Risk of Pancreatitis with Dapagliflozin and Teneligliptin
Both dapagliflozin (an SGLT2 inhibitor) and teneligliptin (a DPP-4 inhibitor) carry a documented but rare risk of acute pancreatitis, though the evidence is stronger for DPP-4 inhibitors than for SGLT2 inhibitors. 1, 2, 3
DPP-4 Inhibitors (Teneligliptin) and Pancreatitis Risk
Rare but increased rates of pancreatitis have been reported with DPP-4 inhibitors as a class. 1
Evidence Quality and Context
Clinical trials with well-selected diabetic patients showed no increased risk of acute pancreatitis with any of the five commercialized DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin) in rather short-term studies. 2
Real-life cohort studies initially showed no increased incidence of pancreatitis with DPP-4 inhibitors compared with other glucose-lowering agents, though this finding was later challenged by a case-control study. 2
Several anecdotal clinical cases of pancreatitis have been reported with sitagliptin and vildagliptin, and an increased relative risk was reported to the FDA with sitagliptin versus other comparators, though reporting bias cannot be excluded. 2
Important Clinical Context
Diabetic patients have an inherently increased risk of pancreatitis compared to nondiabetic patients, independent of medication use. 2
The absolute risk remains low, but postmarketing surveillance and ongoing large prospective trials continue to monitor this safety signal. 2
SGLT2 Inhibitors (Dapagliflozin) and Pancreatitis Risk
Pancreatitis is an exceedingly rare adverse effect of SGLT2 inhibitors, including dapagliflozin, with only scattered case reports in the literature. 3, 4
Evidence Quality
There are only a few published cases of acute pancreatitis linked to SGLT2 inhibitor administration. 3
Case reports describe acute pancreatitis occurring shortly after initiation of dapagliflozin in patients with no other identifiable risk factors, with resolution after drug discontinuation. 3
Canagliflozin (another SGLT2 inhibitor in the same class as dapagliflozin) has been reported to cause pancreatitis in rare cases. 4
Importantly, pancreatitis is NOT listed as a warning or precaution in the FDA-approved dapagliflozin drug label, which focuses on diabetic ketoacidosis, volume depletion, urinary tract infections, hypoglycemia with concomitant insulin/secretagogues, and Fournier's gangrene as the primary safety concerns. 5
Combination Therapy Safety
Clinical trials evaluating the combination of SGLT2 inhibitors and DPP-4 inhibitors show that co-administration does not carry additional safety concerns beyond each individual drug. 6
The combination of these drug classes is considered safe and effective, with complementary mechanisms of action. 6
Cardiovascular trials have demonstrated cardiovascular safety of DPP-4 inhibitors and reduction in cardiovascular events with SGLT2 inhibitors. 6
Clinical Decision Algorithm
When Prescribing This Combination:
1. Assess baseline pancreatitis risk factors:
- History of pancreatitis or pancreatic surgery (type 2 diabetes and pancreatic disorders are risk factors for ketoacidosis with SGLT2 inhibitors, which may be confused with pancreatitis). 5
- Hypertriglyceridemia, alcohol abuse, gallstone disease. 4
- Multiple medications that could cause drug-induced pancreatitis. 4
2. Patient education is critical:
- Educate patients on signs and symptoms of pancreatitis: severe abdominal pain (often radiating to the back), nausea, vomiting. 3
- Instruct patients to seek immediate medical attention if these symptoms occur. 3
- Distinguish pancreatitis symptoms from ketoacidosis symptoms (nausea, vomiting, abdominal pain, but also with labored breathing and malaise). 5
3. If pancreatitis occurs:
- Discontinue both medications immediately. 3
- Complete thorough workup to exclude other etiologies (gallstones, alcohol, hypertriglyceridemia, hypercalcemia). 3, 4
- Do not rechallenge with either medication if drug-induced pancreatitis is confirmed. 3
Critical Caveats
Drug-induced pancreatitis is commonly overlooked in patients with multiple comorbidities taking numerous medications. 4
The timing of symptom onset after drug initiation is a key diagnostic clue—most cases occur within weeks to months of starting therapy. 3, 4
For dapagliflozin specifically, the more pressing safety concerns are diabetic ketoacidosis (which can be fatal and may present with abdominal pain mimicking pancreatitis), volume depletion, and urinary tract infections. 5
Prompt identification of drug-induced pancreatitis can decrease morbidity and mortality, particularly given the rare but serious nature of this adverse effect. 4