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

Ele Ferrannini, Elisabeth Niemoeller, Terry Dex, Soraly Servera, Andrea Mari, Ele Ferrannini, Elisabeth Niemoeller, Terry Dex, Soraly Servera, Andrea Mari

Abstract

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 β-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. β-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/β-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 β-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 β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

Keywords: glucagon-like peptide 1 receptor agonist; iGlarLixi; insulin secretion; mixed-meal tolerance test; β-cell function.

Conflict of interest statement

EN, TD and SS are employees of, and have shares/stock options for Sanofi. EF is a member of Boehringer‐Ingelheim/Eli Lilly & Company and Lexicon advisory boards, has received speaker fees from Boehringer‐Ingelheim/Eli Lilly & Company and MSD, and research grant support from Janssen and Oramed, and does ad hoc consulting for AstraZeneca, Sanofi and Oramed. AM has received research grant support from Eli Lilly & Company.

© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Plasma glucose and C‐peptide curves at baseline and 26 weeks in the two treatment arms. Plots are mean ± standard error of the mean. GLP‐1RA, glucagon‐like peptide 1 receptor agonist
FIGURE 2
FIGURE 2
Insulin secretion‐plasma glucose dose‐response curves at baseline and 26 weeks in the iGlarLixi and GLP‐1RA arms. Plots are mean ± standard error of the mean. GLP‐1RA, glucagon‐like peptide 1 receptor agonist; iGlarLixi, insulin glargine 100 U/ml + lixisenatide
FIGURE 3
FIGURE 3
Multivariate logistic regression of the probability of an HbA1c

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Source: PubMed

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