Glucagon-like peptide-1 receptor agonists: Evolution, gastrointestinal adverse effects, and future directions

Obesity is a global pandemic that has been threatening the worldwide population. It has been reported to be associated with an increase in the risk of chronic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and other diseases, including some malignancies. Currently, the first line of management includes lifestyle modifications. However, recently, bariatric surgeries were introduced to combat obesity. The previous modalities of management are always challenging since lifestyle could have limited long-term effectiveness and difficulty to achieve, and surgeries are invasive and also require a lifestyle modification and commitment. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were initially introduced as a rising star for managing T2DM, with patients benefiting from the control of blood sugar and weight loss. These medications work by enhancing feelings of fullness, slowing down digestion, and ultimately reducing calorie intake. However, GLP-1RAs are not without side effects and have some costs. Common side effects include gastrointestinal (GI) adverse events such as nausea, vomiting, diarrhea, and a lack of GI motility, which is the main mechanism through which the drug induces a feeling of fullness and promotes weight loss, potentially resulting in treatment discontinuation. More serious, though less frequent, risks include pancreatitis, gallbladder diseases, and, rarely, thyroid C-cell cancers. This review aimed to discuss the globally emerging role of GLP-1RAs in obesity management and highlight some safety considerations for patients taking these drugs.