Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ss-cell function in people with type 2 diabetes

Aim: Multiple studies support the efficacy of combining a glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed-ratio combinations of basal insulin + GLP-1RA represent a further advance to facilitate management. We assessed the impact of fixed-ratio combination basal insulin + GLP-1RA treatment on beta-cell function. Materials and Methods: We analysed data from 351 participants in the LixiLan-G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP-1RA, both on top of metformin. Participants received a 2-h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C-peptide determinations. beta-cell function parameters were resolved using mathematical modelling. Results: In the GLP-1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/beta-cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP-1RA group (p < .0001) despite an increase in body weight (+1.7 +/- 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP-1RA), while beta-cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP-1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP-1RA (p < .0001). Conclusions: In people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in beta-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.