Long-Acting Semaglutide Microspheres: A New Formulation That Could Mean Monthly Dosing | Research

The takeaway

Adding hydroxyethyl starch to semaglutide-loaded PLGA microspheres achieved 94% encapsulation, 83% controlled release over 44 days, and nearly three weeks of glycemic control in animal studies.

44-day release
Semaglutide microspheres with HES achieved controlled drug release over 44 days, compared to the current weekly injection schedule

What the researchers found

HES-containing PLGA microspheres achieved 94.38% semaglutide encapsulation, 83.23% controlled release over 44 days, prevented 30.65% drug loss versus HES-free microspheres, and provided ~3 weeks of glycemic control in vivo.

Why it matters

Weekly semaglutide injections are a barrier to patient adherence. A monthly injectable microsphere formulation would significantly reduce injection burden, potentially improving outcomes for millions of diabetes and obesity patients.

The numbers in context

HES addition to the W1 phase showed significant enhancement of semaglutide stability compared to formulations without the starch protectant.

How the study worked

Formulation study using W1/O/W2 double emulsion method to create PLGA microspheres. Tested hydroxyethyl starch addition at various concentrations. Characterized encapsulation efficiency, in vitro release kinetics, semaglutide structural integrity, and in vivo glycemic control.

Who was studied

In vitro PLGA microsphere formulations containing semaglutide

What this study cannot tell us

Primarily in vitro formulation work with limited in vivo data. Human pharmacokinetics, bioavailability, and injection-site tolerability are unknown. Scale-up manufacturing challenges for microspheres are not addressed. The ~3 weeks of glycemic control observed in animals may not translate directly to humans.

How to read the evidence

Preliminary evidence: well-characterized formulation study with encouraging in vitro results and limited in vivo data. No human clinical trial data yet.

When this study was published

Published in 2024. Reflects active research into next-generation semaglutide delivery systems.

The bigger picture

As GLP-1 drugs become the most important class of metabolic medications, extending their dosing intervals is a top pharmaceutical priority. This microsphere approach could apply not just to semaglutide but to other peptide drugs that currently require frequent injections, representing a platform technology for long-acting peptide delivery.

Questions still open

Can this microsphere formulation achieve once-monthly dosing in human clinical trials?
How does the injection-site experience compare to current weekly semaglutide injections?
Could this PLGA-HES platform be applied to other peptide drugs like tirzepatide or liraglutide?

Common questions

Could semaglutide become a monthly injection?

This microsphere technology achieved controlled semaglutide release over 44 days in lab tests and ~3 weeks of blood sugar control in animals. If clinical trials succeed, monthly or even less frequent semaglutide injections could become reality.

What are PLGA microspheres?

PLGA is a biodegradable polymer used in many approved medical products. Microspheres are tiny drug-loaded beads injected under the skin that slowly dissolve and release medication over weeks to months, eliminating the need for frequent injections.

Read the original research

Effect of hydroxyethyl starch on drug stability and release of semaglutide in PLGA microspheres.

International journal of pharmaceutics, 654, 123991

View on PubMed ↗Publisher’s paper ↗

Citation

Zeng, Han; Song, Jiaxin; Li, Yiyao; Guo, Chen; Zhang, Yu; Yin, Tian; He, Haibing; Gou, Jingxin; Tang, Xing. (2024). Effect of hydroxyethyl starch on drug stability and release of semaglutide in PLGA microspheres.. International journal of pharmaceutics, 654, 123991. https://doi.org/10.1016/j.ijpharm.2024.123991