Can Farxiga Cause Pancreatitis?
Farxiga (dapagliflozin) can cause acute pancreatitis, though it is rare, and the drug should be discontinued immediately if pancreatitis is suspected.
Evidence from Guidelines
The most recent diabetes guidelines acknowledge that while SGLT2 inhibitors like dapagliflozin have an "unknown" risk level for pancreatitis, the class does not carry the same established association seen with GLP-1 receptor agonists or DPP-4 inhibitors 1. However, this "unknown" designation does not mean the risk is absent—it reflects limited large-scale data rather than proven safety 1.
For comparison, GLP-1 receptor agonists carry a "potential" risk designation, with guidelines explicitly stating: "acute pancreatitis has been reported, but causality has not been established. Do not initiate if at high risk for pancreatitis, and discontinue if pancreatitis is suspected" 1. The American Heart Association similarly notes that acute pancreatitis has been reported with DPP-4 inhibitors, though causality remains unestablished, and recommends discontinuation if suspected 1.
Case Report Evidence
Multiple published case reports document dapagliflozin-induced acute pancreatitis with temporal relationships and positive rechallenge:
A 58-year-old male developed acute pancreatitis with no other risk factors shortly after starting dapagliflozin; symptoms resolved upon discontinuation with no recurrence 2
A 51-year-old male developed pancreatitis five days after starting dapagliflozin, improved after stopping the drug, then developed recurrent pancreatitis when rechallenged a year later—this positive rechallenge strongly supports causality 3
Other SGLT2 inhibitors in the same class have similar case reports: canagliflozin 4 and empagliflozin 5, 6 have each been implicated in acute pancreatitis cases where other etiologies were excluded.
Clinical Approach When Pancreatitis is Suspected
Discontinue dapagliflozin immediately if a patient presents with severe abdominal pain, nausea, or vomiting 2, 3. The diagnostic workup should include:
- Serum lipase or amylase levels (lipase >3× upper limit of normal supports diagnosis) 7
- Liver function tests (early elevation of aminotransferases or bilirubin suggests biliary etiology) 7
- Right upper quadrant ultrasound to exclude gallstones 7, 8
- Fasting lipid panel and serum calcium to identify hypertriglyceridemia (>11.3 mmol/L) or hypercalcemia 7
- Detailed alcohol history (≥80 g/day for >5 years) 7
- Comprehensive medication review, as drug-induced pancreatitis is commonly overlooked 4, 6
Key Clinical Pitfalls
Do not rechallenge with dapagliflozin after an episode of suspected drug-induced pancreatitis—one case report documents recurrent pancreatitis upon rechallenge, confirming the causal relationship 3. The goal is to identify a definitive etiology in 75-80% of acute pancreatitis cases; drug-induced causes should not be dismissed simply because they are rare 7.
Do not assume SGLT2 inhibitors are safe from pancreatitis risk simply because guidelines list the risk as "unknown"—this reflects insufficient data rather than proven safety, and the temporal relationship in published cases is compelling 1, 2, 3.
Patients starting SGLT2 inhibitors should be counseled about symptoms of acute pancreatitis (severe epigastric pain radiating to the back, nausea, vomiting) and instructed to seek immediate care and stop the medication if these occur 3.