Improved glycaemic control and weight benefit with iGlarLixi versus insulin glargine 100 U/mL in Chinese people with type 2 diabetes advancing their therapy from basal insulin plus oral antihyperglycaemic drugs: Results from the LixiLan-L-CN randomized controlled trial

Abstract

Aims: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs.

Materials and methods: LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30.

Results: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2 , corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: -0.7 (95% confidence interval: -0.9, -0.6)%; p < .0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p < .0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: -0.9 (95% confidence interval: -1.4, -0.5) kg; p = .0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar.

Conclusions: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.

Keywords: GLP-1 analogue; basal insulin; clinical trial; glycaemic control; iGlarLixi; type 2 diabetes.

Conflict of interest statement

XY, XG, JZ, XD, YL and WP declare that they have no competing interests; SG, LP, GN, EN and ES are employees of Sanofi and may hold shares and/or stock options in the company.

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

Figures

FIGURE 1

Response to therapy (mITT population). A, Mean HbA1c over time; B, change in HbA1c from baseline to Week 30; C, HbA1c target achievement and composite target achievement; D, pre‐ and postprandial plasma glucose; E, 7‐point SMPG profiles at baseline and Week 30 for iGlar; F, 7‐point SMPG profiles at baseline and Week 30 for iGlarLixi; G, change in body weight over time; and H, total insulin dose over time (mITT population). *p < .0001; †−15 ± 1 mmol/mol; ‡−8 ± 1 mmol/mol; §−8 (−10, −7) mmol/mol; ¶<53 mmol/mol; ǁat Week 30; #during the 30‐week randomized treatment period; ††exploratory endpoint, not included in the hierarchical testing procedure; ‡‡<48 mmol/mol; §§p‐value for descriptive purposes only, endpoint not included in the hierarchical testing procedure. BL, baseline; CI, confidence interval; HbA1c, glycated haemoglobin; iGlar, insulin glargine 100 U/mL; iGlarLixi, a fixed‐ratio combination of insulin glargine 100 U/mL and lixisenatide; LOCF, last observation carried forward; LS, least squares; P‐BL, prior to baseline; SD, standard deviation; SE, standard error; SMPG, self‐monitored plasma glucose; U, units; W, week

FIGURE 2

Incidence and event rates of hypoglycaemia during the 30‐week randomized treatment period (safety population). iGlar, insulin glargine 100 U/mL; iGlarLixi, a fixed‐ratio combination of insulin glargine 100 U/mL and lixisenatide; PY, participant‐years; PPY, per participant‐year