Dallas—What factors make it more or less likely that patients initiating GLP-1 receptor agonist (GLP-1RA) therapy for weight loss will develop acute pancreatitis?

That was the question addressed on October 24, 2022, at the American College of Gastroenterology’s Annual Scientific Meeting in Charlotte, North Carolina.

“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,” stated presenter Robert Postlethwaite, MD, of the University of Texas Southwestern. “In particular, we only included patients being started on a GLP-1RA for the treatment of obesity, not for the treatment of diabetes.”

The analysis determined that a higher risk of developing acute pancreatitis was linked to:

• History of type 2 diabetes mellitus
• Tobacco use
• Advanced chronic kidney disease (CKD; stage III or greater).

“Notably, known clinical risk factors for acute pancreatitis including alcohol use, prior history of acute pancreatitis, and gallstone disease were not associated with an increased risk of acute pancreatitis after GLP-1RA initiation in this study,” Dr. Postlethwaite advised, adding, “In the future, clinicians can utilize this information to risk stratify their patients when prescribing GLP-1RAs. In turn, we can prevent the development of acute pancreatitis in high-risk individuals or at the least be more aware of its risk and be able to identify it early enough to prevent complications.”

The study uncovered no evidence that a prior history of acute pancreatitis increases the risk of developing a subsequent episode after being started on a GLP-1RA. “Therefore, clinicians should not withhold these medications for this reason,” Dr. Postlethwaite noted.

The background information in the study pointed out that GLP-1RAs have revolutionized the management of obesity and are widely prescribed for treating obesity and associated comorbidities, primarily type 2 diabetes mellitus (T2DM).

“Although GLP-1RAs demonstrate a favorable side effect profile compared to other types of anti-obesity medications, acute pancreatitis (AP) remains a serious and sometimes life-threatening adverse effect,” the authors wrote. “Unfortunately, there are a paucity of data regarding which patients may be at increased risk of developing AP from GLP-1RAs. The purpose of this study is to identify patient factors that impact the risk of AP after initiation of GLP-1RA treatment for obesity.”

In response, the study team performed a retrospective, single-center study in patients seen at an academic institution’s Weight Wellness program between January 1, 2015, and December 31, 2021. Patients beginning GLP-1RA therapy were stratified based on the development of acute pancreatitis.

Baseline patient characteristics, medical comorbidities, and surgical history were obtained from chart review for the 2,245 participants with an average age of 49.5 years. Most (80.5%) were female, and participants had an average BMI of 39.7 kg/m2. Of the 2,245 patients, 49 (2.2%) developed AP after starting a GLP-1RA.

The results indicated that a history of T2DM (adjusted odds ratio (aOR) 2; 95% CI, 1.04-3.96, P = .04), tobacco use (aOR 3.3; 95% CI, 1.70-6.50, P <.001), and advanced (stage III or greater) CKD (aOR 2.3; 95% CI, 1.18-4.55, P = .01) were associated with a higher risk of AP with GLP-1RA use.

Interestingly, the study found that a higher BMI appears to be protective against AP. “Compared to patients with a BMI ≤30 kg/m2, those with a BMI 36-40 and BMI >40 were associated with a lower risk of AP after GLP-1RA use with an aOR of 0.22 (95% CI, 0.07-0.67, P = .007) and 0.27 (95% CI, 0.10-0.73, P = .01), respectively,” according to the results. “There was no association between age, sex, history of bariatric surgery, or history of AP and the development of AP after GLP-1RA use.”

“Recognizing the predictive factors of GLP-1RA-associated AP can inform clinicians on risk stratification and symptom monitoring,” the authors stated.

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