(CNN) — Injectable medications to treat diabetes and obesity increase the risk of a rare but serious side effect: stomach paralysis, according to new data on their real-world use.
At least three new studies based on large collections of patient records show that the risk of being diagnosed with stomach paralysis, or gastroparesis, is higher in people who take GLP-1 agonists than in those who do not take them.
The studies have not been reviewed by outside experts or published in medical journals, so the data are considered preliminary. Two of them were presented this Saturday at the Digestive Disease Week 2024 medical congress, held in Washington; the third is scheduled to be presented this Monday.
Injectable medications called GLP-1 agonists are in high demand because they have been shown to be very effective for weight loss. In clinical trials, some of the most powerful ones, such as Wegovy and Zepbound, helped lose at least 10% of initial weight. Studies also concluded that they are beneficial for both the heart and waistline. According to Novo Nordisk, 25,000 people start taking Wegovy each week in the United States alone.
The drugs curb appetite by slowing the passage of food through the stomach. They also help the body release more insulin and send signals to the brain that reduce cravings.
In some people, however, these medications can also cause unpleasant to severe episodes of vomiting, which may require medical attention. They can also slow down the stomach so much that medical tests reveal a condition called gastroparesis.
Most of the time, according to doctors, gastroparesis improves after stopping the medication. However, some people claim that their condition did not improve even months after stopping the drug, with life-altering consequences.
Gastroparesis risk measurement
In the new studies, the risk of gastroparesis appears to be low but constant. Compared with similar people who were not taking GLP-1 medications, those who were taking them had an approximately 50% higher risk of being diagnosed with the disease.
A study led by researchers at University Hospitals Cleveland used records from the TriNetX database, which includes millions of medical records from 80 healthcare organizations. The analysis focused on adults who were obese, with a body mass index greater than 30, but who did not have a diagnosis of diabetes nor had they been diagnosed with gastroparesis or pancreatitis at least six months before starting GLP-1 medication. The records of more than 286,000 patients were included in the study.
Diabetes itself can also increase the risk of gastroparesis, especially if a person’s blood sugar has not been well controlled for a long period of time.
Among people prescribed a GLP-1 weight loss drug—such as semaglutide (brand names Ozempic and Wegovy), exenatide (Byetta), and liraglutide (Victoza)—10 in 10,000, or 0.1 % were diagnosed with gastroparesis at least six months later. In comparison, 4 in 10,000 people, or 0.04%, who were matched in the database by age, sex, ethnicity and other factors, but who were not taking a GLP-1 medication, developed the disease.
The statistically significant difference was equivalent to a 52% increase in the risk of stomach paralysis while taking a GLP-1 medication.
A second study, led by researchers at the University of Kansas, also used records from the TriNetX research network database. It included patients who were prescribed GLP-1 medications for diabetes or obesity between December 2021 and November 2022, and compared them to people who had diabetes or obesity and had been seen by a doctor during the same time period. , but who had not been prescribed a GLP-1 medication. The records of almost 300,000 patients were included in the study.
Compared to those who did not take GLP-1 medication, those who did were 66% more likely to be diagnosed with gastroparesis. This study revealed that 0.53% of patients taking GLP-1 drugs were diagnosed with stomach paralysis, that is, approximately 1 case of gastroparesis for every 200 people taking the drugs.
People taking GLP-1 medications were also more likely to experience nausea and vomiting or gastroesophageal reflux disease (GERD) and to be prescribed a proton pump inhibitor. They were also more likely to have their gallbladder removed and to suffer from drug-induced pancreatitis.
“While these drugs work and should be used for the right reasons, we want to warn everyone that if you decide to start taking them, you should be prepared for a 30 percent chance of experiencing gastrointestinal side effects, and in that case, it is possible should be stopped,” said study author Dr. Prateek Sharma, a professor of medicine at the University of Kansas School of Medicine.
Some medication side effects may also lessen over time, as people get used to their doses. This is one of the reasons why doctors start with a low dose of the drug and increase it over time.
Sharma noted that the study included people with diabetes in both the group taking the GLP-1 drugs and the comparison group, and yet a higher incidence of stomach paralysis was seen in those taking the drugs, suggesting that Diabetes alone was not the cause of the increased risk.
“The drug was the only thing that differed between the two groups,” he says.
“And we showed that all gastrointestinal side effects or symptoms (nausea, vomiting, and gastroparesis) were significantly higher in those taking GLP-1 than in controls,” said Sharma, who is also president-elect of the American Society of Gastrointestinal Endoscopy.
Were any adverse effects missed in clinical trials?
Although these drugs have been studied extensively, Sharma believes it is possible that gastroparesis is rare enough that it did not appear in clinical trials of the drugs because they did not include enough patients.
“You need hundreds of thousands of patients to reach these conclusions, but that’s why I think these database studies are much more important,” Sharma says.
According to Dr. Michael Camilleri, a gastroenterologist and researcher at the Mayo Clinic who has studied gastroparesis with the GLP-1 drug liraglutide, another reason it may have been overlooked in clinical trials is the way researchers typically perform tests to detect it.
“It is very important, if you are going to study the problem of gastric emptying, to observe gastric emptying of solids, not liquids” from the stomach, Camilleri said. Liquids pass through the stomach more quickly than solids.
“When pharmaceutical companies did the evaluation of the effects of this class of medications on gastric emptying, they usually used a method that evaluates the emptying of fluids from the stomach,” he said.
It is called an acetaminophen absorption test, and it is often used because it is faster and less expensive than a gastric emptying study with scintigraphy, which uses a radioactive tracer to see how much solid food remains in the stomach hours after a meal.
Paracetamol is absorbed through the stomach and fluids carry it into the bloodstream. Measuring how quickly paracetamol appears in the blood can give an idea of the rate at which liquids pass through the stomach, but not solids. Camilleri and other experts say that acetaminophen absorption is not an adequate test to detect gastroparesis with GLP-1 medications.
Camilleri co-authored a third study presented Monday at Digestive Diseases Week, which looked at gastroparesis with GLP-1 medications.
That study examined the records of nearly 80,000 patients who had been prescribed a GLP-1 medication by doctors at the Mayo Clinic Health System. The researchers focused on a subgroup of 839 people who had had symptoms of gastroparesis and who had undergone a gold standard test for the disease: a procedure called gastric emptying scan.
About a third of that group, 241 people, had food in their stomachs four hours after eating a test meal, meaning they met the criteria for having gastroparesis.
However, the study did not calculate the difference in the risk of gastroparesis between people who took the drugs and those who did not.
Camilleri noted that the risk of gastroparesis is likely underestimated in these studies because not everyone who had symptoms would have ultimately undergone the testing needed to diagnose it.
In the Mayo Clinic study, women and people who also reported constipation with GLP-1 medications were more likely to be diagnosed with gastroparesis.
Camilleri noted that constipation may be an indication that people will have problems with gastroparesis on a GLP-1 medication, but that there are still many questions to be answered.
“For people who suffer from this complication, it is extremely serious,” he said.