Pantoprazole exposure linked to insulin autoimmune syndrome in case report

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Frontiers in Medicine Published June 3, 2026 Medically reviewed June 3, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider PPI exposure as a possible trigger for insulin autoimmune syndrome in patients with unexplained hypoglycemia.

This is a case report with a literature review describing a patient who developed insulin autoimmune syndrome (IAS) in temporal association with exposure to the proton pump inhibitor (PPI) pantoprazole. The patient also received beraprost sodium, clopidogrel, and atorvastatin calcium, but the report focuses on pantoprazole as the possible trigger. Genetic testing revealed HLA-DRB1*0403, DQB1*0302, and DQA1*0301 alleles, which may confer susceptibility.

After discontinuation of pantoprazole, the patient's hypoglycemic episodes resolved and insulin autoantibody (IAA) levels gradually decreased to the normal range. Insulin levels also improved. No adverse events or serious adverse events were reported; the only intervention was PPI discontinuation.

The authors note that this is a single case report, so causality and generalizability are limited. The report aims to alert clinicians to the possibility of PPI-associated IAS, which may help avoid misdiagnosis and enable timely treatment. No funding or conflicts of interest were reported.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

BackgroundInsulin autoimmune syndrome (IAS) is an autoimmune endocrine disorder characterized by hyperinsulinemia, positive insulin autoantibodies (IAA), and hypoglycemia. IAS was previously thought to be induced by drugs containing thiol groups.ObjectiveWe describe a case highlighting that IAS may be temporally associated with a proton pump inhibitor (PPI) exposure. This article reports a patient who took beraprost sodium, clopidogrel, atorvastatin calcium, and the PPI pantoprazole and was subsequently diagnosed with IAS, presenting with a high IAA level, refractory hypoglycemia, and markedly elevated insulin levels. The patient’s hypoglycemic episodes were ultimately relieved after discontinuation of the PPI, accompanied by a gradual decrease in the IAA level to the normal range.Key findingsHLA analysis revealed HLA-DRB1*0403, DQB1*0302, and DQA1*0301, indicating the patient’s genetic susceptibility to IAS, which was possibly triggered by the PPI.Clinical relevanceThis case report may alert clinicians to possible PPI-associated IAS, helping to avoid misdiagnosis and enable patients to receive timely treatment.