Incretin mimetics for weight loss forgive nonadherence

GLP-1 and GIP-GLP-1 agonists have emerged as potent weight-loss medications. These incretin mimetics often have low patient adherence, and as with any medication, clinically meaningful efficacy requires adequate adherence. But what constitutes "adequate" adherence for incretin mimetics? The purpose of this paper is to address this question.

We use mathematical modelling and stochastic simulation to investigate the weight loss efficacy of incretin mimetics under imperfect adherence. We use validated pharmacokinetic and pharmacodynamic models of semaglutide and tirzepatide and assume that simulated patients randomly miss doses.

We find that semaglutide and tirzepatide forgive nonadherence, meaning that strong weight loss efficacy persists despite missed doses. For example, taking 80% of the prescribed doses yields around 90% of the weight loss achieved under perfect adherence. Taking only 50% of the prescribed doses yields nearly 70% of the weight loss of perfect adherence. Furthermore, such nonadherence causes only small fluctuations in body weight, assuming that patients do not typically miss more than several consecutive doses.

Incretin mimetics are powerful tools for combating obesity, perhaps even if patients can consistently take only half of their prescribed doses. The common assumption that significant weight loss requires at least 80% adherence needs revision.