Aims 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.

Materials and Methods We use mathematical modeling 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.

Results 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 prescribed doses yields nearly 70% of the weight loss of perfect adherence. Furthermore, such nonadherence causes only small fluctuations in body weight, assuming that patient do not typically miss more than several consecutive doses.

Conclusion 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.

The authors have declared no competing interest.

SDL and AC were supported by the National Science Foundation (Grant Nos. CAREER DMS-1944574 and DMS-2325258).

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The study used ONLY openly available human data that were originally located at https://doi.org/10.1056/NEJMoa2206038 and https://doi.org/10.1056/NEJMoa2032183.

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