Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 40186344 · doi:10.1111/obr.13929
What was done
Authors conducted a systematic review and meta-analysis across multiple databases (MEDLINE, Cochrane Central, PubMed, CINAHL, Academic Search Premier) through February 1, 2024. They evaluated randomized controlled trials (RCTs) assessing body habitus outcomes (body weight, waist circumference, and BMI) on and off glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in adults with BMI ≥ 27 kg/m². Pooled mean differences were calculated using a DerSimonian-Laird random-effects model across 8 included RCTs comprising 2,372 participants.
What was found
Following discontinuation of GLP-1RA treatment, weight regain occurred in proportion to initial weight loss. Discontinuing liraglutide led to a significant mean weight regain of 2.20 kg (95% CI: 1.69 to 2.70 kg, P < 0.00001). Discontinuing semaglutide or tirzepatide resulted in a mean weight regain of 9.69 kg (95% CI: 5.78 to 13.60 kg, P < 0.00001). Specific numerical values for off-treatment changes in waist circumference and BMI were not reported in the abstract.
Why it matters
These findings indicate that weight loss achieved via GLP-1RA therapy is not maintained following drug cessation. This reinforces that obesity pharmacotherapy functions as a chronic, long-term intervention rather than a temporary cure.
Limits
The meta-analysis included only 8 RCTs and combined semaglutide with tirzepatide (a dual GIP/GLP-1 receptor agonist) rather than analyzing them separately. The abstract does not specify off-treatment follow-up durations, background lifestyle interventions, or changes in body composition (fat versus lean mass).
Cited by
- context Studies show that newer GLP-1 receptor agonists like semaglutide cause more rapid and excessive weight regain after discontinuation compared to older agents like liraglutide and exenatide.