SURMOUNT-4: trial summary, limitations and UK relevance

Key findings

SURMOUNT-4 established the randomised-withdrawal signal for tirzepatide: after 36 weeks of open-label tirzepatide, participants continued on active therapy preserved substantially more of the prior weight reduction than those withdrawn to placebo across the following 52 weeks. Placebo-withdrawal participants regained a substantial proportion of the initial weight loss — consistent with the parallel STEP-4 (semaglutide) signal — while continuation participants maintained or extended their weight-reduction trajectory. The finding directly informs the clinical framing of GLP-1 / dual-agonist therapy as ongoing rather than time-limited: stopping the drug reverses much of the effect within a year. It does not, however, characterise longer discontinuation or tapered-discontinuation scenarios. For precise numerical results consult the JAMA 2024 publication.

Safety summary

GI events remained the dominant adverse event class. Withdrawal arm safety profile reflected the absence of active therapy.

Limitations

• Randomised-withdrawal design — generalisability is to those who tolerate and respond during the lead-in.
• Cannot fully characterise sustainability beyond the trial period.

UK relevance

Directly informs the UK clinical question of weight regain after discontinuation of incretin therapy — a relevant consideration for NHS specialist weight-management programmes and post-treatment planning.