Nutritional intake changes during GLP-1 receptor agonist therapy: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists, including the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide, produce substantial weight loss, yet their effect on objectively measured dietary intake has not been quantitatively synthesized. We assessed their impact on ad libitum lunch energy intake. METHODS: We searched six databases through March 31, 2026, for studies reporting quantitative dietary outcomes in adults receiving a GLP-1 or dual GIP/GLP-1 receptor agonist. Randomized or crossover placebo-controlled trials lasting at least four weeks that reported standardized ad libitum lunch intake were pooled using a DerSimonian-Laird random-effects model. Prespecified sensitivity analyses included restricted maximum likelihood (REML) and Paule-Mandel estimators, a 95% prediction interval, a subgroup analysis, a leave-one-out analysis, and an exploratory three-week phase 1 tirzepatide trial. RESULTS: Sixteen studies were included in the systematic review; four arms from three trials (209 participants) contributed to the primary meta-analysis. The pooled treatment difference in ad libitum lunch energy intake was -1132 kJ (95% confidence interval [CI] -1449 to -815), approximately -271 kcal, with no heterogeneity (I-squared = 0%; 95% prediction interval -1828 to -436 kJ). Adding the phase 1 trial (k = 5) increased the effect to -1421 kJ but introduced substantial heterogeneity (I-squared = 70%). The semaglutide-versus-tirzepatide difference was not significant (p = 0.154). CONCLUSIONS: GLP-1 receptor agonist therapy markedly reduces acute energy intake under standardized meal tests, but real-world habitual intake remains underreported. Structured nutritional counseling emphasizing adequate protein should complement pharmacotherapy.