Casey Arnold, who lives in a suburb of Houston, United States, spent years trying to quit smoking. He had tried nicotine patches. He didn’t get it. He tried to quit cold turkey, but it made him cranky. At other times, the idea of quitting smoking made him so anxious that he smoked more to ease his fears.
When he stopped smoking permanently in the winter of 2023, at the age of 55, he had been smoking for four decades and smoked two packs a day. But this time it was a new type of weight loss medication that helped her quit.
GLP-1, short for glucagon-like peptide 1, is a natural hormone that stimulates the production and release of insulin, slows digestion, curbs appetite, and diverts the brain’s attention to food. GLP-1 agonist drugs, such as exanetide, tirzepatide, and semaglutide, mimic this hormone. They were originally developed as treatments for diabetes, but as more people began taking them, researchers found that these medications are effective for many more conditions than diabetes and weight loss.
The Food and Drug Administration (FDA) has just approved semaglutide, the active ingredient in Wegovy, for the treatment of obesity and reducing the risk of heart attack and stroke. ictus in obese patients and patients with heart disease. But as the number of people taking these drugs increases, doctors and researchers are discovering unexpected health benefits for conditions for which treatments have been limited, such as addiction, heart failure and kidney disease.
Arnold quit smoking while participating in a clinical trial examining the potential of GLP-1 agonists as a treatment for tobacco addiction.
“It was totally the opposite of when I tried to quit in my earlier years,” Arnold says; “I was surprised at how calm I was, compared to what I used to think about quitting.” Instead of anxiety and anger, he felt at peace, and his anxiety disappeared.
“It’s been an avalanche across different patient populations,” says Mark Petrie, a cardiologist at the University of Glasgow in the United Kingdom, whose research focuses on the use of GLP-1 agonists in patients with heart failure. “It’s good news overall.”
In a study published last year, researchers tested semaglutide as a treatment for HFpEF in non-diabetic patients. The result: Patients who received the drug showed fewer symptoms and reported a better quality of life, compared to those who received the placebo. Patients who received the drug had lower levels of C-reactive protein, which is a marker of inflammation.
“This is a great finding,” says James de Lemos, a cardiologist at UT Southwestern Medical Center in Dallas, United States, who was not involved in the study. The study was too small to determine whether semaglutide can reduce the risk of hospitalization or death, but given the notable improvement in patients’ quality of life, it shows promise.
Although some of these benefits are likely due to weight loss, that is only part of what makes this treatment effective.
According to Amanda Vest, a cardiologist at the Cleveland Clinic (USA) specializing in the treatment of patients with heart failure, these medications are also cardioprotective and reduce inflammation, which is known to be one of the triggers of heart failure. “We need to continue thinking more broadly than just the number on the scale,” Vest says.
For patients with the other main type of heart failure (heart failure with reduced ejection fraction), there is less evidence, so far, that these drugs are effective. More trials are being done to determine which types of patients will benefit from using these medications.
For patients with severe chronic kidney disease, “the mortality rate ranges between 10% and 20% annually,” says Katherine Tuttle, a nephrologist at the University of Washington Medicine (USA); “this is on par with the worst malignant tumors.”
As a couple of recent studies have shown, the GLP-1 agonist dulaglutide helps patients with chronic kidney disease and diabetes. In a recent trial of the effect of semaglutide in patients with chronic kidney disease and type 2 diabetes, the treatment was so effective in slowing the progression of chronic kidney disease that the clinical trial was stopped early so that all patients of the trial could benefit from the drug.
“It’s the only semaglutide trial that has been stopped early for efficacy reasons,” says Tuttle, who is on the trial’s executive committee. “To stop a trial early for efficacy, the bar is very high,” including strong enough evidence of its effectiveness that it is no longer considered ethical to continue giving placebos to patients.
As Tuttle points out, the effects on the kidneys are only partly due to the reduction of risk factors such as blood pressure, blood sugar, and weight. Other benefits are likely due to reduced inflammation.
“They have a profound anti-inflammatory effect,” says Tuttle; “In our field, the importance of inflammation is really being recognized, especially in kidney damage caused by diabetes.”
The results of the trial will be published later this year.
