Possible Attenuation of Early Weight Loss During Tirzepatide Therapy in a Patient Treated With Levosulpiride: A Case Report and Mechanistic Hypothesis

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, induces significant weight loss and glycemic improvement. Dopaminergic pathways are critically involved in appetite regulation and reward processing, and the pharmacological modulation of dopamine signaling may influence metabolic responses to incretin-based therapies. We report the case of a 54-year-old woman with obesity and newly diagnosed type 2 diabetes mellitus (T2DM) who initiated tirzepatide therapy while receiving levosulpiride for functional dyspepsia. During the co-administration of tirzepatide 5 mg weekly and levosulpiride, only modest weight reduction was observed, followed by a plateau. After the discontinuation of levosulpiride and the titration of tirzepatide to 7.5 and 10 mg weekly, a marked and progressive reduction in body weight occurred, with an overall loss of 11 kg from baseline. Glycemic control improved substantially (glycated hemoglobin {HbA1c}: 5.0%), and no episode of pancreatitis occurred despite asymptomatic lipase elevation. This case raises the hypothesis of a potential pharmacodynamic interaction between dopaminergic antagonism and incretin receptor agonism, possibly mediated by opposing effects on gastric motility and central reward pathways. Although causality cannot be established, clinicians should consider concomitant neuroactive medications in cases of suboptimal early weight response to dual incretin therapy.