Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Dec 10;17(12):1596.
doi: 10.3390/pharmaceutics17121596.

Oral Treatment of Obesity by GLP-1 and Its Analogs

Natasa Holler  1 , Ivana Ruseska  1 , Anna-Laurence Schachner-Nedherer  1 , Andreas Zimmer  1 , Christina Petschacher  1
Affiliations
Review

Oral Treatment of Obesity by GLP-1 and Its Analogs

Natasa Holler et al. Pharmaceutics. .

Abstract

Obesity is a multifaceted disease that significantly increases the risk of various chronic conditions. GLP-1R (co)-agonists first emerged as therapeutics for treatment of type 2 diabetes mellitus and have since become an established drug class for improving glycemic control. The interest in GLP-1 for obesity treatment has surged in 2015 after the approval of Saxenda® (liraglutide). To date, GLP-1 analogs are primarily administered by s.c. injection, which poses a significant burden on patient compliance. To address this challenge, research has focused on oral delivery. This review provides a concise overview of the techniques explored to enhance the oral delivery of GLP-1 analogs for the treatment of obesity. Relevant strategies include the following: (1) the use of permeation enhancers to increase gastrointestinal absorption of peptides; (2) micro- and nanocarriers loaded with GLP-1, including targeted delivery systems and general techniques for active drug targeting; (3) GLP-1 gene delivery; and (4) advanced microbiome systems for GLP-1 delivery. The potential for misuse and side-effects of GLP-1 analogs are also discussed.

Keywords: GLP-1 abuse; gene delivery; glucagon-like peptide 1; microbiome engineering; microbiome therapeutics; nanocarriers; nanoparticles; oral peptide delivery; peptide therapeutics; targeted delivery.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Systemic effects of GLP-1. Created in BioRender. Holler, N. (2025). https://BioRender.com/5ozl7s0.
Figure 2
Figure 2
Processing of the preproglucagon gene to GLP-1. Created in BioRender.com. Holler, N. (2025). https://BioRender.com/zmznx0i. Layout adapted from Lafferty et al., 2021 [78], licensed under CC BY 4.0.
Figure 3
Figure 3
Molecular structures of the FDA-approved GLP-1R agonists and co-agonists. Created with BioRender.com using an adapted template. Holler, N. (2025). https://BioRender.com/5n7ehcf. Layout inspired by Yu et al., 2018 [55].
See this image and copyright information in PMC

References

    1. WHO New WHO/Europe Fact Sheet Highlights Worrying Post-COVID Trends in Childhood Obesity. 2024. [(accessed on 20 November 2025)]. Available online: https://www.who.int/europe/news/item/29-11-2024-new-who-europe-fact-shee....
    1. Zhang X., Ha S., Lau H.C.H., Yu J. Excess body weight: Novel insights into its roles in obesity comorbidities. Semin. Cancer Biol. 2023;92:16–27. doi: 10.1016/j.semcancer.2023.03.008. - DOI - PubMed
    1. WHO One in Eight People Are Now Living with Obesity. Volume 45. 2024. [(accessed on 20 November 2025)]. Available online: https://www.who.int/news/item/01-03-2024-one-in-eight-people-are-now-liv....
    1. Novelli G., Cassadonte C., Sbraccia P., Biancolella M. Genetics: A Starting Point for the Prevention and the Treatment of Obesity. Nutrients. 2023;15:2782. doi: 10.3390/nu15122782. - DOI - PMC - PubMed
    1. McCafferty B.J., Hill J.O., Gunn A.J. Obesity: Scope, Lifestyle Interventions, and Medical Management. Tech. Vasc. Interv. Radiol. 2020;23:100653. doi: 10.1016/j.tvir.2020.100653. - DOI - PubMed

LinkOut - more resources