Presentation (CTI)

OBJECTIVES: GLP-1 receptor agonists (GLP-1 RAs) are effective in achieving clinically meaningful weight loss in patients with obesity, yet treatment discontinuation is common in real-world settings. Weight regain following cessation may drive treatment reinitiation and increased healthcare resource use (HCRU). This review aimed to characterise post-discontinuation weight trajectories and treatment reinitiation patterns, and to evaluate whether nutritional support variables are captured in real-world datasets - a prerequisite for cost-effectiveness modelling of adjunct lifestyle interventions.
METHODS: A targeted literature review was conducted in PubMed (January 2021-April 2026), limited to English-language human studies on GLP-1 RA therapy, weight outcomes, and nutritional variables, across populations in Europe and North America.
RESULTS: Fourteen studies were included (8 RCTs, 6 observational) and six studies reported post-discontinuation weight data. In STEP 1 trial extension, 67% of lost weight was regained within 12 months of stopping semaglutide, and in SURMOUNT-4 14% of body weight was regained within 52 weeks of stopping tirzepatide. In a real-world cohort of 7,881 patients, early discontinuation substantially attenuated weight loss (−3.6% vs −11.9% in persistent users). Critically for HRU, each 1% of post-discontinuation weight gain was associated with an increased hazard of treatment reinitiation up to 2.8% (n=41,792), creating a potentially costly cycle of cessation and re-prescription. Despite this, nutritional support variables were formally captured in only 3 of 14 studies (21%), and no study linked dietary intake or nutritional programme participation to post-discontinuation weight trajectories. Where lifestyle support was delivered, including within NHS specialist weight management services, it was not quantified, precluding cost-effectiveness evaluation.
CONCLUSIONS: Post-discontinuation weight regain drives measurable treatment reinitiation in real-world populations, yet the nutritional determinants of this cycle remain poorly characterised in available datasets. Routine incorporation of dietary and nutritional variables into RWD collection is essential to enable cost-effectiveness modelling of integrated weight maintenance strategies and inform payer decision-making.