For a growing number of patients taking GLP-1 agonists, such as Ozempic or Mounjaro, a surprising side effect has been unexpected pregnancy, which for some patients has come after years of struggling with infertility. Although more research is needed to explore the relationship between GLP-1 agonists and pregnancy, it has become such a common phenomenon that “Ozempic babies” has become a buzzword. Meanwhile, experts believe several factors are responsible.
The first factor is the fact that GLP-1 agonists cause a delay in gastric emptying, which can cause the body to absorb oral contraceptive pills at a slower rate. “These drugs alter that particular part of the drug absorption phase,” says Archana Sadhu, an endocrinologist at Houston Methodist Hospital, USA, adding that this effect may be especially prominent during dose increases. This means that oral contraceptives may not be as effective.
The second factor is the relationship between polycystic ovary syndrome (PCOS) (the leading cause of infertility in women) and insulin resistance.
“Insulin resistance deregulates the ovarian cycle,” says Sadhu. Insulin resistance can cause infertility by altering fertility-related hormones such as estrogen and testosterone and affecting the release of eggs from the ovaries. When patients start taking GLP-1 agonists, their insulin resistance is reduced, which promotes fertility.
However, the effects of these drugs on pregnancy are still unknown, so it is important that patients talk with their doctors about any plans to become pregnant, as well as contraceptive strategies, which may include the addition of a second method. to increase oral contraceptive pills, or switch to a different method.
Since Ozempic and Mounjaro have become more common, patients have reported several unexpected side effects, such as a decreased desire to smoke or drink. Although more research is needed, the part of the brain responsible for craving food is thought to overlap with the part of the brain responsible for craving addictive substances, says Luba Yammine, an addiction researcher at UTHealth Houston.
For doctors working in this field, earlier versions of these GLP-1 drugs showed enormous potential as anti-addiction medications.
“We have far fewer medications” to treat addiction, and many patients have difficulty accessing them, says Christian Hendershot, an addiction researcher at the University of North Carolina School of Medicine (United States). Additionally, this field receives less research funding than other diseases.
Yammine became interested in studying the effect of GLP-1 agonists on addiction while working in primary care, where she had several smoking patients with diabetes. Ella yammine advised her patients to quit smoking, prescribing nicotine patches or the drug buproprion, to help them kick the habit. But most of the time these strategies failed.
“It’s hard to quit smoking, period,” says Yammine; “The vast majority of smokers want to quit, but even with the use of these therapies, many of them are unable to do so.”
To help these smokers with their diabetes, she prescribed them GLP-1 agonist medications, only to discover when they returned for a follow-up that they had stopped smoking. When she asked them what had happened, her response was that suddenly her craving for smoking had disappeared. “It was a very interesting find,” says Yammine.
This occurred frequently enough that Yammine decided to explore the impact of these GLP-1 receptor agonists on addiction through a clinical trial.
Yammine and his colleagues led a pilot study, in which 46 percent of participants who received exanetide, plus nicotine patches and smoking cessation counseling, were able to quit, compared to 26 percent of participants who received nicotine patches, counseling and a placebo. Yammine and her collaborators are following up with a larger trial. They are also planning another trial with semaglutide.
For study patients who received exanetide, their weight after quitting smoking was 2.5 kilograms less than those who received placebo, a side effect that may help offset the weight gain often associated with quitting smoking. .
“This weight gain is very problematic,” Yammine says, adding that many patients fear quitting or relapsing due to concerns about weight gain, and that it can also increase their risk of developing weight-related diseases, such as type 2 diabetes.
For Arnold, who enrolled in a follow-up trial being conducted by Yammine, the months he participated in the trial were characterized by both the peace of mind surrounding his efforts to quit smoking and minimal weight gain. Since she completed the trial, she has been able to maintain her efforts to quit smoking, although she has gained some weight. “I don’t have cravings,” Arnold says; “it’s this weight gain that bothers me.”
Arnold, who works at an HVAC company, would very much like to go back on exanetide, but like so many other patients who have experienced the benefits of GLP-1 receptor agonists, he is afraid. It’s getting too expensive. A month’s supply costs about $1,000, and without FDA approval for use as an anti-addiction drug, most U.S. medical insurance companies won’t pay for it.