Clinical trial results and spontaneous postmarketing reports of pancreatitis have prompted the addition of label warnings and precautions possibly associating this condition with GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors.
1,2 However, patients with T2DM frequently have risk factors for pancreatitis (eg, hypertriglyceridemia, obesity, advancing age) and receive medications associated with drug-induced pancreatitis, confounding assessment of the relationship between individual agents, T2DM, and the risk of pancreatitis. For example, analysis of a claims database indicated that patients with T2DM have a 2.8-fold greater risk of acute pancreatitis and a 1.9-fold greater risk of biliary disease compared with those of patients without diabetes mellitus.
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In addition, analysis of a large commercial health insurance database revealed no increased risk of acute pancreatitis associated with exenatide or sitagliptin compared with metformin or glyburide.
9 Furthermore, review of preclinical and clinical data of the use of sitagliptin suggests no increased risk of pancreatitis in patients who were given that DPP-4 inhibitor.
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To our knowledge, neither GLP-1 receptor agonists nor DPP-4 inhibitors have been studied in patients with pancreatitis. Thus, these agents should not be used in individuals with pancreatitis or in those in whom a history of pancreatitis is suspected. Nonetheless, it is prudent to discuss current warnings about pancreatitis risks with patients to ensure an informed decision is made about initiating treatment. This counseling may also improve adherence to regimens, countering the influence of misinformation and nonmedical reports on patients' decision making.
Patients who initiate use of a GLP-1 receptor agonist or a DPP-4 inhibitor should be questioned about pancreatitis during assessments of their medical histories. There is no evidence that baseline laboratory tests of lipase and amylase levels are necessary in patients who initiate incretin-related therapy. Other antidiabetic agents, such as oral medications or insulin, should be considered in patients at risk for pancreatitis, including patients with a history of pancreatitis, a history of alcohol abuse, or current gallstones. If pancreatitis is suspected, any GLP-1 receptor agonist or DPP-4 inhibitor should be discontinued, and these agents should not be restarted if pancreatitis is confirmed.
An increased incidence of thyroid C-cell tumors was observed with liraglutide administration in rodents, but not in humans.
2 The liraglutide label includes a black box warning of thyroid C-cell cancer risk, noting that “human relevance could not be determined by clinical or nonclinical studies.”
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