Should you stop GLP-1 (Glucagon-like peptide-1) receptor agonists if lipase is elevated without active symptoms of pancreatitis?

From the Guidelines

Elevated lipase levels without symptoms of pancreatitis generally do not require discontinuation of GLP-1 receptor agonists, but it is crucial to monitor lipase levels regularly, especially during the first year of treatment, and educate patients on symptoms of pancreatitis that warrant immediate medical attention. The decision to continue or discontinue GLP-1 receptor agonists in the presence of elevated lipase levels without symptoms of pancreatitis should be based on the severity of the lipase elevation and the presence of any symptoms suggestive of pancreatitis.

According to the most recent and highest quality evidence available, if lipase elevation is mild to moderate (less than 3 times the upper limit of normal) and the patient is asymptomatic, continued use of medications like semaglutide, liraglutide, dulaglutide, or tirzepatide is typically acceptable with monitoring 1. However, if lipase levels exceed 3 times the upper limit of normal or if any symptoms of pancreatitis develop (such as severe abdominal pain radiating to the back, nausea, vomiting), the medication should be immediately discontinued and the patient evaluated for pancreatitis.

Key considerations include:

• Regular monitoring of lipase levels, particularly during the first year of treatment
• Patient education on symptoms of pancreatitis
• Immediate discontinuation of the medication if symptoms of pancreatitis develop or if lipase levels exceed 3 times the upper limit of normal
• The association between GLP-1 receptor agonists and pancreatic enzyme elevations, although asymptomatic elevations often do not progress to clinical pancreatitis 1

In clinical practice, the management of patients on GLP-1 receptor agonists with elevated lipase levels without symptoms of pancreatitis should prioritize careful monitoring and patient education, with a low threshold for discontinuing the medication if any concerns arise regarding pancreatitis. This approach balances the benefits of GLP-1 receptor agonists in managing type 2 diabetes and reducing cardiovascular risk with the need to minimize the risk of pancreatitis.

From the FDA Drug Label

In one adult glycemic control trial in renal impairment patients, a mean increase of 33% for lipase and 15% for amylase from baseline was observed for liraglutide injection-treated patients while placebo-treated patients had a mean decrease in lipase of 3% and a mean increase in amylase of 1% The clinical significance of elevations in lipase or amylase with liraglutide injection is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions (5. 2)].

The FDA drug label does not provide clear guidance on whether to stop GLP-1 receptor agonists if lipase is elevated without active symptoms of pancreatitis. However, it mentions that the clinical significance of elevations in lipase or amylase is unknown in the absence of other signs and symptoms of pancreatitis.

• Key points:
  • Elevations in lipase and amylase have been observed in patients treated with liraglutide injection.
  • The clinical significance of these elevations is unknown without other signs and symptoms of pancreatitis. Given the uncertainty and potential risk, a conservative approach would be to exercise caution and consider stopping GLP-1 receptor agonists if lipase is elevated without active symptoms of pancreatitis, until further evaluation can be done 2.

From the Research

GLP-1 Receptor Agonists and Pancreatitis Risk

• The relationship between GLP-1 receptor agonists and the risk of pancreatitis is complex and has been studied extensively 3, 4, 5, 6, 7.
• A study published in the Journal of Clinical Medicine found that the use of GLP-1 receptor agonists did not increase the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus 3.
• However, a case report published in Clujul Medical reported a case of acute pancreatitis in a patient treated with GLP-1 receptor agonist, suggesting that acute pancreatitis can be considered a side effect of GLP-1 treatment 4.

Elevated Lipase Levels and GLP-1 Receptor Agonists

• A study published in Endocrine Practice found that GLP-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors were associated with increased levels of serum lipase and amylase in patients with type 2 diabetes 5.
• The study suggested that the increased levels of serum lipase and amylase may indicate the presence of pancreatic inflammation, but it is unclear whether this finding may lead to acute pancreatitis or chronic pancreatitis 5.

Stopping GLP-1 Receptor Agonists due to Elevated Lipase Levels

• There is no clear consensus on whether to stop GLP-1 receptor agonists if lipase is elevated without active symptoms of pancreatitis 3, 4, 5, 6, 7.
• A systematic review and meta-analysis published in Diabetes, Obesity and Metabolism found no evidence that treatment with GLP-1 receptor agonists increases the risk of acute pancreatitis in patients with type 2 diabetes 6.
• An updated meta-analysis published in Minerva Endocrinology found no association between GLP-1 receptor agonists and the risk of pancreatitis or pancreatic cancer 7.

Clinical Considerations

• Clinicians should carefully monitor patients taking GLP-1 receptor agonists for signs and symptoms of pancreatitis, even if lipase levels are elevated without active symptoms of pancreatitis 3, 4, 5, 6, 7.
• The decision to stop GLP-1 receptor agonists due to elevated lipase levels should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 3, 4, 5, 6, 7.