Considerations and challenges in microdosing of GLP-1-based receptor agonists

INTRODUCTION: This commentary summarizes the pharmacologic rationale, emerging evidence, clinical considerations, and limitations of microdosing glucagon-like peptide-1 (GLP-1)-based therapies. Microdosing of single or dual GLP-1 receptor agonists (RAs) has emerged as an off-label strategy to improve tolerability, reduce cost, and expand access during periods of medication shortages. Although standard doses of GLP-1-based RAs demonstrate robust efficacy for weight loss and glycemic control, many individuals experience dose-dependent gastrointestinal adverse effects or face financial and accessibility barriers. Because high-quality evidence is essentially absent, this commentary summarizes the pharmacologic rationale, real-world reports, clinical considerations, and limitations of microdosing. AREAS COVERED: Microdosing - typically defined as the use of 25-50% of manufacturer-recommended starting doses or extended dosing intervals - has gained traction during recent shortages through patient communities, telemedicine-based weight loss programs, and clinician anecdotes. Techniques include 'click counting' with multidose pens or extended-interval dosing. EXPERT OPINION: Early reports suggest potential benefits, including reduced nausea, improved adherence, and modest weight loss; however, high-quality clinical evidence remains limited, and safety concerns persist regarding compounded products, nonstandard dose measurement, and dosing accuracy.