Adaptive maintenance after incretin-induced weight loss: Moving beyond the continue-or-stop paradigm

Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have transformed obesity treatment, but weight regain after dose reduction or discontinuation remains a major clinical challenge. Post-treatment regain may reflect the re-emergence of biological pressures favouring weight restoration rather than treatment failure.

This was a narrative perspective examining evidence from randomized withdrawal and maintenance trials of incretin-based obesity medications and emerging pharmacological, behavioral, and monitoring strategies for long-term weight-loss maintenance. Relevant literature was identified through targeted PubMed searches and reference-list screening. Based on these data, we propose a conceptual framework of adaptive maintenance after incretin-induced weight loss.

Among pharmacological strategies following incretin-induced weight loss, continued obesity medication currently has the strongest direct evidence for limiting weight regain, although maintenance requirements vary substantially between individuals and some patients may maintain clinically meaningful weight reduction without continued medication. Potential strategies include continued obesity medication, monitored dose reduction with predefined re-escalation criteria, oral switching, reduced-frequency dosing, intermittent rescue therapy, and structured lifestyle support. Early changes in appetite, satiety, food preoccupation, weight trajectory, waist circumference, and cardiometabolic markers may help identify emerging relapse before substantial weight regain occurs, although these approaches require prospective validation.

Post-incretin weight-loss care should move beyond a binary choice between indefinite maximum-dose obesity medication and treatment discontinuation. Adaptive maintenance should aim to identify the minimum effective maintenance intensity that preserves clinically meaningful health benefit while accounting for relapse risk, treatment burden, and patient preferences.