Semaglutide initiation linked to atypical glycemic worsening in patient with occult pancreatic adenocarcinoma

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are widely utilized for managing obesity and dysglycemia, demonstrating significant benefits in weight loss and glycemic control. While generally well-tolerated, concerns about a potential link to pancreatic cancer have been raised, though current extensive evidence from randomized controlled trials and meta-analyses does not support a causal association. This case highlights a critical gap: how to interpret atypical clinical responses, particularly unexpected glycemic deterioration, in patients initiating GLP-1 RA therapy, especially when underlying pathologies might be present but undiagnosed.

This case report details a 55-year-old woman with obesity and prediabetes who initiated once-weekly semaglutide 0.25 mg for weight management and glycemic control. Baseline measurements included fasting plasma glucose (FPG) of 107 mg/dL and glycated hemoglobin (HbA1c) of 6.0%. After one month of treatment, despite experiencing 4 kg weight loss and no significant gastrointestinal symptoms, her FPG and HbA1c were re-evaluated. Further diagnostic workup included autoantibody testing and C-peptide measurement to exclude latent autoimmune diabetes in adults, followed by carbohydrate antigen 19-9 (CA 19-9) measurement and pancreatic magnetic resonance imaging (MRI) due to the atypical glycemic response.

After one month of once-weekly semaglutide 0.25 mg, the patient's glycemic control unexpectedly worsened despite a 4 kg weight loss. Her fasting plasma glucose increased from 107 mg/dL at baseline to 169 mg/dL, and glycated hemoglobin (HbA1c) rose from 6.0% to 6.6%. Latent autoimmune diabetes in adults was ruled out by negative autoantibodies and preserved C-peptide levels. Subsequent evaluation revealed a markedly elevated CA 19-9 level. Pancreatic MRI demonstrated a 4 × 3 cm irregular mass located in the pancreatic head. Surgical exploration confirmed the presence of liver metastases, and a biopsy of the pancreatic lesion ultimately confirmed a diagnosis of metastatic pancreatobiliary adenocarcinoma. This observation underscores that while semaglutide is effective for many, individual responses can vary significantly. > The patient's fasting plasma glucose increased by 57.9% (from 107 mg/dL to 169 mg/dL) and HbA1c by 10% (from 6.0% to 6.6%) within one month of semaglutide initiation.