Semaglutide and HIV
Semaglutide (Ozempic, Wegovy) is a long-acting compound that mimics a hormone used by the body called GLP-1 (glucagon-like peptide 1). Semaglutide belongs to a class of drugs called GLP-1 receptor agonists.
GLP-1 is released by cells in the intestine in response to food entering the intestine. Some tissues have receptors for GLP-1, such as the following:
- pancreas gland
- stomach
- kidney
- heart
- brain (in the hypothalamus)
When GLP-1 binds to its receptors, the effect is to slow the movement of food in the intestine, decreasing appetite. GLP-1 agonists were initially developed for the treatment of type 2 diabetes. Over time, researchers have found that some GLP-1 agonists (such as semaglutide) can cause weight loss in people who can tolerate them.
Note that GLP-1 agonists can cause a range of side effects, including nausea, vomiting, diarrhea and constipation. Some people also experience a decrease in muscle mass. For many people, these side effects are mild and resolve over time. However, for some people they can be bothersome or even severe. As a result, not everyone prescribed a GLP-1 agonist can tolerate it over the long term. What’s more, researchers are finding that a minority of people who are treated with drugs such as semaglutide do not always respond to it. The reasons for this non-response are not known.
In addition, improvements in blood sugar and the health of the heart and other organs has been found in users of GLP-1 agonists.
The impact of GLP-1 agonists on human health is an area of intense research. As there are receptors for GLP-1 in different organs/tissues, it is possible that this class of drugs can have an impact on many conditions. One study suggests that GLP-1 agonists have potential in the following areas:
- substance use disorder
- psychotic disorders
- seizures
- neurocognitive disorders (including Alzheimer’s disease and dementia)
- coagulation disorders
- cardiometabolic disorders, including liver inflammation
- infectious illnesses
- some respiratory conditions
However, these other potential uses for GLP-1 agonists (and related drugs) should be considered preliminary and require well-designed clinical trials to better understand the effects of these drugs in different conditions.
Also noteworthy is that the benefits of GLP-1 agonists quickly fade once cessation of these drugs occurs.
In HIV
HIV causes excess levels of inflammation and immune activation. These effects are only partially normalized with the use of effective HIV treatment (ART). As a result, researchers are seeking multiple therapies to try to further reduce excess inflammation. Therefore, semaglutide and similar drugs need to be tested in clinical trials over the long-term in people with HIV.
HIV is also associated with an increased risk of neurocognitive issues. Before ART was available, severe neurocognitive issues (such as dementia) were a growing problem in people living with HIV. However, the widespread availability of ART has meant that HIV-related dementia is now rare.
In the current era, some people with HIV have developed obesity (as have many people without HIV). The cause of this excess weight gain is unclear but may be related to overall trends in society (excess intake of carbohydrates and calories, less physical activity). In some cases, exposure to HIV treatment may have played a role. Obesity is associated with an increased risk for type 2 diabetes, and sometimes this can affect the functioning of the brain.
Preliminary results from clinical trials suggest that GLP-1 agonists are generally safe in people with HIV. In one study, semaglutide resulted in weight loss (in obese people) of nearly seven kilograms per year.
What’s to come
In this issue of TreatmentUpdate, we introduced some studies with semaglutide, a commonly used GLP-1 agonist. Currently, the availability of potent GLP-1 agonists is restricted, particularly on provincial and territorial drug subsidy programs. However, in the future, possibly sometime in 2026, a major patent on semaglutide will expire in Canada and perhaps generic competition may result in price reductions and less restrictive access.
Drugs such as semaglutide work on one protein. But newer drugs and combinations of drugs designed for treating obesity and type 2 diabetes tend to work on two or more proteins in the body. As a result, these newer drugs, such as tirzepatide (Mounjaro, Zepbound) are associated with a greater degree of weight loss than semaglutide.
—Sean R. Hosein
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