Is Dapagiflon (SGLT2 inhibitor) safe to use in patients with pancreatitis?

Safety of Dapagliflozin in Patients with Pancreatitis

Dapagliflozin should be used with caution in patients with a history of pancreatitis due to reported cases of SGLT2 inhibitor-associated acute pancreatitis, and is not recommended in patients with active pancreatitis.

Risk of Pancreatitis with SGLT2 Inhibitors

• While not listed as a common adverse effect in major guidelines, there have been multiple case reports and analyses linking SGLT2 inhibitors, including dapagliflozin, to acute pancreatitis 1, 2, 3
• A comprehensive analysis of the FDA adverse event reporting system found 757 reports of acute pancreatitis associated with SGLT2 inhibitors, with approximately 83% occurring within 6 months of initiation 4
• The FDA drug label for dapagliflozin specifically mentions that "type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors for ketoacidosis" 5
• Case reports document recurrence of pancreatitis upon rechallenge with dapagliflozin, suggesting a causal relationship 1

Safety Considerations for Dapagliflozin Use

• The FDA label identifies several safety concerns with dapagliflozin, including diabetic ketoacidosis, volume depletion, and urinary tract infections, but does not specifically list pancreatitis as a labeled adverse effect 5
• Patients with pancreatic disorders are identified as being at higher risk for ketoacidosis, which is a serious adverse effect of SGLT2 inhibitors 5
• The European Society of Cardiology guidelines recommend dapagliflozin for cardiovascular risk reduction but do not specifically address its use in patients with pancreatitis 6

Risk Factors and Monitoring

• Combination therapy with other antidiabetic medications may increase risk - concomitant use of SGLT2 inhibitors with DPP-4 inhibitors showed an adjusted odds ratio of 1.39 for acute pancreatitis 4
• The median time to development of acute pancreatitis was 54 days (IQR 14-131) after starting an SGLT2 inhibitor 4
• Patients should be monitored for signs and symptoms of pancreatitis, including abdominal pain radiating to the back, nausea, and vomiting 1, 2

Recommendations for Clinical Practice

• For patients with active pancreatitis, avoid initiating dapagliflozin until resolution 1, 2
• For patients with a history of pancreatitis who require dapagliflozin for cardiovascular or renal benefits:
  • Consider alternative glucose-lowering agents if glycemic control is the primary goal 6
  • If using dapagliflozin, educate patients about symptoms of pancreatitis and instruct them to seek immediate medical attention if such symptoms occur 1
  • Monitor closely during the first 6 months of therapy, when risk appears highest 4
• For patients who develop pancreatitis while on dapagliflozin:
  • Discontinue the medication immediately 1, 2
  • Avoid rechallenge, as recurrence has been documented 1

Alternative Considerations

• For patients with type 2 diabetes and a history of pancreatitis who need cardiovascular protection, GLP-1 receptor agonists like liraglutide may be considered as an alternative, though they also carry pancreatitis risk 6
• For patients with heart failure who need an SGLT2 inhibitor despite pancreatitis history, close monitoring is essential, especially during the initial months of therapy 6, 4