Trelagliptin-induced polyarthritis with positive dechallenge: First reported case

Trelagliptin is a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor approved for type 2 diabetes mellitus (T2DM), offering convenient once-weekly dosing with sustained glycemic control. Musculoskeletal adverse effects have been recognized across the DPP-4 inhibitor class, and the United States Food and Drug Administration issued a class-wide safety warning for severe arthralgia in 2015. However, trelagliptin-associated polyarthritis has not been previously documented in the published literature, and the World Health Organization VigiBase pharmacovigilance database records only six musculoskeletal adverse events for trelagliptin to date, none of which constitute polyarthritis. We report the first known case of trelagliptin-induced polyarthritis in a 54-year-old male with newly diagnosed T2DM of limited financial means, who developed acute seronegative symmetric polyarthritis affecting bilateral wrists, knees, and ankles within eight days of commencing trelagliptin 100 mg once weekly. Autoimmune serology was entirely negative, inflammatory markers were elevated, and joint radiographs demonstrated no erosions. Symptoms resolved fully within five days of drug withdrawal without recurrence at 3-month follow-up. Causality assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 7, classifying the reaction as probable. This case extends the pharmacovigilance signal for DPP-4 inhibitor-induced inflammatory arthritis to trelagliptin and underscores the need for clinical vigilance with this increasingly prescribed once-weekly agent.