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.
Holler et al. (2025) studied this question.