Microdosing, fractional and split dosing of injectable GLP-1-based drugs: balancing potential benefits and risks.

Authors

Marco Infante, Giuseppe Seminara, Andrea Fabbri, Antonio Aversa

Published in

Minerva endocrinology. Nov 13, 2026. Epub Nov 13, 2026.

Abstract

Glucagon-like peptide-1 (GLP-1)-based drugs (also known as incretin receptor agonists) have revolutionized the management of type 2 diabetes and overweight/obesity. Microdosing, fractional dosing and split dosing of GLP-1-based drugs administered by subcutaneous injection (particularly the newer incretin receptor agonists semaglutide and tirzepatide) have recently emerged as alternative off-label dosing strategies used to improve long-term treatment tolerability while preserving or optimizing the therapeutic benefits of these agents. Evidence regarding these practices is mostly anecdotal and their use is not supported by manufacturers, scientific societies, drug regulatory agencies and official clinical guidelines. Fractional dosing of injectable incretin receptor agonists is the off-label administration of injectable GLP-1-based drugs at a fraction of a given standard approved drug dose by counting the audible and tactile clicks generated as the dose selector dial of pre-filled multi-dose injection pens (MDPs) is turned forward (off-label "click-counting" method). Microdosing of injectable incretin receptor agonists represents a form of fractional dosing that consists of administering subtherapeutic doses ["microdoses": doses lower than the lowest standard approved drug dose (starting dose)] of injectable GLP-1-based drugs with pre-filled MDPs through the "click-counting" method. Split dosing of injectable once-weekly incretin receptor agonists consists of administering smaller doses of an injectable once-weekly GLP-1-based drug more frequently than once per week with pre-filled MDPs through the "click-counting" method. This Special Article aims to provide a critical appraisal of the potential benefits and risks of microdosing, fractional dosing and split dosing of injectable GLP-1-based drugs, which warrant thorough investigation in future pharmacokinetic/pharmacodynamic studies and clinical trials.

PMID:
43021748
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.