Risk Factors IDd for Acute Pancreatitis From Weight-Loss Drugs

CHARLOTTE, NC — Several factors appear to influence the risk for acute pancreatitis among patients who start taking glucagon-like peptide (GLP-1) receptor agonist medications for weight management, a new study has found.

Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.

On the other hand, a higher body mass index (BMI) — 36 kg/m2 or higher — appeared to protect people against developing the condition.

“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on 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 (ACG) 2022 Annual Scientific Meeting in Charlotte, North Carolina, being held in person and virtually.

Popularity Comes at a Price

The US Food and Drug Administration has approved two GLP-1s for weight management — liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat 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 an ongoing shortage of the medication in the United States.

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

Postlethwaite and colleagues performed a retrospective, single-center study of 2245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m2.

The study only included patients starting GLP-1s for treating obesity, not for diabetes.

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

A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval [CI], 1.04 – 3.96; P = .04).

Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18 – 4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70 – 6.50; P < .001).

In contrast, researchers found those with a BMI of 36-40 kg/m2 were 88% less likely to develop acute pancreatitis (95% CI, 0.07 – 0.67; P = .007) compared with patients with a BMI of ≤ 30 kg/m2. Patients with a BMI of greater than 40 kg/m2 had a 73% lower risk (95% CI, 0.10 – 0.73; P = .01).

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

Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”

“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Postlethwaite said.

“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.

Larger Studies Needed

The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health in Charlotte, North Carolina, who was not affiliated with the research.

However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.

“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Moshiree said.

Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.

Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, 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.

American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting: ACG Newsworthy Abstract 18. Presented October 24, 2022.

The study was independently supported. Postlethwaite and Moshiree report no relevant financial relationships.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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