Drugs Like Ozempic, Wegovy Linked to Greater Risk of Severe Gastrointestinal Side Effects

The social conversation surrounding weight loss drugs has continued to increase, but are there gastrointestinal side effects you should be talking about?

Glucagon-like peptide 1 (GLP-1) agonists, more commonly known by such brand names as Ozempic and Wegovy, are medications that have gained widespread attention, known for their ability to help people lose weight.

Although most of these drugs are intended for people with type 2 diabetes, many doctors also prescribe them for weight loss. (Wegovy, which has the same active ingredient as Ozempic, was approved for weight loss in 2021.)

Aside from the benefits associated with the drug, previous research has demonstrated gastrointestinal side effects among diabetic patients taking the medication, including biliary disease (diseases of the gallbladder and bile ducts), pancreatitis (inflammation of the pancreas), bowel obstruction, and gastroparesis (delayed emptying of the stomach contents into the small intestine).

“These medications work by activating receptors in the pancreas to enhance insulin release and decrease the release of another hormone, glucagon,” said Brooks Cash, MD, professor and chief of gastroenterology, hepatology, and nutrition at UTHealth Houston.

“They also decrease appetite though their action of slowing gastric emptying which,” he said, “along with effects in the central nervous system.”

While this is the reason the drugs result in successful weight loss, the function may also contribute to negative side effects.

The most common side effects of these drugs are gastrointestinal and include nausea, vomiting, bloating and fullness, Cash said, but other side effects have been reported, including potential long-term effects on the thyroid gland and rarely, pancreatitis.

In a new study, published earlier this month in JAMA, researchers decided to explore these adverse side effects associated with GLP-1 agonists.

The study’s results indicated that the use of GLP-1 agonists for weight loss was linked to a greater risk of pancreatitis, gastroparesis, and bowel obstruction, but not biliary disease.

“What was compelling is that our results confirm what people have been reporting recently in terms of the GI side effects with these drugs,” said study author Mahyar Etminan. “This information can help those who want to take these drugs for weight loss to make more informed decisions.”

What to Know About the Gastrointestinal Side Effects of Weight Loss Drugs

Before taking a new medication, it’s important to understand how possible side effects could impact your health.

“These drugs [like Ozempic, Wegovy] cause gastroparesis, which is advantageous for patients with diabetes to improve the match between glucose and insulin,” Caroline Korsten Messer, MD, an endocrinologist at Northwell Health, told Health. “However, the gastroparesis can also worsen nausea, reflux, and burping.”

The rapid weight loss associated with these medications causes an increased flux of cholesterol through the gallbladder, which can promote the growth of gallstones, Messer said. These stones can trigger pancreatitis.

While nausea and vomiting can occur in 10–50% of patients, Messer explained that severe side effects, like pancreatitis and gallstones, are rare. The risk of pancreatitis is approximately 0.001% and the risk of gallstones appears to be ~ 1%.

“The more serious adverse events such as pancreatitis and bowel obstruction are thought to be quite rare,” said Cash. “The current report does not provide incidence data for these adverse events so it is not possible to conclude how common they are with these medications.”

However, the conditions do appear to be uncommon in clinical practice.

Gastroparesis, which is the technical term for delayed gastric emptying, is a more common adverse effect and is expected based on the mechanism of action of these medications as well as the fact that they are most often used in patients with diabetes, which is one of the most important risk factors for gastroparesis, Cash explained.

Who Is Most at Risk for These Side Effects?

Not everyone taking a GLP-1 weight loss medication will experience side effects—people who are losing a more extreme amount of weight are at a higher risk.

“Patients experiencing greater amounts of weight loss are likely at higher risk,” said Messer. “It is also feasible that overweight women in their 40s are at greater risk since these are at-risk patients for gallstones in general.”

Regarding gastroparesis, patients with long-standing, poorly controlled diabetes are expected to be more at risk for exacerbation of gastroparesis symptoms such as nausea, vomiting, abdominal pain, and bloating, Cash said, because these patients are most at risk for gastroparesis in general.

While it’s not clear who may be more at risk for other adverse reactions from these drugs, Cash explained that patients with general health risk factors should consider how these additional side effects may impact their well-being.

This includes heavy alcohol use (which can, on its own, impact someone’s risk of pancreatitis), which should be carefully considered and counseled prior to starting these medications.

Assessing the Benefits and Potential Risks of Weight Loss Medication

Choosing whether or not to take a weight loss medication is a decision that must be made with the supervision of a healthcare professional.

“This is a decision that has to be individualized for each patient in consultation with their healthcare provider and highlights the need for additional research and understanding of how common, or rare, these reported adverse events actually are,” said Cash.

That being said, these medications are proven to work and can have a very positive impact.

“These medications are the only true longevity medications on the market,” Messer stated. “Their impact on physical and emotional health is undeniable.”

She explained that in addition to well-known cardiovascular benefits, the medications also potentially help maintain a variety of inflammatory conditions.

However, it’s important for people to know all of the pros and cons before taking the medication.

“Every decision we make as doctors is a calculated analysis of cost vs benefit,” said Messer. “The vast majority of the medical community stands behind the appropriate use of these medications.”

Cash agrees patients should be aware of the risks and benefits of any medication before they take it.

“Many medications that have been proven to improve health-related outcomes have potential side effects and these have to be weighed against potential risks,” he said. “These medications have proven themselves to be very important and helpful medications for many people but they do need to be used responsibly and with knowledge and understanding of potential downsides that may exist as well.”