Objective: This post-hoc analysis was conducted to characterize the distribution of participant-level responses to imeglimin.
Methods: Pooled data from two monotherapy trials of imeglimin [Ph2b (PXL008-014) and Ph3 (PXL008-018)] and data from an imeglimin add-on to insulin trial [Ph3 (PXL008-020)] in Japanese adults with type 2 diabetes were included in the analysis. Multivariable analyses examined the effects of age, treatment history, baseline HbA1c, and baseline BMI on improvements in HbA1c in imeglimin and placebo groups. Response distributions were analyzed using finite mixture models, and the optimal number of components was selected using the Akaike and the Bayesian information criterion.
Results: In the monotherapy trial, the best-fitting model for the response distribution to imeglimin was a mixture of six normal distributions. The mean change in HbA1c from baseline to week 24 for each distribution and percentage of patients were as follows; -1.34 (22.4 %), -0.58 (60.4 %), +0.02 (12.1 %), +0.10 (3.93 %), +1.31 (<1 %), and +1.85 (1.12 %). Improvement in HbA1c with imeglimin monotherapy increased with higher baseline HbA1c, higher age, lower baseline BMI, and in treatment naïve patients. In the add-on to insulin therapy, the best-fitting model for the response distribution for imeglimin was a mixture of five normal distributions. The mean change in HbA1c from baseline to 16 weeks for each component and percentage of patients were as follows; -2.21 (3.2 %), -2.00 (1.85 %), -1.20 (9.25 %), -0.63 (81.2 %), +1.20 (4.50 %). Improvement in HbA1c with imeglimin add-on to insulin therapy increased with higher baseline HbA1c, higher age, and lower baseline BMI.
Conclusions: The distribution of responses to imeglimin was normally distributed and multimodal, suggesting that more than 80% of participants in the clinical trial showed substantial antidiabetic effect beyond the placebo effect.
K. Hagi: Employee; Sumitomo Dainippon Pharma Co., Ltd. K. Kochi: Employee; Sumitomo Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. H. Watada: Speaker's Bureau; Bayer Inc., Sanofi, Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Abbott Japan Co., Ltd., Eli Lilly and Company, Boehringer-Ingelheim, Daiichi Sankyo, Taiho Pharmaceutical Co. Ltd., Kowa Company, Ltd., Teijin Pharma Limited, Mitsubishi Tanabe Pharma Corporation. Research Support; Sumitomo Dainippon Pharma Co., Ltd., Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Abbott Japan Co., Ltd., Teijin Pharma Limited, Takeda Pharmaceutical Company Limited, Taiho Pharmaceutical Co. Ltd., Sanwa Kagaku, Souiken. K. Kaku: Speaker's Bureau; Astellas Pharma Inc., Kowa Company, Ltd. Advisory Panel; Novo Nordisk. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Taiho Pharmaceutical Co. Ltd. K. Ueki: Research Support; Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, Abbott Japan Co., Ltd., Daiichi Sankyo.
