
RESULTS: Two phase 3 studies were eligible for comparison, anchored via their respective placebo arms: the Japanese subpopulation of ACHIEVE-1 (ACHIEVE-1-JPN; orforglipron 3.0 mg QD [n=26] vs placebo [n=25] in patients with T2D), and PIONEER-9 (oral semaglutide 7.0 mg QD [n=49] vs placebo [n=49] in Japanese patients with T2D). Orforglipron and oral semaglutide achieved significant reductions versus placebo between baseline and week 24 (ACHIEVE-1-JPN) or 26 (PIONEER-9) for mean HbA1c, and significantly greater and comparable reductions versus placebo, respectively, for mean BW. ITCs showed statistically greater reductions with orforglipron versus oral semaglutide in HbA1c (mean difference -0.74%, 95% CI -1.21% to -0.27%) and BW (mean difference -2.70 kg, 95% CI -4.26 to -1.14). MAIC sensitivity analyses aligned with base-case findings.
CONCLUSIONS: ITC favored orforglipron 3.0 mg QD (capsule formulation; equivalent to orforglipron 2.5 mg QD tablet formulation) over oral semaglutide 7.0 mg QD in Japanese patients with T2D in terms of HbA1c and BW reduction. These findings are hypothesis-generating given the small sample sizes.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO193
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)