Ozempic, Wegovy, Mounjaro – ask anyone in 2025 if they’ve heard of these and they will most likely say yes. These drugs, all classified as glucagon-like peptide 1 (GLP-1) agonists, have recently exploded in popularity as weight-loss treatments. Ozempic has championed this market, with approximately 40 times more users in 2022 than in 2019. Similarly, during their first year on the market, Mounjaro and Wegovy had 254% and 84% increases in monthly usage, respectively. Google Trends show a four-fold increase in searches for GLP-1 agonists from 2018 to 2025, and social media pages are flooded with endorsements from celebrities who used these methods to shed a few pounds. The drugs even got a highlight during SuperBowl LIX via an ad from the telehealth company Hims & Hers. This near-constant exposure begs the question: what exactly are GLP-1 agonists and how do they work?

GLP-1 in the body

Interestingly enough, these drugs were originally created to treat type 2 diabetes. Because they are classified as “agonists”, these drugs work by activating a signal or pathway within the body. These specific agonists work by mimicking the hormone glucagon-like peptide 1 (GLP-1). GLP-1 is a signal between the digestive system and the endocrine system to help control sugar levels in the body. When food is digested, specialized cells within the small intestine and the colon release GLP-1, which makes its way to different locations throughout the body. When it attaches to receptors in the pancreas, it causes an increase in insulin production and a decrease in glucagon secretion, both of which lead to a reduction in blood sugar. GLP-1 agonists take the place of the hormone and boost the signal to the pancreas, making them an attractive option for treating type 2 diabetes.

After these medications had been on the market for a few years, clinicians noted that patients taking GLP-1 agonists also lost weight, leading to their use as weight loss treatments today. This weight loss effect is due to manipulation of the other targets of GLP-1 within the body: the brain and the vagus nerve. When GLP-1 reaches the brain, it attaches to receptors in regions called the hypothalamus and the nucleus of the solitary tract (NST). These regions are involved in normal appetite control, and GLP-1 works in these areas to reduce appetite signaling, making a person less hungry. The hormone also works to reduce hunger by attaching to the vagus nerve. The vagus nerve is the main connection between the brain and the gut, and it controls rates of digestion. When GLP-1 attaches to the vagus nerve, it slows down stomach emptying and digestion. This results in a person feeling full for a longer period of time. Therefore, when a patient takes a GLP-1 agonist, they have reduced hunger signaling which leads to less food intake and subsequent weight loss. 

The pros and cons of GLP-1 agonists

GLP-1 agonists have shown great success in clinical trials, with treatment groups showing 17% more weight loss during study periods in comparison to placebo controls. Treatments were well tolerated and only caused mild side effects such as nausea, diarrhea, indigestion, and headaches. Fortunately, most of these effects were dose dependent and were shown to decrease over time for a majority of patients. Interestingly, treatment with these medications has also led to improved cardiovascular functions, lower blood pressure, and reduced risk of kidney disease. Because obesity is a risk factor for these conditions, it leads us to ask a “chicken or the egg” question: are these improvements caused by GLP-1 agonists themselves or are they caused by weight loss? Some research has shown that GLP-1 agonists attach directly to blood vessels to lower blood pressure, but further studies are needed to fully understand the actions of these drugs in the body (both positive and negative).

The biggest drawbacks for GLP-1 agonists are cost and availability. The average list price for these medications is approximately $1000 per month. Insurance may cover some of the cost, but many users still have to pay out-of-pocket. A recent poll of GLP-1 agonist users revealed that 53% of all users said the drugs were unaffordable and 48% of users who discontinued their treatments cited cost as the main reason. Even if patients can pay these high costs, they might not be able to access these treatments. Increases in demand for these drugs have led to shortages and production issues. For example, a shortage of the drug tirzepatide (Mounjaro) began in 2022 and continued into 2024. Patients with diabetes may have felt a sense of déjà vu, as these same issues occur often with insulin treatments, leaving individuals searching for alternatives. The FDA has stepped in to manage the production of GLP-1 agonists, but some are still listed as “in shortage” on their website. Fortunately, litigation around the use of compounding and generic versions may increase availability and reduce the cost of these treatments in the future. 

Ultimately, GLP-1 agonists are a compelling option for people who want to lose weight. But who really needs them? For most people who wish to shed some pounds, diet and lifestyle modifications are enough, and current clinical guidelines only recommend medications such as GLP-1 agonists in extreme cases and as a supplement to other changes. Meanwhile, diabetic patients rely on these drugs to keep them alive and may not have other options due to ongoing insulin shortages. The availability of these drugs and who gains access to them should be the main focus of discussion and policy decisions in the future. It may take action similar to how Congress fought pharmaceutical companies to lower the cost of insulin treatments, but physicians and medical professionals who prescribe GLP-1 agonists should also be cognizant of the impacts they can have on this market. Educating the public on these drugs may also help individuals make more careful decisions about using them for weight loss. In any case, it will be interesting to follow the trajectory of these treatments as research and legal proceedings continue.

This article is meant for informative purposes only. As with any medical decision, it is strongly advised to speak with your doctor or healthcare professional before making any treatment decisions. 

Sources:

• Moore, P.W., Malone, K., VanValkenburg, D. et al. GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications. Adv Ther 40, 723–742 (2023). https://doi.org/10.1007/s12325-022-02394-w

• Watanabe, J. H., Kwon, J., Nan, B., & Reikes, A. (2024). Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. Journal of the American Pharmacists Association, 64(1), 133-138. https://doi.org/10.1016/j.japh.2023.10.002 

• Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. J Clin Invest. 2014 Oct;124(10):4223-6. Epub 2014 Sep 9. https://doi.org/10.1172/JCI78371 

• Zheng, Z., Zong, Y., Ma, Y. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024). https://doi.org/10.1038/s41392-024-01931-z

• Ferhatbegović, L., Mršić, D., & Macić-Džanković, A. (2023). The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in clinical diabetes and healthcare, 4, 1293926. https://doi.org/10.3389/fcdhc.2023.1293926 

• https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

• https://www.ncsl.org/state-legislatures-news/details/growth-volume-price-the-skinny-on-glp-1-medications

• https://www.medicalnewstoday.com/articles/glp-1-drugs-diabetes-drug-shortages 

• https://www.usatoday.com/story/news/health/2024/10/24/insulin-shortage-2024-diabetes-patients/75554041007/ 

• https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/

• https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize