I read this article a while back:
www.cnn.com/2023/07/25/health/weight-loss-diabetes-drugs-gastroparesis/index.htmlThey took blockbuster drugs for weight loss and diabetes. Now their stomachs are paralyzed
By Brenda Goodman, CNN
Updated 3:27 PM EDT, Tue July 25, 2023
Joanie Knight has a message for anyone considering drugs like Ozempic or Wegovy, which have become popular for the dramatic weight loss they can help people achieve.
“I wish I never touched it. I wish I’d never heard of it in my life,” said Knight, 37, of Angie, Louisiana. “This medicine made my life hell. So much hell. It has cost me money. It cost me a lot of stress; it cost me days and nights and trips with my family. It’s cost me a lot, and it’s not worth it. The price is too high.”
Brenda Allen, 42, of Dallas feels the same way. Her doctor prescribed Wegovy for weight loss.
“And even now, being off the medication for almost a year, I’m still having a lot of problems,” Allen said. She said she was at urgent care recently after vomiting so much that she became dehydrated.
Emily Wright, 38, a teacher in Toronto, started taking Ozempic in 2018. Over a year, she said, she lost 80 pounds, which she’s been able to keep off. But Wright said she now vomits so frequently that she had to take a leave of absence from her job.
“I’ve almost been off Ozempic for a year, but I’m still not back to my normal,” Wright said.
The diabetes drug Ozempic, and its sister drug for weight loss, Wegovy, utilize the same medication, semaglutide. These and other drugs in this family, which includes medications like tirzepatide and liraglutide, work by mimicking a hormone that’s naturally made by the body, GLP-1. One of the roles of GLP-1 is to slow the passage of food through the stomach, which helps people feel fuller longer.
If the stomach slows down too much, however, that can cause problems.
Knight and Wright have been diagnosed with severe gastroparesis, or stomach paralysis, which their doctors think may have resulted from or been exacerbated by the medication they were taking, Ozempic.
Wright said she has also been diagnosed with cyclic vomiting syndrome, which causes her to throw up multiple times a day.
Allen doesn’t have a diagnosis for her stomach problems but said they started only after she was encouraged by her doctor to take Wegovy to lose weight. She is managing her ongoing nausea and vomiting with a medication called Zofran and prescription probiotics while she waits for more tests in October — the first available appointments she could get with specialists.
Doctors say that more cases like these are coming to light as the popularity of the drugs soared. The US Food and Drug Administration said it has received reports of people on the drugs experiencing stomach paralysis that sometimes has not resolved by the time it’s reported.
And last month, the American Society of Anesthesiologists warned that patients should stop these medications a week before surgery because they can increase the risk that people will regurgitate food during an operation, even if they’ve fasted as directed. Vomiting under anesthesia sometimes causes food and stomach acid to get into the lungs, which can cause pneumonia and other problems after surgery.
So far, extreme and unrelenting cases like these are believed to be rare, and they may be a result of the drug unmasking or worsening an existing “slow stomach.” Doctors say people can have a silent condition called delayed gastric emptying and not know it. There’s nothing on the drugs’ labels that specifically cautions that gastroparesis may occur.
n response to CNN’s request for comment, Novo Nordisk, maker of Ozempic and Wegovy, pointed out that drugs in this class have been used for 15 years to treat diabetes and for eight years to treat obesity, and they have been extensively studied in the real world and in 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,” the statement said.
Gastroparesis can have many causes, including diabetes, which is a reason many people are on these drugs in the first place. Women are known to be at higher risk for the condition, too. In more than half of cases of gastroparesis, doctors are unable to find a cause.
“They may just be really unlucky,” said Dr. Michael Camilleri, a gastroenterologist at the Mayo Clinic, said of the people who shared their cases with CNN.
On the other hand, this is how the drugs work, although not many doctors or patients understand this or the problems that may follow, he said.
Camilleri received a grant from the National Institutes of Health to study how one of the first GLP-1 agonists, a drug called liraglutide, affects stomach function.
He recruited 40 obese adults and randomly assigned them to take increasing doses of liraglutide or a placebo, which had no active ingredients.
