Glycaemic changes during early semaglutide treatment: a case of pancreatic adenocarcinoma

Glucagon-like peptide-1 receptor agonists are widely used for the management of obesity and dysglycaemia, and current evidence does not support a causal association with pancreatic cancer. We report a 55-year old woman with obesity and prediabetes who started once-weekly semaglutide 0.25 mg for weight management and glycaemic control. Baseline fasting plasma glucose was 107 mg/dL and glycated haemoglobin was 6.0%. After one month, despite a 4 kg weight loss and no significant gastrointestinal symptoms, fasting plasma glucose increased to 169 mg/dL and glycated haemoglobin to 6.6%. Latent autoimmune diabetes in adults was excluded by negative autoantibodies and preserved C-peptide. Further evaluation revealed markedly elevated carbohydrate antigen 19-9 and pancreatic magnetic resonance imaging demonstrated a 4 × 3 cm irregular mass in the pancreatic head. Surgical exploration identified liver metastases, and biopsy confirmed metastatic pancreatobiliary adenocarcinoma. This case highlights that atypical glycaemic changes during early semaglutide treatment should be interpreted cautiously, particularly during subtherapeutic dose escalation. Such observations do not imply causality, but may warrant individualized assessment when accompanied by additional clinical suspicion.