Nausea (Drug-Related)
A common side effect reported by 15-44% of patients initiating GLP-1 receptor agonist therapy. Drug-related nausea typically peaks during initial weeks and dose titration, then diminishes. Gradual dose escalation, smaller meals, and dietary adjustments help manage this side effect.
Technical Context
GLP-1 RA nausea mechanisms: central (GLP-1R activation in the area postrema and nucleus tractus solitarius — brainstem emetic centres), peripheral (delayed gastric emptying causing gastric distension and vagal afferent stimulation), and conditioned (anticipatory nausea in patients who experienced initial episodes). Incidence varies by compound and dose: semaglutide 2.4mg ~44% (STEP trials), tirzepatide 15mg ~31% (SURMOUNT), liraglutide 3.0mg ~39% (SCALE). Temporal pattern: peaks during first 4-8 weeks and dose escalation periods, then diminishes (tachyphylaxis of the emetic response). Management strategies: gradual dose titration (the primary approach), smaller meal portions, avoiding high-fat foods, eating slowly, staying hydrated, and anti-emetic medications (ondansetron, prochlorperazine) for persistent symptoms. Nausea is the most common reason for GLP-1 RA discontinuation in clinical practice.