Acute Interstitial Nephritis Associated with Oral Semaglutide

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes, obesity, and cardiorenal protection. Acute interstitial nephritis (AIN) has been reported with subcutaneous GLP-1RAs but has not previously been described with the oral formulation. We report a 56-year-old Asian man with type 2 diabetes who developed biopsy-proven AIN after 9.5 weeks of oral semaglutide during a clinical trial "ASCEND PLUS Trial ( A Study of Cardiovascular Events iN Diabetes Plus ) that investigated the effect of oral semaglutide on cardiovascular events in patients with type 2 diabetes". Baseline renal function was normal (serum creatinine 74 μmol/L, eGFR >90 mL/min/1.73 m 2 ). Four weeks after commencing oral semaglutide, the patient presented with frothy urine and proteinuria, acute kidney injury (creatinine 258 μmol/L), metabolic acidosis, anaemia, and peripheral eosinophilia. Kidney biopsy demonstrated active non-granulomatous tubulointerstitial nephritis with eosinophils consistent with a drug-related aetiology, alongside mild diabetic glomerulopathy and chronic parenchymal scarring. Creatinine rose to 350 μmol/L despite drug discontinuation. Treatment with oral prednisolone (60 mg/day, tapered over twelve weeks) produced progressive improvement: creatinine fell to 164 μmol/L with reduction in proteinuria over 16 weeks after drug discontinuation. Naranjo adverse drug reaction probability assessment scored 5 (‘probable'). No alternative culprit drug was identified; all concomitant medications had been stable long-term. This is, to our knowledge, the first report of biopsy- confirmed AIN associated with oral semaglutide. The case extends the pharmacovigilance signal for GLP-1RA-associated AIN to the oral formulation, demonstrates steroid responsiveness, and highlights that renal function monitoring during initiation and dose escalation of all incretin-based therapies should be considered.