Impact of disease duration and β-cell reserve on the efficacy of switching to iGlarLixi in adults with type 2 diabetes on glucagon-like peptide-1 receptor agonist therapy: Exploratory analyses from the LixiLan-G trial

Aim: To evaluate the efficacy of iGlarLixi by C-peptide levels and duration of diabetes in an exploratory analysis of the LixiLan-G study. Methods: LixiLan-G was a 26-week, randomized, open-label study in adults with type diabetes (T2D) inadequately controlled while on a glucagon-like peptide-1 receptor agonist (GLP-1 RA), with metformin, with or without pioglitazone and/or a sodium-glucose co-transporter-2 inhibitor. This analysis investigated the efficacy of switching to iGlarLixi by fasting baseline quartile C-peptide levels and baseline quartile of duration of T2D compared with continued GLP-1 RA use. Results: Change in glycated hemoglobin (HbA1c) from baseline to week 26 was significantly greater with iGlarLixi compared with continued GLP-1 RAs across all fasting C-peptide quartiles (−1.00% to −1.06% vs. –0.23% to −0.54% range, respectively) and irrespective of all T2D duration quartiles (−0.94% to −1.07% vs. –0.25% to −0.50% range). A significantly greater proportion of participants in the iGlarLixi arm achieved an HbA1c of <7% across all C-peptide quartiles (51%-73% range) than in the GLP-1 RA arm (19%-32% range). The greatest reductions in HbA1c in participants receiving iGlarLixi were observed in those with the shortest duration of disease, although consistently greater than reductions observed with continued GLP-1 RAs. Reductions in HbA1c were comparable across C-peptide quartiles within the iGlarLixi arm. Conclusions: The results of this study suggest that iGlarLixi is an effective treatment option, irrespective of C-peptide levels or duration of diabetes, in adults with insufficiently controlled T2D receiving GLP-1 RAs.