Hormone PYY does not Explain the Variability in Weight Loss After Roux-en-Y Gastric Bypass: Evidence From a Meta-Analysis.

BACKGROUND: Peptide YY (PYY) plays a key role in postprandial satiety and is markedly increased after Roux-en-Y gastric bypass (RYGB). While GLP-1 has been widely studied, the role of PYY as a predictor of weight loss success remains unclear. Some patients are considered non-responders, achieving < 50% excess BMI loss (EBMIL) or experiencing significant weight regain. This systematic review and meta-analysis aimed to compare fasting PYY levels and postprandial area under the curve (AUC) between RYGB responders and non-responders. METHODS: Following PRISMA guidelines, PubMed, Embase, and Cochrane databases were searched for observational or interventional studies assessing PYY in adult RYGB patients stratified by weight loss response. Primary outcomes were fasting PYY levels and PYY AUC after standardized meals. Random-effects meta-analysis was conducted using Review Manager 5.4. Mean differences (MD) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed via Cochran’s Q and I². RESULTS: Five studies were included in the systematic review (92 non-responders and 89 responders), contributing to the fasting PYY meta-analysis, which showed no significant difference between groups (MD 1.71 pg/mL; 95% CI − 5.22 to 8.63; I² = 0%). Four studies reported AUC, also showing no difference (MD 53.16 pg·min/mL; 95% CI − 1726.29 to 1832.61; I² = 0%). Several studies observed lower satiety scores and attenuated appetite suppression in non-responders despite similar PYY profiles. No significant genetic variants in PYY or its receptor were associated with weight loss outcomes. CONCLUSION: RYGB responders and non-responders have comparable fasting and postprandial PYY concentrations. These findings suggest that differential weight loss after RYGB is likely mediated by factors beyond PYY secretion, including neural, behavioral, or other hormonal mechanisms.