FDA said it has received reports of some patients taking semaglutide — a drug used to treat diabetes and weight loss — experiencing severe gastroparesis, or "stomach paralysis," in which digestion of food slows significantly, potentially causing severe vomiting and nausea, Brenda Goodman reports for CNN.
Semaglutide is a drug that mimics a hormone called glucagon-like peptide-1 (GLP-1) to target areas of the brain that regulate appetite and food intake. Semaglutide, which is manufactured by Novo Nordisk, is sold under the brand name Ozempic for diabetes and Wegovy for obesity.
Some common side effects of semaglutide include nausea, stomach pain, constipation, diarrhea, and vomiting. However, other side effects, including some that have resulted in hospitalizations, have also been reported.
According to FDA, the agency "has received reports of gastroparesis with semaglutide and liraglutide, some of which documented the adverse event as not recovered after discontinuation of the respective product at the time of the report."
The reports have been submitted through FDA's publicly accessible adverse events tracking system, and the agency said it has been unable to determine whether the medications caused the gastroparesis or if the condition was caused by a separate issue.
"Gastroparesis can be a complication of diabetes that is related to long-standing or poorly controlled disease, further complicating the ability to determine what role the drugs played in the reported events," FDA said.
Gastroparesis has a number of causes, Goodman reports, including diabetes. However, in more than half of gastroparesis cases, doctors have been unable to find a cause.
Patients taking semaglutide and experiencing gastroparesis "may just be really unlucky," said Michael Camilleri, a gastroenterologist at the Mayo Clinic.
Camilleri received an NIH grant to study how liraglutide, one of the first GLP-1 agonist drugs, affected stomach function.
To do this, Camilleri recruited 40 obese adults and randomly assigned them to either take increasing doses of liraglutide or a placebo. After five weeks, Camilleri then had the participants eat a meal with a radioactive tracer so he could determine how long food stayed in their stomachs.
Camilleri found that people taking the liraglutide saw dramatically slowed digestion. On average, it took 70 minutes for half the food in those participants to leave their stomach compared to four minutes in the placebo group, and in some participants taking liraglutide, it took as long as 151 minutes for half the food to leave their stomach.
According to Camilleri, those taking liraglutide lost weight, and the larger the delay in food leaving the stomach, the more weight people lost. He also found that, after 16 weeks, people who took liraglutide saw their stomachs clear half the food they ate in about 30 minutes compared to seven minutes in the placebo group, and symptoms of nausea and vomiting eased as well.
"Unfortunately, there have not been these types of robust studies, and so the whole idea that this class of medications actually delays gastric emptying is not as well recognized," Camilleri said. "It is conceivable that some patients may have borderline slow gastric emptying and starting one of the GLP-1 agonists may precipitate a full-blown gastroparesis."
Linda Nguyen, who specializes in the treatment of gastroparesis at Stanford University, said that "gastroparesis or delayed gastric emptying from the GLP-1 agonists definitely does happen," but the fact that some patients aren't getting better after they stop taking the medication is odd.
"In my experience, when you stop the GLP-1 agonist, the gastric emptying improves, and it gets better," Nguyen said.
When asked whether doctors and patients should be warned about the risk of gastroparesis in patients with slow digestion, FDA noted the benefits of semaglutide may still outweigh the risks.
"Regulations pertaining to drug labeling state that a drug should be contraindicated only in those clinical situations for which the risk from use clearly outweighs any possible therapeutic benefit. Only known hazards, and not theoretical possibilities, can be the basis for a contraindication," FDA said.
The agency noted that patients with gastroparesis weren't excluded from clinical trials for the medications, and the benefits of treatment for diabetes and weight management "may outweigh the risks in some patients with gastroparesis or delayed gastric emptying."
In a statement, Novo Nordisk noted that GLP-1 agonists have been used for 15 years to treat diabetes and for eight years to treat obesity and have been extensively studied in real world and clinical trials.
"Gastrointestinal (GI) events are well-known side effects of the GLP-1 class. For semaglutide, the majority of GI side effects are mild to moderate in severity and of short duration. GLP-1's are known to cause a delay in gastric emptying, as noted in the label of each of our GLP-1 RA medications. Symptoms of delayed gastric emptying, nausea and vomiting are listed as side effects," Novo Nordisk said.
Some doctors have expressed concerns about the potential of gastroparesis causing problems during surgery. Last month, the American Society of Anesthesiologists (ASA) warned that patients should stop taking GLP-1 agonists a week before surgery due to their risk that people may regurgitate food during an operation, which can cause food and stomach acid to get into the lungs.
Renuka George, fellowship director of regional anesthesiology at the Medical University of South Carolina, recently tweeted a photo of the stomach contents of a patient who had fasted like they were supposed to before surgery, but was taking a GLP-1 agonist for their diabetes. George said the stomach was essentially full, despite the patient following all surgical prep instructions perfectly.
"This has become more, I guess, front and center for anesthesiologists, simply because aspiration is a big concern," George said.
According to George, the stomach and esophagus are able to handle the acidic juices that mix with food in the stomach. "Lung tissue is fragile and precious," she said. "If anything goes into the lungs, at best, it's a cough; at worst, you end up on a ventilator for an extended period of time."
As more patients take GLP-1 agonists without much information about the potential for gastroparesis, they may not know they need to tell their doctors, George said.
"The big concern is if we have patients that aren’t aware of this and don't tell their anesthesiologists because not everybody wants to advertise that they're on a weight loss drug, right?" George said. "So that becomes a problem because they're not fasted appropriately."
ASA President Michael Champeau said the association isn't sure exactly what the right amount of fasting time is for people taking GLP-1 agonists, but felt that stopping one week in advance would be reasonable in the short-term.
Until more is known about these drugs, George said patients need to be open with all of their doctors about taking any drugs.
"There's a lot of research underway," George said. "I have a feeling that we're going to see a lot of publications in the next few years regarding this." (Goodman, CNN, 7/25)
Demand — and concern — is growing for the newest generation of weight loss drugs, and leaders have many questions about protocol, supply, and coverage of these drugs, as well as the consequences of patients using them for their unintended purpose. Radio Advisory's Rachel Woods walked through these questions with experts Kara Marlatt, Gaby Marmolejos, and Chloe Bakst and discussed the potential future of weight management in U.S. healthcare. Read a lightly edited excerpt from the interview and listen to the episode below.
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