Efficacy of iGlarLixi on 5-year risk of diabetes-related complications: A simulation study

Abstract

Objective: This study simulated the 5-year risk of diabetes complications associated with the use of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, in type 2 diabetes (T2D) using the BRAVO diabetes model.

Methods: The six-month efficacy data of iGlarLixi and Standard of Care (SOC) were extracted from the LixiLan-O (NCT02058147) and ORIGIN (NCT00069784) trials, respectively. The trial participants' baseline characteristics were standardized to the ACCORD trial through a matching method. The BRAVO diabetes simulation model was used to project the 5-year complications based on T2D people baseline characteristics and treatment efficacy. An optimistic scenario where the six-month relative efficacy of iGlarLixi (i.e., iGlarlixi-SOC) lasted for 5 years, and a conservative scenario where the relative effect of iGlarLixi waned to none within 5 years were simulated.

Results: iGlarLixi compared with SOC was found to reduce HbA1c (-1.4%), SBP (-3.4 mm Hg), and BMI (-0.6 kg/m²) in six months. We simulated a 5-year risk reduction in major adverse cardiovascular events (MACE) (relative risk [RR] 0.77, 95% CI: 0.67-0.88), and all-cause mortality (RR 0.94, 95% CI: 0.92-0.96) under an optimistic scenario, and MACE (RR 0.86, 95% CI: 0.75-0.96), and all-cause mortality (RR 0.96, 95% CI: 0.92-0.98) under a conservative scenario.

Conclusions: The long-term use of iGlarLixi may lead to a substantial reduction in diabetes-related complications among people with T2D at elevated risk for CVD. The use of a simulation model to evaluate outcomes of treatment in a well-characterized patient cohort is novel. Such an approach may serve as a template for future evaluation of medications and combinations when the effect of a treatment is known, but a long-term outcome trial is not feasible.

Keywords: Diabetes complications; Efficacy; Simulation.