What are the precautions for using Dapagliflozin (Forxiga) in patients with a history of pancreatitis or at risk for pancreatitis?

Dapagliflozin and Pancreatitis: Precautions and Management

Dapagliflozin (Forxiga) has no specific contraindications related to pancreatitis history, but caution is warranted as rare case reports suggest a possible association between SGLT2 inhibitors and acute pancreatitis. While pancreatitis is not listed as a known adverse effect in the FDA label for dapagliflozin, several case reports document this potential association.

Risk Assessment and Monitoring

• Dapagliflozin's FDA label does not list pancreatitis as a known adverse effect or contraindication, unlike GLP-1 receptor agonists which carry specific warnings about pancreatitis 1
• Case reports document acute pancreatitis developing shortly after initiation of dapagliflozin therapy, with symptoms resolving upon discontinuation 2, 3
• Similar cases have been reported with other SGLT2 inhibitors such as empagliflozin, suggesting this may be a class effect 4, 5
• The mechanism linking SGLT2 inhibitors to pancreatitis is not well established, but appears to be idiosyncratic rather than dose-dependent 2

Recommendations for Patients with History of Pancreatitis

• Baseline Assessment: Before initiating dapagliflozin in patients with history of pancreatitis, evaluate for other risk factors for pancreatitis (gallstones, hypertriglyceridemia, alcohol use) 2
• Patient Education: Inform patients about symptoms of acute pancreatitis (severe abdominal pain radiating to the back, nausea, vomiting) and advise to seek immediate medical attention if these develop 3
• Monitoring: Consider monitoring lipase levels periodically in patients with history of pancreatitis who are started on dapagliflozin 4
• Alternative Medications: In patients with multiple episodes of pancreatitis or recent pancreatitis, consider alternative antidiabetic medications that have no reported association with pancreatitis 6

Management of Suspected Dapagliflozin-Induced Pancreatitis

• Immediately discontinue dapagliflozin if pancreatitis is suspected 3
• Do not rechallenge with dapagliflozin if pancreatitis is confirmed, as recurrence has been documented upon rechallenge 3
• Manage acute pancreatitis according to standard protocols 6
• Consider switching to alternative antidiabetic medications with no known association with pancreatitis 6

Special Considerations

• Patients with type 2 diabetes on dapagliflozin may develop euglycemic ketoacidosis with concurrent pancreatitis, which can complicate diagnosis as glucose levels may be normal or only mildly elevated 7
• Dapagliflozin is not recommended for patients with severe renal impairment (eGFR <45 mL/min/1.73 m²) for glycemic control, which may be relevant for patients with chronic pancreatitis and associated complications 1
• Patients with hypertriglyceridemia and history of pancreatitis may be at higher risk and require closer monitoring if dapagliflozin therapy is initiated 7

Clinical Decision Algorithm

1. For patients with no history of pancreatitis: Standard precautions apply when initiating dapagliflozin 1
2. For patients with single episode of pancreatitis in distant past (>1 year) with identified and corrected cause (e.g., gallstones removed): Consider dapagliflozin with careful monitoring 2
3. For patients with recent pancreatitis (<1 year) or recurrent pancreatitis: Consider alternative antidiabetic agents 3
4. For patients with ongoing risk factors for pancreatitis (e.g., hypertriglyceridemia): Address underlying risk factors before considering dapagliflozin or choose alternative agents 7

While the absolute risk appears low based on available evidence, clinicians should maintain vigilance for this potential adverse effect, especially in the first few weeks after initiating therapy with dapagliflozin.