Differences in imeglimin response in subgroups of patients with type 2 diabetes stratified by data-driven cluster analysis: A post-hoc analysis of imeglimin clinical trial data.

Aim: To explore differences in imeglimin response among type 2 diabetes (T2D) patient clusters using data-driven cluster analysis.

Methods: Data-driven cluster analysis (non-hierarchical k-means clustering) was performed on randomized, double-blind, imeglimin monotherapy and adjunctive (to insulin) therapy trials based on four baseline variables: (1) disease duration; (2) body mass index (BMI); (3) HbA1c; and (4a) homeostatic model assessment of β-cell function (HOMA-β) (monotherapy trials) or (4b) insulin total daily dose (adjunctive trial).

Results: Four clusters were identified with distinct clinical characteristics in both monotherapy (1-4) and adjunctive therapy (I-IV) trials; clusters 1 and I had lower values across all four indices versus the overall population, clusters 2 and II had a longer diabetes duration, cluster 3 had higher baseline BMI and HOMA-β, and cluster III had higher baseline BMI and insulin total daily dose, while clusters 4 and IV had higher baseline HbA1c. Between-group differences in HbA1c change (95% confidence interval) and effect size (ES) at week 24 varied considerably by cluster (cluster 1: -0.82 [-1.00, -0.63], ES = 1.47; cluster 2: -0.64 [-0.89, -0.39], ES = 1.18; cluster 3: -0.86 [-1.38, -0.33], ES = 0.84; cluster 4: -1.27 [-1.73, -0.82], ES = 1.44). For imeglimin adjunctive therapy, HbA1c improvements were significant versus placebo at week 16, excluding cluster III (cluster I: -0.63 [-0.95, -0.31], ES = 0.88; cluster II: -0.66 [-1.02, -0.30], ES = 1.13; cluster III: -0.31 [-0.73, 0.11], ES = 0.46; cluster IV: -0.82 [-1.29, -0.35], ES = 0.99).

Conclusions: Differences in imeglimin response were observed among T2D patient clusters. Patient stratification may help with selection of those most probable to respond to imeglimin.