Characteristics and Glycemic Outcomes of T2D Patients Titrated to 60 U/day iGlarLixi vs Insulin in the LixiLan-L Trial

Authors: Lawrence Blonde1, Timothy S. Bailey2, Jason Chao3, Terry Dex4, Juan Pablo Frias5, Luigi Meneghini6, Michelle Roberts4, Vanita R. Aroda7. 

Affiliations: 1Ochsner Medical Center in New Orleans, Louisiana; 2AMCR Institute, Escondido, CA, USA; 3 Xinyi, Inc. Bridgewater, NJ, USA; 4Sanofi, Bridgewater, NJ,USA; 5National Research Institute, Los Angeles, CA; 6University of Texas Southwestern Medical Center and Parkland Health & Hospital System, Dallas, TX, USA; 7MedStar Health Research Institute, Hyattsville, MD, USA.

Abstract
BACKGROUND: iGlarLixi is a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide (LIXI), with a maximum daily dosage of 60 U iGlar/20 µg LIXI. 
AIM: This post hoc analysis of data from the LixiLan-L trial (EFC12405) explored the characteristics and outcomes in patients on 60 U/day of iGlarLixi or iGlar at study end compared to those on <60 U/day.
METHODS: In LixiLan-L, patients with T2D uncontrolled on basal insulin ± OADs were randomized to iGlarLixi (n=366) or iGlar (n=365) for 30 weeks, after 6 weeks of iGlar optimization.  Data were analyzed descriptively (number [N], mean, and standard deviation [SD]) by treatment group. Tipping point analyses were used to compare variable relationships and potential effect of dose capping at 60 U.
RESULTS: In the iGlarLixi and iGlar arms, 27.0% and 30.7% of patients, respectively, reached 60 U at 30 weeks. More patients on iGlarLixi achieved A1C <7.0% (60 U: 43%; <60 U: 66%) vs iGlar (60 U: 24%; <60 U: 34%). In both arms, patients on 60 U were younger, had higher baseline weight, BMI, FPG, and insulin dose vs patients using <60 U (Table). Exploratory tipping point analysis showed higher baseline BMI (iGlarLixi: > 42 kg/m2, iGlar: > 45 kg/m2), weight (iGlarLixi:  ≥ 125 kg, iGlar:  ≥ 140 kg), and insulin dose (iGlarLixi ≥0.78 U/kg, iGlar ≥0.70 U/kg) were associated with greater likelihood of reaching 60 U. Regardless of final dose, iGlarLixi patients had numerically greater mean A1C reduction ( <60 U -1.2%, 60U −1.0%) vs. iGlar ( <60 U -0.6%, 60 U −0.5%) and greater PPG reductions from baseline. 60 U users in both arms had lower symptomatic hypoglycemia, but similar FPG and PPG changes from baseline vs patients using <60 U. Of patients receiving 60 U, 5.1% in the iGlarLixi and 10.7% in the iGlar arm required rescue therapy. Patients reaching 60 U but not at A1C goal who required protocol-specified rescue therapy were generally younger with lower baseline FPG than those not requiring rescue therapy; however, all other baseline characteristics were similar.
CONCLUSION: Despite similar weight-adjusted insulin doses in both arms, A1C reduction and % of patients achieving glycemic goal was greater with iGlarLixi vs iGlar at 60 U. Characteristics of 60 U users may inform clinical decisions.

Characteristics and glycemic outcomes of T2D patients titrated to 60 U/day iGlarLixi vs insulin in the LixiLan-L trial