Tirzepatide trial subgroup lost weight after starting medicines linked with weight gain

What happened

A post hoc analysis of three SURMOUNT trials examined participants who began taking at least one medicine associated with weight gain while enrolled. Tirzepatide-treated participants in these subgroups continued to show substantial weight reduction relative to the relevant placebo groups.

The analysis drew from SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4. It included 442 participants from the first trial, 100 from the second, and 134 from the third. These subgroups represented 17.4%, 17.3%, and 20.0% of the respective trial populations.

Most qualifying medicines required at least three months of use, while oral corticosteroids required one week. Follow-up ended at 72 weeks in the first and third SURMOUNT studies and at 88 weeks in the fourth study.

In SURMOUNT-1, estimated tirzepatide-placebo differences in weight change among subgroup members ranged from 13.3 percentage points at the 5 mg dose to 21.3 points at 15 mg. The difference was 26.1 points in SURMOUNT-3, which used the highest tolerated dose, and 18.6 points in SURMOUNT-4.

The efficacy analysis used measurements collected while participants remained on tirzepatide. Data after treatment discontinuation were excluded. The researchers concluded that weight reductions in these subgroups were comparable with the parent trials' main findings.

What it means

Medicines that can contribute to weight gain may still be necessary for psychiatric, inflammatory, neurologic, or other medical conditions. This analysis offers some evidence that starting one of the specified drugs did not erase the weight reduction observed with tirzepatide during the trial period.

The finding is most useful as a signal for further study. It comes from randomized tirzepatide trials, but the decision to start a weight-promoting medicine was not itself randomized. Participants who needed those medicines may differ from other trial participants in ways the analysis could not fully address.

What it does not mean

The results do not show that tirzepatide cancels out every medicine-related weight effect. The analysis covered a prespecified list and required minimum exposure periods. It did not compare every drug, dose, indication, or combination separately.

These subgroup findings do not justify stopping an important medicine or adding tirzepatide solely to offset expected weight gain. They also do not establish what happens after tirzepatide is discontinued, because the efficacy analysis omitted later measurements.

The work was a post hoc analysis rather than a trial designed around concomitant medications. Eli Lilly sponsored the SURMOUNT program, and the article's disclosures include company relationships. The results need confirmation in studies built to answer this specific question.