Incretin mimetics for weight loss forgive nonadherence

May 14, 2025Diabetes, obesity & metabolism

Weight loss drugs that mimic gut hormones still work despite missed doses

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Taking 80% of prescribed doses of semaglutide or tirzepatide results in around 90% of the weight loss achieved with perfect adherence.

Semaglutide and tirzepatide maintain strong weight loss efficacy despite missed doses.
Missing 50% of prescribed doses still results in nearly 70% of the weight loss associated with full adherence.
Nonadherence leads to only small fluctuations in body weight when patients miss a few consecutive doses.
The belief that significant weight loss necessitates at least 80% adherence may need to be reconsidered.

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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 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.

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 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.

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.

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Incretin mimetics for weight loss forgive nonadherence

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