Introduction:
GLP-1 receptor agonists (GLP-1 RAs) like semaglutide and tirzepatide are effective for weight loss, but little is known about weight regain after their cessation. This systematic review aimed to quantify weight regain post-treatment.
Objective:
To assess how much and how quickly weight is regained following the discontinuation of GLP-1 RAs, including both traditional and newer agents.
Methods:
- Study Design: Systematic review and meta-analysis.
- Inclusion: Trials using GLP-1 RAs for ≥8 weeks in adults with overweight/obesity, reporting body weight ≥4 weeks after stopping therapy.
- Data Sources: Trial registries, databases, citation searches (up to Dec 2023).
- Analysis: Mixed and time-to-event models used to calculate monthly and annual weight regain.
Results:
|
Metric |
Any GLP-1 RA |
Newer GLP-1 RAs (Semaglutide, Tirzepatide) |
|
Weight loss at end of treatment |
7.9 kg (95% CI: 5.2–10.7) |
16.1 kg (95% CI: 11.8–20.3) |
|
Weight regain rate/month |
0.7 kg/month (95% CIs: 0.6-0.8) |
0.8 kg/month (95% CIs: 0.7-0.9) |
|
Total regain in 1 year |
8.3 kg (95% CI: 6.7–9.8) |
9.6 kg (95% CI: 7.8–11.4) |
|
Time to return to baseline weight |
0.9 years (95% CI: 0.5–1.3) |
1.7 years (95% CI: 1.1–2.3) |
|
Weight regain vs control (RCTs) |
+0.5 kg/month (95% CIs: 0.3-0.8) (p < 0.01) |
Not separately reported |
|
Time to no difference vs control |
0.8 years ((95% CIs:0.2–1.6) |
— |
Conclusion:
Stopping GLP-1 RA treatment results in rapid weight regain, with weight returning to baseline in under 2 years. Regain occurs faster than after behavioural interventions and nullifies the treatment advantage within a year. These findings highlight the need for long-term obesity management strategies alongside pharmacotherapy to sustain benefits.
ECO, 11-14 May 2025, Malaga, Spain
