Alternative dosing regimens of GLP-1 receptor agonists may reduce costs and maintain weight loss efficacy

Abstract

Aims: To discover alternative dosing regimens of incretin mimetics that simultaneously reduce costs and maintain weight loss efficacy. As a secondary objective, we used our results to explore how allocating a limited incretin mimetics budget could affect public health on a national scale. Materials and Methods: We used mathematical modeling and simulation of semaglutide and tirzepatide. For semaglutide, we used a recent pharmacokinetic (PK) and pharmacodynamic (PD) model. For tirzepatide, we used a recent PK model and modeled PD by reparameterizing the semaglutide PD model to fit tirzepatide clinical data. Results: Reducing dose frequency does not commensurately reduce weight loss. For example, merely switching from one dose per week (q1wk) to one dose every two weeks (q2wk) maintains roughly 75% of the weight loss. Furthermore, if the decrease in dose frequency involves an appropriate increase in dose size, then approximately 100% of the weight loss is maintained. In addition, we compared offering incretin mimetics to (1) a fraction of obese US adults with q1wk dosing versus (2) twice as many obese US adults with q2wk dosing. Though scenarios (1) and (2) require the same budget, our analysis suggests that (2) reduces national obesity and mortality to a much greater degree. Conclusion: Our study highlights the potential utility of alternative dosing regimens of incretin mimetics. Compared to standard once-weekly dosing, costs can be halved and weight loss maintained. These cost-saving results have implications for patients, physicians, insurers, and governments.