Withdrawal and follow-up
Weight after tirzepatide withdrawal
The returning total gives the word loss a second complication: how long the change lasts.
Continuation in SURMOUNT-4
SURMOUNT-4 randomized adults with obesity after a 36-week open-label tirzepatide lead-in. From week 36 to week 88, mean weight change was −5.5% with continued tirzepatide versus +14.0% with placebo. Before randomization, the lead-in had produced a mean 20.9% weight reduction.
The starting point of that comparison is week 36. It comes after the lead-in. The choice that follows is consequential: people already receiving the treatment either continue it or switch to placebo. The subsequent weight changes point in different directions.
I resist turning regain into a verdict on the people who experienced it. The randomized comparison gives treatment continuation a central role in the result.
Cardiometabolic changes with regain
A post hoc SURMOUNT-4 analysis followed adults with obesity who switched to placebo after tirzepatide. Greater weight regain was associated with larger increases in waist circumference, systolic blood pressure, non-HDL cholesterol, HbA1c and fasting insulin. This was an association examined after the main trial.
That adds a second dimension to the returning weight. My concern extends to the changes in those health-related measures. The association offers a reason to examine maintenance more closely; it does not allocate the returning weight between fat and lean tissue.
For comparison, the separate semaglutide STEP 5 trial found sustained mean weight reduction over 104 weeks, significantly greater than placebo, in adults with overweight or obesity. Treatment and withdrawal are different circumstances, and these are also different medicines and studies.
The composition of regain
The tirzepatide body-composition finding during weight reduction described losses of fat and lean mass. The withdrawal trial gives a result for returning total weight. I’m left asking which tissues make up that returning total, and how physical ability changes during the return.
Those are open questions here. Allocating that regain between fat and lean tissue would outrun the findings available here. The missing allocation returns the argument to its starting question: what came off?
Treatment burden adds another reason to think carefully about the circumstances in which a result can be sustained.