Alicia Gallegos

December 19, 2024

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Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville, Virginia.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.Catherine Varney, DO

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University in Morgantown, West Virginia. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs, she said.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.Anila Chadha, MD

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different, she said.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history, she said.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.Laura Davisson, MD, MPH

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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