Should patients with a history of pancreatitis avoid using Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

SGLT2 Inhibitors in Patients with History of Pancreatitis

SGLT2 inhibitors should be avoided in patients with a history of pancreatitis due to emerging evidence of association with pancreatitis recurrence and new-onset cases. 1

Risk Assessment

SGLT2 inhibitors have been associated with pancreatitis in multiple case reports and pharmacovigilance analyses:

• Disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data has identified a significant signal between SGLT2 inhibitors and pancreatitis 1
• The risk appears highest with empagliflozin (PRR = 3.9), followed by canagliflozin (PRR = 3.6) and dapagliflozin (PRR = 3.2) 1
• Case reports have documented pancreatitis occurring shortly after initiation of SGLT2 inhibitors, with recurrence upon rechallenge 2, 3

Clinical Decision Algorithm

1. For patients with history of pancreatitis:

   • Avoid SGLT2 inhibitors as first-line therapy
   • Consider GLP-1 receptor agonists instead, which surprisingly show lower risk of pancreatitis recurrence compared to SGLT2 inhibitors in patients with prior pancreatitis history 4

2. For patients currently on SGLT2 inhibitors who develop abdominal pain:

   • Immediately evaluate for pancreatitis (lipase, amylase, imaging)
   • Discontinue the SGLT2 inhibitor if pancreatitis is suspected 3
   • Do not rechallenge with the same or different SGLT2 inhibitor after recovery

3. For patients requiring diabetes medication with history of pancreatitis:

   • Consider metformin (if not contraindicated)
   • Consider insulin therapy
   • Evaluate other medication options based on cardiovascular and renal risk profiles

Evidence Analysis

The FDA label for dapagliflozin specifically mentions pancreatitis as a risk factor for ketoacidosis when using SGLT2 inhibitors: "Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis" 5. This suggests awareness of the potential relationship between SGLT2 inhibitors and pancreatic complications.

The American College of Cardiology guidelines list "history of pancreatitis" as a consideration that may prompt use of alternative agents to SGLT2 inhibitors 6. While this is primarily mentioned in the context of GLP-1 receptor agonists, it highlights the importance of considering pancreatic history in medication selection.

Monitoring and Management

For patients who must use SGLT2 inhibitors despite history of pancreatitis (due to compelling cardiovascular or renal indications):

• Educate patients about symptoms of pancreatitis (severe abdominal pain radiating to the back, nausea, vomiting)
• Monitor for early signs of pancreatitis
• Consider more frequent follow-up in the initial weeks after starting therapy
• Have a low threshold for discontinuation if symptoms develop

Conclusion

The evidence suggests a potential association between SGLT2 inhibitors and pancreatitis. While the absolute risk may be low, the serious nature of pancreatitis and the availability of alternative diabetes medications make it prudent to avoid SGLT2 inhibitors in patients with a history of pancreatitis. This approach prioritizes patient safety and reduces morbidity risk.