GLP-1 pancreatitis concerns justified

Study results have raised further concerns over a link between pancreatitis and the use of glucagon-like peptide-1 (GLP-1)-based therapies for patients with Type 2 diabetes.

The findings, published in JAMA Internal Medicine, show that patients taking sitagliptin and exenatide had double the risk for hospital admission for acute pancreatitis compared with Type 2 diabetes patients not taking these drugs.

The study included 1269 patients admitted to hospital with acute pancreatitis and 1269 control patients closely matched for age, gender, diabetes complications, and enrollment patterns.

Sonal Singh (Johns Hopkins University, Baltimore, Maryland, USA) and colleagues report that patients who were hospitalized with acute pancreatitis were more likely than controls to have hypertriglyceridemia (12.9 vs 8.4%), alcohol use (3.2 vs 0.2%), gallstones (9.1 vs 1.3%), tobacco abuse (16.4 vs 5.5%), obesity (19.6 vs 9.8%), biliary and pancreatic cancer (2.8 vs 0.0%), and cystic fibrosis (0.8 vs 0%).

However, after controlling for these factors, as well as metformin use, GLP-1 therapy use within the previous 30 days was still associated with a 2.24-fold increase in the odds for hospital admission for acute pancreatitis. Patients who had used GLP-1 agents in the past 2 years (but had stopped treatment at least 30 days earlier) were 2.01 times more likely to be admitted than nonusers.

Since the launch of GLP-1-based therapies, there have been numerous reports of acute pancreatitis among patients, and rodent models have supported this association. However, the authors say that previous population studies have lacked sufficient statistical power and failed to adequately control for confounders.

In a related commentary, Belinda Gier and Peter Butler, from the University of California, Los Angeles, USA, say that the findings are a warning that the drugs still have unknown effects, particularly on the risk for pancreatic cancer.

"Now that Singh and colleagues have brought clarity to the increased risk of pancreatitis with GLP-1-based therapy, the time has come to move forward and address the wider implications of this finding," they write.

The commentators add the research provides "a timely reminder that, despite large numbers of underpowered studies claiming the contrary from marketing companies, little is yet known about long-term adverse effects of the GLP-1 class of drugs on the exocrine pancreas."

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