Why Do GLP-1 Receptor Agonists (Ozempic and Wegovy) Seem to Treat Everything?

“It is rare that a drug becomes a household name and even rarer for one to become a superstar, but with its ability to grab headlines, Ozempic is the Taylor Swift of pharmaceuticals.”

Helen Thompson, journalist and editor, New Scientist

“The rise in prevalence of obesity and overweight, with plausible projections indicating that over 80% of adults in the USA could be affected by 2050, signals a public health crisis of unimaginable scale.”                                                                                                                          Ali H. Mokdad, PhD, Professor, Institute for Health Metrics, University of Washington, Seattle

Unprecedented has to be one of the most overused words in America today; yet it best describes the tidal wave of enthusiasm for glucagon-like peptide-1 receptor agonists (GLP-1RAs) for the treatment of obesity. There may have been a similar fervor in 1945 when penicillin was made commercially available, but in my 50 year career as an infectious diseases physician, I’ve certainly seen nothing like this.

When I last wrote on GLP-1RAs, I focused on the potential use for these drugs in the field of infectious diseases. (See,“Will the New Obesity Drugs (GLP-1 Agonists) Impact Infectious Diseases?,” Germ Gems, February 2, 2024). Given the mounting concern about the impact of obesity on global health and health expenditures, in today’s post, I epand the discussion and provide my take on why GLP-1RAs seem to treat everything.

GLP-1 receptor agonists; a recap. GLP-1RAs are a class of medications that mainly help manage blood sugar levels in people with Type 2 diabetes (T2D). They work by mimicking the effects of a GLP-1, a natural hormone which helps regulate appetite and blood sugar levels in the body. GLP-1RAs achieve this by binding to GLP-1 receptors in the body, primarily in the pancreas, digestive tract, and brain. Activation of GLP-1 receptors in the brain reward pathways promotes the sense of fullness and satiety, thereby reducing appetite, food intake and hunger with the end result of promoting weight loss.

Over the past four years in the U.S., there’s been a 700% increase use of GLP-1RAs in the number of patients without diabetes. Weight loss is the driving force underlying this epidemic of GLP-1RA use.

Obesity: a big and growing problem. Recently, the results of several comprehensive studies on the global obesity epidemic were published. According to these studies, globally by 2050, over half of all adults and a third of children will be overweight or obese. This is perceived as a global obesity crisis. But, you may ask, what constitutes obesity?

There’s an ongoing debate about the need for a better definition of obesity. Should one use “body roundness” rather than body mass index (BMI) to define obesity? (See, “Obesity needs a new definition beyond BMI, health experts argue,” Science News, January 14, 2025). Until that debate is settled, the Centers for Disease Control and Prevention (CDC) defines overweight and obesity as accumulations of excessive fat that present a risk to health, with a BMI over 25 considered overweight and over 30 obese. (The CDC provides an on-line BMI calculator if you would like to find out what your BMI is.)

Health problems associated with obesity. There are 16 common health problems correlated with obesity. (See, “Study: Obesity Linked with 16 Common Adverse Health Conditions,” Medpage Today, March 26, 2025). Of these 16, T2D comes in a close second to obstructive sleep apnea (7.74 vs 10.94 adjusted health risk, respectively).

For decades, metformin has been the go-to drug for the treatment of T2D. But, recent trends show that starting diabetes treatment with a GLP-1RA is increasingly popular, especially if obesity is a comorbid condition.

Safe and effective GLP-1RAs. To gain Food and Drug Administration (FDA) approval, both the safety and efficacy of the medication for a specific purpose must be established. To date, the FDA has approved 11 GLP-1RAs for treating diabetes, three of which are also FDA-approved for weight loss: semaglutide (brand name Wegovy or Ozempic), liraglutide (Saxenda), and tirzepatide (Zepbound or Mounjaro). While most of these agents are delivered by weekly injections, semaglutide (Reybelsus) is the first GLP-1RA that is also available for oral administration.    

GLP-1RAs have been shown to be extremely effective in managing obesity. Perhaps one of the most telling phenomena related to their efficacy has been the dwindling interest in bariatric surgery for the purpose of obesity management. (Bariatric surgery is an effective modality for obesity management but its invasive nature is unappealing to many patients, as well as to many non-surgical physicians.) The GLP-1RAs have also been shown to be quite safe. Nonetheless, they do have side effects.  

In January 2025, scientists at Washington University School of Medicine in St Louis published the results of a large study analyzing the benefits and risks of GLP-1RAs. (See, Xie, Y., Choi, T., Al-Aly, Z., “Mapping the effectiveness and risks of GLP-1 receptor agonists,” Nature Medicine, January 20, 2025). In addition to many health benefits from GLP-1RAs such as decreased risk of dementia and addiction, these researchers uncovered some heretofore unknown side effects involving the pancreas and kidneys. But, like all FDA-approved drugs, post-marketing surveillance studies for safety issues of GLP-1RAs are ongoing.

Capitalizing on GLP-1RAs. The soaring sales of Novo Nordisk’s Ozempic and Wegovny have given Denmark’s economy a huge boost. (See, Murray, A., “Hotdogs and Motorways: the ripples created by Denmark’s Ozempic and Wegovy boom,” BBC, February 20, 2025.) They have turned Novo Nordisk, already a pharmaceutical giant, “into one of Europe’s most valuable companies.” And, there appears to be no end to the market for GLP-1RAs. Some sources estimate that the global market for GLP-1RAs will reach $157.5 billion by 2035.

While the economic capitalization of GLP-1RAs is currently fed mainly by the obesity pandemic, the broad potential for capitalizing on GLP-1RAs to treat an array of other diseases is far more exciting to many health care professionals. Based on preliminary reports, promising results of studies of GLP-1RAs have popped up in diverse fields, including cardiovascular disease, cancer, neurology (stroke, Alzheimer’s dementia, Parkinson’s disease, HIV-related dementia), influenza, and perhaps most importantly, addiction disorders. And just this week, the New England Journal of Medicine published the positive results of a phase 3 clinical trial showing that semaglutide is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). (See, Sanyal, A.J. et al., “Phase 3 Trial of Semiglutide in Metabolic Dysfunction Associated Steatohepatitis,” New England Journal of Medicine, June, 5, 2025). (The global estimate for the mortality of MASH is more than 140,000 deaths per year.)

Why do GLP-1RAs seem to treat everything? Time will tell whether indications for using GLP-1RAs to treat conditions other than weight loss and diabetes will pan out. But in the meantime, one can speculate about the answer to this question: “Why do GPL-1RAs seem to treat everything?” (See, Thompson, H., “Why do Ozempic and Wegovy seem to treat everything?”, New Scientist, December 2, 2024).

In my opinion, it’s all about the immune system—in particular, the cells called macrophages that are found in all organs. (Derived from the Greek words “makros” (large) and “phagein” (to eat), “macrophage” literally means “big eater.”) Macrophages from many tissues have been shown to express GLP-1 receptors. And, as macrophages are essentially found in every tissue in the body,  I hypothesize that a key target for GLP-1RAs is the “big eater”—the macrophage. That’s my hypothesis as to why Ozempic and Wegovy seem to treat everything.