After five weeks, he had people in the study eat a meal laced with a radioactive tracer so he could see how long food stayed in their stomachs. People taking liraglutide had dramatically slowed digestion compared with those on the placebo; it took about 70 minutes for half the food they ate to leave their stomachs, compared with just four minutes in the placebo group. And that was just the average delay: In some patients on liraglutide, the time it took for half the meal to leave their stomachs was 151 minutes, or more than two and a half hours.
Camilleri said the group taking liraglutide lost weight, and the bigger the delay in food leaving the stomach, the more weight people seemed to lose.
Fortunately, people in the study seemed to adjust to the medication over time. After 16 weeks, people in the group taking liraglutide were clearing about half the food they ate from their stomachs in about 30 minutes, as opposed to seven minutes in the placebo group. Symptoms of nausea and vomiting seemed to ease, too.
“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.”
‘How am I throwing up this much?’
Joanie Knight remembers exactly what she ate on her birthday in 2021. She ordered chicken fajitas at one of her favorite restaurants. She ate three skinny French fries and two or three pieces of chicken and then felt panic set in when she couldn’t swallow the food.
“It felt like it was stuck in my throat,” said Knight, who had been taking Ozempic for two years at that point and was already eating very little every day as a result. Her birthday dinner triggered a bout of violent vomiting.
“I thought, ‘I hadn’t eaten. How am I throwing up this much?’ ” she said.
She went to see a gastroenterologist, a doctor who specializes in stomach problems. They put a tube with a camera down her throat and into her stomach to see what the issue might be.
“They said, ‘your stomach is full of food,’ ” she said.
Normally, less than 10% of the food will be left in the stomach four hours after a meal. When that climbs to between 10% and 15%, it’s considered mild gastroparesis. Moderate gastroparesis is when 15% to 35% of food is left. Severe gastroparesis is anything over 35% after four hours.
A gastric emptying study — a test that measures how food moves through the stomach — put Knight in the severe category. She said she stayed nauseated all the time, no matter how little she ate, and took a prescription anti-nausea medication “like it was candy.”
Still, doctors didn’t connect her stomach problems to the Ozempic she was taking. Although the prescription information for the drug warns of nausea and vomiting, it mentions only that the drug causes a delay in stomach emptying as a warning that it might affect the absorption of other medications. It was almost four more months until a specialist took her off the medication.
Emily Wright, the teacher from Toronto, said Ozempic helped her shed about 80 pounds in one year, and she continued to take it to help manage her blood sugar, but she always felt sick. She said she vomited every day but kind of got used to it: She would wake up and throw up, and then her day would get better.
In clinical trials, nearly half of people, 44%, who took Wegovy reported nausea, and almost 1 in 4 reported vomiting; both are common symptoms of gastroparesis.
In the clinical trials for Ozempic, which is the same medication as Wegovy but given at a lower dose, 1 in 5 people reported nausea and 1 in 10 reported vomiting.
In September 2020, Wright had to be hospitalized for dehydration related to the vomiting, and that prompted her to push her doctors for more answers. A gastric-emptying study showed that she had gastroparesis. Her doctors put her on two more medications to try to help her manage her symptoms but didn’t take her off the Ozempic because they didn’t suspect it was contributing.
Diabetes can also cause gastroparesis, but that typically happens only in people who have had the disease for at least a decade and have chronically high blood sugars that have damaged the nerves that control the stomach.
Both Knight and Wright say their doctors dismissed that possibility in their cases. “Everybody said there’s no way it’s diabetes,” said Wright, who had been diagnosed with diabetes for only five years when she developed gastroparesis.
In September 2022, her vomiting got much worse. Standing in front of her classroom, Wright said, she began having burps that smelled so strongly of sulfur and rotten eggs that the kids began to comment on it. “What is that? Where is it coming from?” they asked.
Then, instead of just vomiting the food she’d recently eaten, Wright noticed that she was throwing up food she’d eaten three or four days prior.
Another gastric emptying test showed her condition had deteriorated.
“Then the GI doctor said, ‘Well, I’ve been seeing a lot of clients coming in with full stomachs on endoscopy who are on Ozempic. So let’s try taking you off the Ozempic,’ ” Wright said.
Both Knight and Wright said they got some relief after coming off the medication, but their problems continued.
Now, Wright said, instead of throwing up a meal she ate several days ago, she mostly vomits food she has eaten recently.
For people with gastroparesis — from any cause — these stories are the norm. It takes a steep mental and physical toll on people who live with it.
