The GLP-1 Receptor Agonist Revolution: From Medical Breakthrough to Trillion Dollar Industry

“Few medications have had such a meteoric rise as semaglutide (Ozempic, Wegovy) and tirzepatide (Zepbound), the GLP-1-based treatments for obesity that have captivated society and quickly become household names.”

Christopher McGowan, MD, University North Carolina

“When people hear about celebrities rapidly losing a ton of weight with these drugs (GLP-1s), it gives the impression of a quick fix. That perception ignores the underlying science and the medical guidance required for success.”

Michael Snyder, MD, Rose Medical Center, Denver Colorado

Few medical breakthroughs have generated the cultural phenomenon we’re seeing today surrounding the glucagon-like peptide-1 receptor agonists (GLP-1RAs). Hailed as miracle drugs, Ozempic and Wegovy (basically both are semaglutide in different doses) and Zepbound (tirzepatide) have been met with a tidal wave of enthusiasm. They have revolutionized the treatment of obesity.

The GLP-1 story represents not only a medical revolution but an economic one as well—culminating in Eli Lilly becoming the first healthcare company to reach a trillion-dollar valuation, driven largely by its GLP-1RA tirzepatide (marketed as Mounjara for Type 2 diabetes and Zepbound for obesity). And even greater sales of GLP-1RAs are sure to follow.

Cost has been the main barrier to wide-spread use of GLP-1RAs for weight management. That barrier no longer exists. On December 23, 2025, the U.S. Centers for Medicare and Medicaid Services unveiled a voluntary plan to cover the drugs for weight management.

In this post, I provide an update on the revolution created by GLP-1RAs and include a cautionary note about the limits of their success.

A growing crisis. The obesity pandemic that began in the 1970s in the U.S. and spread to westernized countries in the following decade has reached crisis proportions. Currently, about 41% of U.S. adults are obese, and 38% of the global population are either overweight or obese. (The Centers for Disease Control and Prevention defines overweight and obesity as accumulations of excessive fat that presents a risk to health, with body mass index of over 25 considered overweight and a body mass index of over 30 obese.)

Globally by 2050, over half of all adults and a third of all children will be overweight or obese. This global obesity crisis will have profound implications for healthcare systems worldwide as obesity is correlated with numerous health problems including, but not limited to, Type 2 diabetes (T2D), heart disease, stroke, hypertension, and sleep apnea. (In the U.S., over 38 million adults have diabetes, 90-95% of whom have T2D.)

A revolutionary solution. The Danish pharmaceutical giant Novo Nordisk developed Ozempic for T2D and Wegovy for chronic weight management. The origin of these GLP-1RA drugs is based on research into the natural gut hormone glucagon-like peptide-1 (GLP-1), a hormone that helps regulate appetite and blood sugar levels in the body.

GLP-1RAs are a class of medications that mimic the effects of GLP-1 and work by binding to GLP1-receptors located primarily in the pancreas, digestive tract, and brain. In the pancreas, GLP-1RAs enhance glucose-dependent insulin secretion and lower blood glucose, making them effective treatments for T2D. But their effects extend far beyond diabetes management.

GLP-1 receptors are widely expressed in the brain, particularly in reward pathways. Activation of these brain receptors promotes the sense of fullness and satiety thereby reducing appetite, food intake, and hunger—ultimately promoting significant weight loss. Studies demonstrate that treatment with a GLP-1RA along with diet and exercise can result in up to 15% body weight loss. (Moiz, A., et al., “The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions,” eClinical Medicine, July 17, 2025).

From 2019-2023 in the U.S., there was a 700% increase in the use of GLP-1RAs among patients without diabetes. (Mahase, E., “GLP-1 agonists: US sees 700% increase over four years in number of patients without diabetes starting treatment,” BMJ, July 23, 2024). Weight loss is the driving force underlying this epidemic of GLP-1RA use.

Side effects. The Food and Drug Administrations (FDA) has approved three GLP-1RAs specifically for weight loss: semaglutide (Wegovy, Rybeisus), liraglutide (Saxenda), and tirzepatide (Zepbound). All have proven to be quite safe but they do have side effects.

The main side effects are gastrointestinal issues such as nausea, vomiting, diarrhea, abdominal pain, and constipation. These generally occur when starting treatment but usually improve over time. Other side effects include loss of appetite and injection site reaction. Potential complications include gallstones or, in rare cases, pancreatitis.

As is true for all FDA-approved drugs, post-marketing surveillance studies for safety issues of GLP-1RAs are ongoing. As the number of patients taking GLP-1RAs grows exponentially, one can anticipate that more side effects will be reported. Patients and physicians must therefore remain vigilant about other side effects and potential complications from using these drugs.

Not a perfect solution. The enthusiasm for GLP-1RAs is understandable given their dramatic effectiveness for weight loss. Nonetheless, they have drawbacks that are important to acknowledge.

Taking a GLP-1RA for weight loss is a life time commitment. This represents a practical challenge for many patients.  (McGowan, C., “I No Longer Think GLP-1s Are the Answer,” MedPage Today, January 20, 2025). Studies suggest that a substantial portion of patients stop taking these medications within the first year, often due to side effects, cost, or the burden of administrating the drug. When patients discontinue GLP-1RAs, weight regain is common, raising questions about the sustainability of this therapeutic approach.

One of the most concerning issues with rapid weight loss induced by GLP-1RAs is the accompanying loss of lean muscle mass. (Prado, C.M., et al., “Muscle matters: the effects of medically induced weight loss on skeletal muscle,” Lancet, September 9, 2024). While patients lose significant amounts of fat, they also lose muscle tissue, a phenomenon that can be particularly problematic for older adults who are already at risk for sarcopenia (age-related muscle loss). Loss of muscle mass can lead to decreased strength, reduced metabolic rate, and increased risk of falls and fractures. This has led experts to emphasize the critical importance of resistance training and adequate protein intake for patients taking GLP-1RAs, though compliance with these recommendations is often suboptimal.

These drawbacks do not negate the value of GLP-1RAs, but they do underscore that these medications are not a magic bullet. Instead, they represent a powerful tool that must be used thoughtfully, with careful patient selection, appropriate monitoring, and realistic expectations about long-term outcomes.