SGLT2 Inhibitor–associated Bullous Pemphigoid: A Comprehensive Review of Clinical Phenotypes, Latency, Immunopathologic Findings, Proposed Mechanisms, and Clinical Outcomes
Saud Abdullah Alsharif *
Dermatology Attachment, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
Fahad Alrowais
Consultant Dermatology, Prince Sultan Military Hospital, Riyadh, Saudi Arabia.
*Author to whom correspondence should be addressed.
Abstract
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder frequently diagnosed in older adults. The expanding use of sodium–glucose cotransporter 2 (SGLT2) inhibitors makes the assessment of suspected medication-associated BP clinically relevant. This narrative review examines published clinical reports, observational comparisons, pharmacovigilance findings and immunopathological literature available through August 2026. Reports describe BP during treatment with ipragliflozin, empagliflozin and dapagliflozin, with extractable onset intervals of approximately five, one and four months, respectively. A separate report described an initial pemphigus phenotype after tofogliflozin exposure and subsequent BP during prolonged linagliptin treatment, complicating drug attribution. Subepidermal blistering and linear basement-membrane IgG/C3 deposition supported diagnosis in reported cases. Negative circulating BP180/BP230 results in one case did not exclude BP supported by tissue findings. However, confirmation of BP does not establish its precipitating medication. A Finnish population study found no increased BP risk with SGLT2 inhibitors, while a Taiwanese matched cohort reported a lower adjusted hazard among users than non-users. Comparative evidence also emphasises the competing association between dipeptidyl peptidase-4 inhibitors and BP. No reproducible SGLT2-specific immunopathological phenotype or causal mechanism has been demonstrated. Clinical management requires prompt diagnostic assessment, complete medication chronology, severity-based treatment and co-ordinated appraisal of the benefits and risks of changing antidiabetic or cardiorenal therapy. Current evidence supports individual clinical vigilance but not a proven class-wide excess BP risk.
Keywords: Bullous pemphigoid, SGLT2 inhibitor, empagliflozin, dapagliflozin, ipragliflozin, drug causality, direct immunofluorescence, pharmacovigilance