March 6, 2013
GLP-1 Therapies Double Risk for Severe Pancreatitis in Patients With Diabetes

Baltimore—Glucagon-like peptide-1-based therapies (GLP-1) double the risk of hospitalization for pancreatitis compared to other drugs prescribed for blood sugar control in patients with diabetes, according to a new study.

Sitagliptin and exenatide, marketed as Januvia and Byetta, respectively, appear to contribute to the formation of lesions in the pancreas and the proliferation of ducts in the organ, resulting in greater risk of inflammation, according to Johns Hopkins University researchers. Their report was published online by JAMA Internal Medicine.

Pancreatitis has been suspected of being a side effect to the use of GLP-1, the newest drug class approved for blood sugar control, and the FDA knew the risk at the time of approval. This is the first study to quantify the risks in humans, however, taking into account factors such as gallstones, obesity, and heavy alcohol use.

“These agents are used by millions of Americans with diabetes. These new diabetes drugs are very effective in lowering blood glucose,” according to study leader Sonal Singh, MD, MPH. “However, important safety findings may not have been fully explored and some side effects such as acute pancreatitis don't appear until widespread use after approval.”

Pharmacists and other health professionals are urged to inform patients about symptoms of pancreatitis—nausea, persistent vomiting, and abdominal pain—and warn them to seek treatment immediately if any of those symptoms occur.

For the study, researchers used data from seven BlueCross BlueShield health insurance plans. First identifying 1,269 beneficiaries with type 2 diabetes who filled at least one prescription for any drug to treat the disease between 2005 and 2008, those were matched against 1,269 patients with type 2 diabetes who had not filled a prescription. Then, controlling for the other known pancreatitis risk factors, researchers determined that patients using one of the GLP-1 therapies were twice as likely to be hospitalized with pancreatitis within 60 days of therapy inception, compared to those taking a different medication.

“After adjusting for available confounders and metformin hydrochloride use, current use of GLP-1–based therapies within 30 days (adjusted odds ratio, 2.24 [95% CI, 1.36-3.68]) and recent use past 30 days and less than 2 years (2.01 [1.37-3.18]) were associated with significantly increased odds of acute pancreatitis relative to the odds in nonusers,” the authors write.

In the study group, a majority of whom were male with an average age of 54 years old, pancreatitis cases were significantly more likely to be found in those with hypertriglyceridemia (12.92% vs. 8.35%), alcohol use (3.23% vs. 0.24%), gallstones (9.06% vs. 1.34), tobacco use (16.39% vs. 5.52%), obesity (19.62% vs. 9.77%), biliary and pancreatic cancer (2.84% vs. 0%), cystic fibrosis (0.79% vs. 0%), and any neoplasm (29.94% vs. 18.05%).

The authors note that because of the role of the pancreas in diabetes, patients with diabetes are already at an increased risk for pancreatitis.

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