Design: systematic review and meta-analysis of 6 randomised and controlled trials, Cochrane RoB 2.0
Population: 8,993 overweight or obese adults - 5,553 discontinuing a GLP-1 receptor agonist, 3,440 continuing
Primary outcome: weight change after discontinuation
Effect: 17.90% difference versus continued treatment (95% CI 14.11-21.69); 9.11% regain from pre-withdrawal weight (7.91-10.30); larger after tirzepatide than semaglutide

Six studies with 8,993 patients - 5,553 who discontinued a GLP-1 receptor agonist and 3,440 who continued - were pooled to quantify what happens after withdrawal. Compared with continued treatment, the discontinuation group differed by 17.90% in weight (95% CI 14.11 to 21.69, p<0.0001), with statistical heterogeneity between studies. Comparing weight after withdrawal against weight before it in the same patients gave 9.11% (7.91 to 10.30). Subgroup analysis found rebound after tirzepatide larger than after semaglutide. Adverse events, particularly gastrointestinal ones, fell after stopping; cardiovascular event rates were unaffected.

None of this is surprising and all of it is worth quantifying, because the conversation with the patient at the point of prescribing is where it belongs. These are agents for a chronic condition, and stopping them behaves like stopping an antihypertensive: the effect goes with the drug.

For hepatology the relevance is now direct. Semaglutide has conditional approval in MASH with F2-F3 fibrosis, and the fibrosis benefit was demonstrated on treatment. What happens to liver histology after withdrawal has not been established, and a patient who regains 9% of body weight is unlikely to be holding a histological gain. Cost and supply in Indian practice make unplanned discontinuation common rather than exceptional, which makes this a conversation to have at initiation, not at the point the patient runs out.

Say at initiation that stopping means regaining - these are chronic treatments, not courses
Plan for cost and supply interruptions explicitly rather than treating them as unexpected
Intensify diet, activity and behavioural support around any planned stop rather than after regain
Do not assume a fibrosis benefit persists after discontinuation - it has not been studied
Reassure patients that gastrointestinal side effects settle after stopping; that is the one clear upside

Why it matters

It puts a number on the consequence of the interruptions that cost and supply already impose on most patients taking these drugs.

The statistics, in plain English

Two different numbers here answer two different questions. The 17.9% is the gap that opens between people who stopped and people who carried on, which combines regain in one group with continued loss in the other. The 9.11% is the regain within the people who stopped, and that is the figure to quote to a patient. Heterogeneity was statistically significant, and with six studies of differing agents, doses and follow-up lengths, the pooled magnitude should be treated as approximate. The tirzepatide-versus-semaglutide difference is a subgroup comparison and hypothesis-generating.