Weight loss: GLP-1 agonists may increase risk of stomach paralysis

• There has recently been a lot of attention around using GLP-1 agonists for weight loss.
• Past research shows that GLP-1 agonists have potential side effects, including stomach paralysis.
• New research from the University of British Columbia provides more evidence linking the use of GLP-1 agonists with an increased risk for stomach paralysis, pancreatitis, and bowel obstruction.

Over the last year, the news and social media have been saturated with headlines, advertisements, and other information about using medications like Ozempic and Wegovy for weight loss.

Previous research has shown these medications — which are a class of drugs called GLP-1 agonists — to be effective in helping people lose weight.

However, just like all medications, GLP-1 agonists also have potential side effects, such as nausea, vomiting, diarrhea, and headache.

And because one of the things GLP-1 agonists do is slow the emptying of the stomach, past studies also link GLP-1 agonists to a possible risk of gastroparesis or stomach paralysis.

Now, new research from the University of British Columbia provides more evidence linking the use of GLP-1 agonists with an increased risk for serious gastrointestinal issues, including stomach paralysis, pancreatitis, and bowel obstruction.

This study was recently published in JAMA.

Gastrointestinal issues from GLP-1 agonists

According to Mohit Sodhi, researcher and a fourth-year medical student at the University of British Columbia and the first author of the new study, he and his colleagues decided to study the effect of GLP-1 agonists on the gastrointestinal system after noticing a person in the emergency room who had significant unexplained nausea and vomiting.

“Of note, he recently started Ozempic for weight loss,” he explained to Medical News Today. “I had seen a number of anecdotal reports, case reports, and literature describing similar symptoms as this particular patient. Additionally, millions around the world have started using these medications to assist in [their] weight loss goals.”

This is not the first research to examine a link between the use of GLP-1 agonists and potential gastrointestinal problems.

A study published in January 2022 linked several gastrointestinal problems — including abdominal pain, indigestion, abdominal distension, and gastroesophageal reflux disease — to the use of GLP-1 agonists.

Research published in December 2022 also reported the use of GLP-1 receptors was significantly associated with gastrointestinal adverse effects.

How do GLP-1 medications help with weight loss?

Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are a type of medication used to help manage type 2 diabetes.

GLP-1 is a hormone naturally found in the small intestine. These medications mimic this hormone, triggering the effects of the GLP-1 hormone. Because of this mechanism, GLP-1 agonists can:

• tell the pancreas to release insulin
• block the secretion of glucagon, a hormone used to raise blood sugar levels
• slow digestion so food stays in the stomach longer, making you feel fuller for longer.

Types of GLP-1 agonists include:

• semaglutide (Ozempic, Wegovy, and Rybelsus)
• liraglutide (Saxenda and Victoza)
• exenatide (Byetta)
• dulaglutide (Trulicity)
• tirzepatide (Mounjaro) — targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) hormones.

Most GLP-1 agonists, such as Ozempic, Wegovy, and Saxenda, are injected medications. Rybelsus comes in pill form.

Currently, only Wegovy and Saxenda are approved by the Food and Drug Administration (FDA) as weight loss drugs.

However, researchers show there is a growing number of people without diabetes using or interested in using GLP-1 agonists off-label for weight loss.

The amount of weight a person may lose on a GLP-1 agonist varies. Previous research shows the amount can vary between 4% and 17%.

How much weight is lost depends on the person’s health and what lifestyle changes they make, such as exercise and a healthy diet.

GLP-1 agonists vs. bupropion-naltrexone

For this study, Sodhi and his team examined health insurance claim records for about 16 million people in the United States to look for prescriptions of either semaglutide or liraglutide between 2006 and 2020.

The study included data from people with a recent history of obesity and excluded those with diabetes or who have been prescribed another anti-diabetes medication.

Scientists analyzed the data to see how many people developed one of four gastrointestinal conditions — pancreatitis, bowel obstruction, gastroparesis, and biliary disease. Those findings were then compared to people who took a combination of bupropion and naltrexone for weight loss.

Researchers found that the participants who took GLP-1 agonists had a little over nine times higher risk of developing pancreatitis, 4.22 times higher risk of having a bowel obstruction, and 3.67 times increased risk for gastroparesis, compared to people who took bupropion-naltrexone.

“We are not entirely surprised [by these results]. There have been many anecdotal reports and case reports in the literature of these adverse events in patients using these medications for weight loss. However, no epidemiologic study investigated this risk,” Sodhi said.

“We are strong proponents for informed patient consent. We believe it is crucial for patients to have a full understanding of the potential adverse events associated with any medical therapy that they choose to pursue. We also hope that our study can help inform healthcare providers and make them aware of these risks,” he added.

How much of an increased risk?

After reviewing this study, Dr. Rami Bailony, an obesity specialist and CEO of Enara, who was not involved in the research, told MNT that his initial reaction was one of cautious interest as it is important to interpret the results in a broader context.

“While relative risk percentages might sound alarming, the absolute risk, or the actual number of people affected, can be quite small,” said Dr. Bailony.

“It’s essential to differentiate between the two to give patients a clear understanding of the real-world implications. While statements like ‘a nine times increased risk’ can sound alarming at first glance, it’s crucial to understand what that actually means in real-world terms,” he explained.

“When the study says there’s a nine times increased risk of pancreatitis, it’s speaking in relative terms. But if we delve into the absolute risk, the actual numbers paint a different picture. For instance, if we look at pancreatitis and its reported incidence rate, it means that for every 1,000 people taking the medication for a year, roughly eight might experience the condition. So, while the relative risk seems high, the absolute number of people affected is relatively small.”
— Dr. Rami Bailony

“This distinction between relative and absolute risk is vital for patients to understand, so they can make informed decisions based on the real-world implications of the data, rather than just the headline numbers,” he said.

Who is more likely to have side effects?

MNT also spoke with Dr. Mir Ali, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, about this study.

He found the results unsurprising because one of the mechanisms of the GLP-1 agonists is to slow gastrointestinal tract emptying, which may also affect a person’s ability to use this type of medication.

“So it’s not that far a stretch to see how some people may be more sensitive to that. If patients have some indication that they may have poor stomach emptying or other intestinal symptoms, then we may steer them away from GLP-1 agonists and there are other options available,” he said.

The key to sustainable weight loss

For the next steps in research on this type of research, Dr. Bailony said he would like to see more controlled studies that account for variables like smoking and gender differences, which can influence the outcomes.

“It would be valuable to have matched cohorts for a more apples-to-apples comparison,” he continued.

“Also, it’s essential to communicate the results in terms of both relative and absolute risks, helping patients and healthcare professionals alike to make informed decisions. As always, the safety and well-being of our patients are paramount, so continuous monitoring and research into these medications are essential,” he said.

Dr. Ali also said for anyone looking to lose weight, no matter the health prevention aid they try — including medications, surgery, and counseling — the main goal is to help a person change to a healthier lifestyle.

“Nothing works if the patient doesn’t really make an effort to change their behavior. And so the concern is even with medications — they’ll help them lose weight and they may lose weight while they’re on the medications, [but without] long-term changes, when they stop the medication they can regain the weight. So, the goal is to make healthy long-term changes that will help keep the weight off.”
— Dr. Mir Ali

Source: Read Full Article