The Effects of Glucagon-Like Peptide-1 Receptor Agonists on Chemosensory Function and Ingestive Behavior

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce energy intake and produce clinically meaningful weight loss, but the chemosensory and behavioral contributions to these effects remain poorly characterized. This study examined whether GLP-1RA use was associated with differences in chemosensory function and ingestive behavior in adults with obesity. In this cross-sectional study, 79 adults with obesity were categorized as "pre-use": individuals eligible for GLP-1RA treatment but not yet using one (n = 27), 1-month GLP-1RA users (n = 25), or 6-month GLP-1RA users (n = 27). Participants completed laboratory-based assessments of taste detection thresholds, suprathreshold taste intensity, taste hedonics, fat taste, chemesthesis, olfactory function, and cephalic-phase salivary response. Questionnaires assessed food noise, cue responsivity, cravings, and food reward. Dietary intake was assessed using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24). Sweet taste detection thresholds differed by group (p=0.001), with higher thresholds in both GLP-1RA groups compared with pre-use controls (1 month: p=0.0078; 6 months: p=0.0024). Other qualities showed consistent directional, but non-significant shifts. Suprathreshold taste intensity, taste hedonics, olfactory function, and chemesthesis were largely unchanged, except for a limited fat-intensity difference at medium linoleic acid concentration. Food Noise Questionnaire scores were lower in 6-month users than in pre-use controls (P = .026). 6-month users also showed lower cue responsivity, craving, food reward, and energy intake. Protein intake did not significantly differ across groups. Overall, GLP-1RA use was associated with lower food salience, cravings, cue responsiveness, food reward, and energy intake, while chemosensory differences were limited mainly to sweet taste detection. Clinical Trial Registry: ClinicalTrials.gov: NCT07611201; https://clinicaltrials.gov/study/NCT07611201.