Knight eventually had stomach bypass surgery. It’s similar to the technique used for weight loss, but it can also be a treatment for severe cases of gastroparesis. She said it has allowed her to eat some of her favorite foods again, like a few bites of pizza or chicken.
“Previously, I was on an extreme amount of vitamins because I wasn’t eating. Now I can eat enough that I’m not malnourished,” Knight said.
Wright said she’s just hoping her condition will improve with medications and time.
“We don’t know when we’re gonna get better. I think that’s the hardest part,” she said. “Like if you could give me like a year or two years, I would have something to hope for.”
Weighing benefits and risks
Drug regulators say they have received reports of stomach paralysis among patients taking GLP-1 agonist drugs.
“The FDA 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 agency said in a statement to CNN.
The reports have been submitted through the agency’s publicly accessible adverse events tracking system, and the FDA said there’s not always enough information in those reports to properly evaluate them.
The FDA said it has been unable to determine whether the medications were the cause or if the gastroparesis may have been caused by a different 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,” the agency said.
Asked whether doctors and patients should be warned about the risk for people who are know to have slow digestion to begin with, the FDA said the benefits of the medication may still outweigh its risks, even for this group.
“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,” the agency said.
The FDA said people with gastroparesis weren’t excluded from clinical trials of these medications, and the benefits for diabetes and weight management “may outweigh the risks in some patients with gastroparesis or delayed gastric emptying.”
Doctors who are experts in treating gastroparesis say they’re hearing more stories like these as greater numbers of people try the drugs.
“Gastroparesis or delayed gastric emptying from the GLP-1 agonists definitely does happen,” said Dr. Linda Nguyen, who specializes in the treatment of this condition at Stanford University.
What seems to be unusual about cases like Wright’s and Knight’s, Nguyen said, is that they didn’t improve after they stopped taking the medication.
“In my experience, when you stop the GLP-1 agonist, the gastric emptying improves, and it gets better,” said Nguyen, who is also a spokesperson for the American Gastroenterological Association.
Concern for surgery
Anesthesiologists say there are real hazards involved with stomach paralysis on these medications, and doctors and patients need more information about the risks.
Dr. Renuka George, fellowship director of regional anesthesiology at the Medical University of South Carolina, recently tweeted a photo of the stomach contents suctioned from a patient who had fasted as directed but was taking a GLP-1 agonist for diabetes. The stomach, she said, was basically full, even though the person had followed all the surgical prep instructions to the letter.
George explained that this is a cautionary tale.
“This has become more, I guess, front and center for anesthesiologists, simply because aspiration is a big concern,” she said.
George explained that the stomach and esophagus can handle the acidic digestive juices that mix with food. Lungs can’t.
“Lung tissue is fragile and precious,” George 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.”
She said that as more and more people take these medications, with little information about the stomach slowdown that comes with them, they may not know to tell their doctors.
“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?” she said. “So that becomes a problem because they’re not fasted appropriately.”
The American Society of Anesthesiologists is advising doctors to have patients stop these medications for one week prior to surgery to prevent aspiration, but President Dr. Michael Champeau said they aren’t sure what the right amount of time to fast or stop the drug would be.
“When we issued this guidance, we issued it on very limited scientific evidence,” Champeau said. These kinds of studies — on the delay in stomach emptying — just haven’t been done, he said.
He said their experts felt that stopping it one week in advance, for people taking it weekly, would be reasonable in the near term.
George said she was aware of ongoing studies to try to learn more about this complication.
“There’s a lot of research underway. I have a feeling that we’re going to see a lot of publications in the next few years regarding this,” she said.
Until more is known, George said, people need to be open with all their doctors about taking any drugs.
Knight, the gastroparesis patient in Louisiana, said people need to carefully consider the risks.
“I accepted that the medicine was working for me. I had a major side effect from it that altered my life course. Now I feel like my best option is to try to warn people whenever I can,” she said.
Nguyen, the Stanford doctor, said patients need to pay attention to the side effects. If you vomit once or twice, that might be normal, but persistent vomiting is not.
“They should be evaluated. Consider reducing the dose or stopping the medication,” she said.
“If your vomiting is affecting your hydration or you are having to take other medications to treat the side effects of this medication, then I think it’s time to reconsider.”
