Post‐semaglutide weight regain in females with obesity: Associations with gut microbiota, bile acid metabolism, and central nervous system
Authors' conclusion
The recurrence of WR and increased appetite after semaglutide withdrawal coincided with reversals in gut microbiota and related metabolic profiles. This pattern of changes may implicate gut-derived signals in the reactivation of central appetite pathways, providing a basis for investigating strategies to sustain weight loss.
Study context
- Population
- Women with obesity; parallel HFD-fed female rats (4-week semaglutide, 4-week withdrawal)finished treatment
- Participants
- 28 women
- Exposure
- 36-week semaglutide treatment followed by 12-week withdrawal
- Semaglutiden = 28
- Outcome
- Weight change and WR after withdrawal
Main finding
As reported in the abstract
Weight loss during treatment
−16.9 ± 4.8 kg
Weight regain (WR) post-withdrawal
71.4%
WR magnitude post-withdrawal
+5.1 ± 1.6 kg
Appetite rebound (≥30% increase in VAS score and sustained ≥300 kcal/day rise)
78.5%
Observational data: associations, not effects.
Further findings
Animal studies: post-withdrawal mechanisms
- Gut microbiota dysbiosis (increased Firmicutes/Bacteroidota ratio, reduced Clostridium sensu stricto 1)
- Decreased ursodeoxycholic acid levels and downregulated hypothalamic TGR5 expression
- Hypothalamic orexigenic signaling (AgRP/NPY) rebounded; anorexigenic pathways (POMC/MC4R) attenuated
- Hepatic and adipose lipid metabolism improvements partially persisted (maintained AMPK/SIRT1 activation, AKT/mTOR suppression)
- HFD-fed female rats
Original publication
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