Exploring the Expanded Potential of GLP-1s


As demand for GLP-1 receptor agonist medications increases, researchers are hopeful these drugs can be used for more indications than those that currently exist.

GLP-1 receptor agonists (GLP-1RAs) have made waves in the pharmaceutical industry over the past few years for their treatment of type 2 diabetes (T2D) and obesity. With semaglutide (Ozempic, Wegovy), exenatide (Byetta, Bydureon), and other GLP-1s emerging as some of the most popular prescription drugs in the US, researchers are exploring the scope of these drugs for other conditions such as cardiovascular disease (CVD), alcohol use disorder, smoking cessation, and more.

“Smoking cessation is only one of a variety of indications for which the popular drugs hold promise. They’re already approved by the [FDA] for treating type 2 diabetes and obesity, and, most recently, protecting against cardiovascular death, myocardial infarction, and stroke,” wrote Rita Rubin, MA, for JAMA.1

Key Takeaways

  • With GLP-1RAs taking the prescription drug market by storm, researchers are aiming to expand the clinical uses for these drugs.
  • GLP-1RAs are already approved for treating obesity, T2D, and now CVD.
  • Researchers are now assessing the efficacy of these drugs to treat conditions such as Alzheimer disease, substance use disorder, and smoking cessation.

Within many of the clinical trials testing GLP-1s for use in treating T2D and obesity, researchers have found promising results that could make them useful for other conditions.

In 2023, semaglutide overtook adalimumab, an anti-tumor necrosis factor a monoclonal antibody used to treat autoimmune diseases, as the highest-selling drug in the US.2 As demand increases and clinical trials continue, researchers are aiming to further stretch the clinical uses of GLP-1s for patients with chronic medical conditions.

Wegovy GLP-1 utensils

With GLP-1s emerging as some of the most popular prescription drugs in the US, researchers are exploring the scope of these drugs for other conditions. | image credit: K KStock / stock.adobe.com

Current Clinical Uses for GLP-1RAs

GLP-1RAs are an effective first-line treatment to treat both T2D and obesity. More recent indications have granted the drugs approval for CVD as well.

“Starting in 2016, the first in a series of cardiovascular outcome studies demonstrated that long-acting GLP-1RAs reduce the rates of myocardial infarction, stroke, cardiovascular death, and all-cause mortality in people with T2D,” wrote Daniel J. Drucker, MD, FRCPC, professor of medicine at the University of Toronto.3 “More recent studies have extended the cardiovascular benefits of GLP-1R agonism to people with obesity, and subjects with heart failure and preserved ejection fraction.”

Amit Khera, MD, MSc, director of the UT Southwestern preventive cardiology program, discussed the GLP-1RA evolution from treating CVD in T2D patients to treating CVD in those without.

“These GLP-1 receptor agonists are everywhere, as weight loss agents, as diabetes medications. So, what’s different here? We have evidence that if you treat patients with diabetes with semaglutide, you will lower cardiovascular events. We knew that, but we didn’t know is in the absence of diabetes, would you see the same thing,” said Khera in a JAMA interview.4

Khera’s comments were in response to a question regarding the SELECT clinical trial (NCT03574597) released in November 2023. Results of the trial were successful for 2 at-risk groups: individuals with obesity or overweight, and those without T2D diabetes aiming to treat cardiovascular complications.

“In a large, international clinical trial, people with obesity or overweight but not diabetes taking semaglutide for more than 3 years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease and lost an average of 9.4% of their body weight,” wrote authors of the study.5

Now that GLP-1s are commonplace in the treatment of T2D, obesity, and CVD, researchers are exploring the drugs’ indications for other conditions such as substance use disorder, addiction, Alzheimer disease, and more.1

READ MORE: Weight-Loss Drugs Fuel Rise in US Prescription Spending

GLP-1s to Treat Other Conditions

Luba Yammine, PhD, MSN, associate professor in the department of psychiatry and behavioral sciences at UTHealth Houston, published an article on exenatide’s ability to help patients quit smoking.1

“Yammine’s team randomly assigned 84 people who smoked and were prediabetic, overweight, or both to receive weekly injections of exenatide or a placebo for 6 weeks. At the end of the study, about 46% of the participants who received exenatide had quit smoking, compared with 27% of the placebo group. Plus, participants in the exenatide group weighed about 5 [pounds] less on average than those who got the placebo,” wrote Rubin about the study.1

For substance use disorder, however—specifically for those excessively consuming alcohol or cocaine—evidence of GLP-1 efficacy has only been anecdotal. One study featuring just 3 participants showed that exenatide only helped 1 of the 3 stop using cocaine by the end of the 6-week study period. However, trial results for GLP-1s that treat alcohol use disorder were more widespread.

“A study that used data from nationwide registers in Denmark found that patients taking GLP-1[RAs] had fewer alcohol-related events than those taking dipeptidyl peptidase 4 inhibitors, or gliptins, another class of drugs used to treat type 2 diabetes,” continued Rubin.1

Finally, in more recent clinical trials, patients receiving semaglutide were reported 24% less likely to experience progression of kidney disease or death, while a different group of patients were less likely to report cognitive impairment after being treated with semaglutide.1

While deliberation on GLP-1s’ uses for obesity and T2D seems to be a thing of the past, testing for their uses on other conditions is now taking shape. It’s only a matter of time before these drugs—which are already flying off pharmacists’ shelves—receive more crucial indications.

READ MORE: GLP-1 Demand to Continue Increase as More Benefits Are Discovered

1. Rubin R. Could GLP-1 receptor agonists like semaglutide treat addiction, Alzheimer disease, and other conditions? JAMA. Published online April 19, 2024. doi:10.1001/jama.2024.1017
2. Enormous demand for weight-loss drugs drives up total U.S. prescription spending. American Society of Health System Pharmacists. April 24, 2024. Accessed May 2, 2024. https://www.prnewswire.com/news-releases/enormous-demand-for-weight-loss-drugs-drives-up-total-us-prescription-spending-302125178.html
3. Drucker D. The GLP-1 journey: from discovery science to therapeutic impact. JCI. 2024;134(2). doi.org/10.1172/JCI175634
4. Abbasi J. Highlights from AHA 2023—new risk calculator, semaglutide and CVD, and more. JAMA. 2023;330(23):2237–2240. doi:10.1001/jama.2023.22707
5. Major CVD event risk cut by 20% in adults without diabetes, with overweight or obesity. AHA. November 11, 2023. Accessed May 7, 2024. https://newsroom.heart.org/news/major-cvd-event-risk-cut-by-20-in-adults-without-diabetes-with-overweight-or-obesity
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