Modeling the Effect of Subcutaneous Lixisenatide on Glucoregulatory Endocrine Secretions and Gastric Emptying in Type 2 Diabetes to Simulate the Effect of iGlarLixi Administration Timing on Blood Sugar Profiles.

BACKGROUND: As type 2 diabetes (T2D) progresses, intensification to combination therapies, such as iGlarLixi (a fixed-ratio GLP-1 RA and basal insulin combination), may be required. Here a simulation study was used to assess the effect of iGlarLixi administration timing (am vs pm) on blood sugar profiles. METHODS: Models of lixisenatide were built with a selection procedure, optimizing measurement fits and model complexity, and were included in a pre-existing T2D simulation platform containing glargine models. With the resulting tool, a simulated trial was conducted with 100 in-silico participants with T2D. Individuals were given iGLarLixi either before breakfast or before an evening meal for 2 weeks and daily glycemic profiles were analyzed. In the model, breakfast was considered the largest meal of the day. RESULTS: A similar percentage of time within 24 hours was spent with blood sugar levels between 70 to 180 mg/dL when iGlarLixi was administered pre-breakfast or pre-evening meal (73% vs 71%, respectively). Overall percent of time with blood glucose levels above 180 mg/dL within a 24-hour period was similar when iGlarLixi was administered pre-breakfast or pre-evening meal (26% vs 28%, respectively). Rates of hypoglycemia were low in both regimens, with a blood glucose concentration of below 70 mg/dL only observed for 1% of the 24-hour time period for either timing of administration. CONCLUSIONS: Good efficacy was observed when iGlarlixi was administered pre-breakfast; however, administration of iGlarlixi pre-evening meal was also deemed to be effective, even though in the model the size of the evening meal was smaller than that of the breakfast.