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  • Writer's pictureP.K. Peterson

Will the New Obesity Drugs (GLP-1 Agonists) Impact Infectious Diseases?

“There’s never been anything like the revolution in the treatment of obesity that we are now living through.”

-Arthur L. Caplan, PhD, American ethicist and professor of bioethics, New York    University Grossman School of Medicine


“The latest generation of anti-obesity drugs has taken the world by storm, thanks to their effectiveness at treating diabetes and reducing weight. But these drugs also have a less well-known superpower: the ability to suppress inflammation.”

Mariana Lenharo, science and health journalist

 


The February 7, 2023 issue of The Atlantic featured this article: “Older Americans Are About to Lose a Lot of Weight.” Recently, I’ve read a number of similar articles all touting the extraordinary effectiveness of the glucagon-like peptide 1 (GLP-1) agonists—the new weight loss drugs. I’ve read these articles with interest not only because I’m an overweight older adult but also because of the potential impact GLP-1 drugs could have on infectious diseases. As we are now in the so-called “Age of GLP-1 Agonists,” i.e., Wegovy, Ozempic, Rybelsus, Saxenda, Trulicity, etc., I thought it time for a Germ Gems post on the GLP-1 agonists and their implications for other diseases.

The obesity pandemic. In the U.S., the obesity pandemic started in the late 1970s and emerged during the next decade in Westernized countries. Currently, about 41% of U.S. adults are obese, and 38% of the global population are either overweight or obese.

Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. A body mass index (BMI) over 25 is considered overweight, and over 30 obese.


(The Centers for Disease Control and Prevention provides a nifty on-line “BMI Calculator” if you would like to find out what your BMI is.)


Obesity is a chronic disease and needs to be treated like any other chronic disease. As Ania Jastreboff, MD, PhD, director of the Yale Obesity Research Center stated: “[O]besity is not a choice.” Genes and other biological factors play a role in obesity, and they’re involved in “getting hooked” on processed or junk food. And eating large amounts of ultra-processed fast food is a key factor in development of obesity.    


All weight-loss programs for obese people recommend a well-balanced diet along with exercise. Unfortunately, these measures ultimately fail most patients. For obese patients with serious health problems, gastric bypass or bariatric surgery may be recommended. This procedure does work and is generally safe but, like all surgeries, has risks, e.g., anesthesia,excessive bleeding, and infection. Some doctors, therefore, herald the advent of GLP-1 agonist therapy as a game changer in the fight against obesity. (The therapy will also be a game changer for the pharmaceutical industry as some analysts forecast that by 2030, the market for GLP-1 agonists will yield up to $200 billion per year.)


What are the GLP-1 agonists and how do they work? GLP-1 agonists are a class of medications that mainly help manage blood sugar levels in people with Type 2 diabetes. GLP-1 agonists work by enhancing glucose-dependent insulin secretion and lowering blood glucose.


GLP-1 receptors are also widely expressed in the brain. Therefore, in addition to their effects on insulin secretion, GLP-1 agonists also affect brain reward pathways. Activation of GLP-1 receptors in 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.

Studies demonstrate that treatment with a GLP-1 agonist along with a diet and exercise program will result in up to 15% body weight loss. The Food and Drug Administration has approved at least 10 GLP-1 agonists for treatment of type 2 diabetes, most of which can also be used potentially to treat obesity.


Patients who’ve been struggling with obesity should consult with their primary care doctor (or an experienced specialist) about whether one of these GLP-1 agonists makes sense for them. These drugs are generally safe. The biggest downsides are: (1) the inconvenience of daily or weekly self-injection for most of them—Rybelsus is the exception and is taken by mouth once a day;  and (2) the cost— GLP-1 agonists range in cost from $800 per month to over $1300 per month. At present, it appears that treatment with any of these weight loss drugs is life-long.


Medicare doesn’t cover drugs prescribed for weight loss. A survey from the Business Group on Health, however, found that 92% of large employers covered GLP-1s for diabetes in 2023, and 46% covered them for weight loss.


Link between obesity and infectious diseases.  In the January 2022 article in Nature, “Obesity and infectious diseases: pathophysiology and epidemiology of a double pandemic condition,” researchers reviewed the impact of obesity on COVID-19 and other infectious diseases (skin infections, urinary tract infections, and respiratory tract infections), and found an increased risk of all these infections in obese people. And in Nature Medicine in May 2023, British researchers reported that obesity also accelerates the loss of COVID-19 immunity conferred by vaccination.

 

Anti-inflammatory properties of GLP-1 agonists. In a January 26, 2024 article in Nature News, “Obesity drugs have another superpower: taming inflammation,” journalist Mariana Lenharo discusses the emerging evidence that GLP-1 agonists “dial down inflammation in the brain, leading scientists to hope the compounds are of value in treatment of Parkinson’s and Alzheimer’s disease, both of which are characterized by brain inflammation.”


Clinical trials of GLP-1 agonists are already underway in Parkinson’s disease and Alzheimer’s disease. Because an overactive immune response plays a key role in the pathogenesis of many infectious diseases, such as acute COVID-19, it seems likely that we’ll see clinical trials of GLP-1 agonists in obese and non-obese patient populations with sepsis (a life-threatening complication of a number of serious infections).

GLP-1 agonists and the brain. Given what’s been reported with GLP-1 agonists and their effects in the brain, this February 9, 2024 report in WebMD Health News, “Study Suggests Mind-Body Benefits of GLP-1s,” wasn’t at all surprising. In this study, researchers found that people with diabetes who started taking GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than diabetics who didn’t take GLP-1 agonists.


I spent several decades of my career treating patients with drug or alcohol addiction—another chronic medical condition in which craving is a key component. Hence, I’m even more excited about the potential role of GLP-1 agonists in the management of these devastating chronic diseases. (See “The role of glucagon-like peptide [GLP-1] in addictive substance disorders,” British Journal of Pharmacology, February 17, 2022;  “Use of GLP-1 Receptor Agonists to Treat Substance and Alcohol Use Disorders Is Promising, but Premature,” UNC Health Newsroom, December 5, 2023.)


Using GLP-1 agonists to treat obesity may be the game changer that some people claim. But if the studies on using these drugs to treat addictive substance disorders bear out, it would revolutionize medicine.

 

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1 Comment


jnbob
Feb 21

Interesting! Thank you!

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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