The glucagon-like peptide 1 (GLP-1)-based diabetes and obesity drug semaglutide with the trade names Ozempic™ and Wegovy™, respectively, which is produced by Novo Nordisk, will become the second best-selling drug in 2024 with estimated worldwide Ozempic™ sales of US ~$16 billion. 1 Finally, the pharmacological treatment of obesity seems to have a breakthrough after decades of setbacks as previous weight loss medications had to be withdrawn from the market because of serious side effects, eg, the cannbinoid-1 receptor antagonist rimonabant due to significant psychiatric adverse events, the selective serotonin-norepinephrine reuptake inhibitor sibutramine due to an increased incidence of nonfatal heart attacks and strokes, and serotonin receptor agonists fenfluramine and dexfenfluramine due to heart valve damage. Due to the increased demand and off-label use of semaglutide, governments have issued shortage alerts with appropriate supply not expected to return to normal until at least the end of 2024. 2 The explosive increase in prescriptions of GLP-1-based medications has raised hopes and concerns across the psychiatric community because weight loss, weight gain, and obesity often go along with psychiatric disorders, and they can be a consequence of psychiatric therapies. This editorial will briefly summarize the rise of GLP-1 agonists and the major hopes and concerns associated with this new class of medications.
HOW GLP-1 RECEPTOR AGONISTS WORKGLP-1 is an intestinal peptide hormone that derives from posttranslational processing of proglucagon. GLP-1 is released in response to food intake and rapidly inactivated by the enzyme dipeptidyl peptidase IV (DPP-IV). GLP-1's actions may be transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. 3 GLP-1 stimulates insulin secretion but inhibits glucagon release, gastrointestinal motility, gastric emptying, appetite, and food intake. 3,4 As GLP-1 signaling boosts insulin secretion, GLP-1 receptor agonists have been tested for the treatment of type 2 diabetes (T2D). In April 2005, the first GLP-1 receptor agonist exenatide (also called exendin-4) was approved by the US Food and Drug Administration (FDA) for T2D. 5 Since then, the GLP-1 receptor agonists dulaglutide, liraglutide, lixisenatide, and semaglutide received FDA approval for T2D.When testing GLP-1 receptor agonists as T2D medication, it was observed that they also lead to weight loss, and thus, 2 of these GLP-1 receptor agonists, liraglutide and semaglutide, have been tested and approved for the treatment of obesity. Whereas liraglutide, which is metabolized by DPP-IVand neutral endopeptidase, required daily injections, semaglutide only needs to be injected once weekly. 6 Semaglutide became so popular that it caused a social media frenzy in 2022. It was reported in the press that celebrities used it as "skinny jab," which resulted in a global shortage of the drug, which is still ongoing. Meanwhile, semaglutide is even available as an oral tablet, 7 which boosted its popularity e...