Patients with type 2 diabetes at high risk for cardiovascular events had a lower risk for acute pancreatitis when taking liraglutide compared with patients taking placebo, according to recent research published in Diabetes Care.
William M. Steinberg, MD, from the George Washington University Medical Center, Washington, DC, and colleagues noted regulatory bodies in the United States and Europe have identified pancreatitis as a risk factor for patients taking incretion-based drugs, citing data from patients taking glucagon-like peptide 1 (GLP-1) receptor agonists.
“Due to the previous results and the lack of long-term data, pancreatitis continues to be of interest in studies of GLP-1 receptor agonists, particularly in studies where long-term safety data can be collected,” the researchers wrote. “Furthermore, serial amylase and lipase measurements have been suggested to predict the development of acute pancreatitis.”
A total of 9340 patients with type 2 diabetes in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial (LEADER; ClinicalTrials.gov identifier: NCT01179048) were randomly assigned to receive either 1.8 mg/d liraglutide or placebo during a mean 3.07-year treatment period (median observation time, 3.84 years) and 30-day follow-up. Patients were a mean age of 64.3 years and had diabetes for a mean duration of 12.9 years enrolled at 410 sites in 32 countries.
The primary outcome was designated as cardiovascular-associated mortality, nonfatal myocardial infarction, or nonfatal stroke. The study also included blinded adjudication of acute pancreatitis.
Patients in the liraglutide group showed a serum lipase increase of 28.0% and a 7.0% increase in amylase compared with patients in the placebo group. Adjudication confirmed 18 cases of acute pancreatitis in the liraglutide group (0.4%; 1.1 events per 1000 patient-years) and 23 cases in the placebo group (0.5%; 1.7 events per 1000 patient-years), with cases occurring at a minimum of 12 months after beginning treatment.
“Our results do not support the exclusion of patients with previous pancreatitis from treatment with GLP-1 receptor agonists in general terms and with liraglutide in particular,” the researchers noted. “Nevertheless, the study protocol did not call for an active investigation to characterize previous pancreatic or biliary structural or functional damage.”
Of 147 patients with a prior history of pancreatitis in the liraglutide group, 2 patients (1.4%) developed acute pancreatitis in the study; of 120 patients in the placebo group with a history of pancreatitis, 6 patients (5.0%) developed acute pancreatitis. The researchers noted that elevated levels of amylase and lipase in the liraglutide group were also not associated with future risk for acute pancreatitis (predictive value, <1%).
“The present analysis provides details on the blinded adjudication process that demonstrate sufficient data were available for either confirming or refuting the diagnosis of acute pancreatitis for those events that were adjudicated,” the researchers wrote. “These data also show that despite more suspected events sent for adjudication with liraglutide treatment (most likely due to lipase and amylase increases as well as abdominal pain) vs placebo, among those events not confirmed by adjudication, the extent of workup was similar between the 2 groups.”
Disclosures: This study was funded by Novo Nordisk. The researchers report financial relationships with various pharmaceutical companies.
Steinberg WM, Buse JB, Ghorbani MLM, et al. Amylase, lipase, and acute pancreatitis in people with type 2 diabetes treated with liraglutide: results from the LEADER randomized trial [published online May 5, 2017]. Diabetes Care. doi:10.2337/dc16-2747