The IDEAL (Insulin therapy DE-intensificAtion with iglarLixi) Randomised Controlled Trial-Study Design and Protocol

Abstract

Introduction: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua^®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide.

Methods: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor.

Planned outcomes: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated.

Trial registration: ClinicalTrials.gov, identifier NCT04945070.

Keywords: Complex insulin therapy simplification; Fixed-ratio combination of GLP-1 receptor agonist and basal insulin (FRC); Insulin glargine/lixisenatide (iGlarLixi); Insulin therapy de-intensification; Intensified insulin therapy (IIT); Multiple daily injections insulin regimen (MDI); Type 2 diabetes (T2D).