Identified risk factors for acute pancreatitis caused by weight-loss medications

Several factors influence the risk of developing acute pancreatitis in patients who start glucagon-like peptide (GLP-1) receptor agonist drugs for weight control, a new study has found.

Type 2 diabetes, chronic kidney disease, and tobacco smoking have been linked to an increased risk of developing acute pancreatitis, researchers report.

On the other hand, a higher body mass index (BMI) - 36 kg/m or higher - has been shown to protect people from developing the disease.

"As this class of drugs becomes increasingly popular in the United States, it's important for physicians to know which patients have a higher or lower risk of developing acute pancreatitis after starting them," said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center in Dallas.

The findings were presented at the American College of Gastroenterology's (ACG) 2022 Annual Scientific Meeting in Charlotte, North Carolina, which was held in person and virtually.

Popularity has a price

The FDA approved two GLP-1 drugs for weight control, liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They act on parts of the brain that control food intake and appetite. Other GLP-1s approved for the treatment of type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).

The demand for Wegovy has been so great that there is a constant shortage of the drug in the United States.

Although GLP-1 shows a favorable side-effect profile compared with other types of obesity drugs, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.

Postlethwaite and colleagues conducted a retrospective, single-center study of 2,245 patients who participated in the Weight Wellness program at an academic medical center from 2015 to 2019. The mean age of the patients was approximately 50 years, 81% were female, and the mean BMI of all patients was 39.7 kg/month.

Only patients starting GLP-1 to treat obesity, not diabetes, were included in the study.

Of 2245 patients, 49 (2.2%) developed acute pancreatitis after starting GLP-1.

A history of type 2 diabetes increased the likelihood of acute pancreatitis by a factor of two (95% confidence interval [CI], 1.04 to 3.96; P = .04).

Chronic kidney disease stage 3 or higher increased risk 2.3-fold (95% CI, 1.18 to 4.55; P = .01) and tobacco use 3.3-fold (95% CI, 1.70 to 6.50; P < .001).

In contrast, the researchers found that patients with a BMI of 36-40 kg/m had an 88% lower risk of developing acute pancreatitis (95% CI, 0.07 to 0.67; P = .007) compared with patients with a BMI ≤30 kg/m. Patients with a BMI greater than 40 kg/m had a 73% lower risk (95% CI, 0.10 to 0.73; P = .01).

Postlethwaite and colleagues found no association with age, gender, history of bariatric surgery, and acute pancreatitis.

Because a history of acute pancreatitis is not a risk factor, he advised physicians not to refuse to take these drugs for that reason, "especially given the significant glycemic, cardiovascular and weight-loss effects."

"We hope to be able to arm clinicians with factual data so they can stratify their patients' risk and determine who is at high risk of developing pancreatitis," Postlethwaite said.

"Hopefully, we can prevent some patients from developing pancreatitis, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to detect it early enough to prevent complications of acute pancreatitis," he added.

More research is needed

The study is "promising," said session co-moderator Baharak Moshiri, MD, a gastroenterologist at Atrium Health in Charlotte, North Carolina, who was not affiliated with the study.

However, because the study was retrospective and relatively small, its results need to be confirmed in larger prospective studies, she added.

"Because obesity is such a global problem, many patients are taking these GLP-1 agonists," Moshiri said.

Typically, these drugs are prescribed by endocrinologists, not gastroenterologists, she noted, and said gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects such as nausea and vomiting, which can occur due to delayed gastric emptying.

Postlethwaite noted that a limitation is the inability to estimate how much alcohol or tobacco people consumed. The relatively low proportion of people who developed acute pancreatitis during the study also means more research is needed, he added.

Going forward, Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl peptidase 4) inhibitors.

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