Analysis defines when tirzepatide weight loss plateaus

A post hoc analysis of two major tirzepatide trials has pinned down when weight loss typically stops progressing and levels off, information that could help patients and doctors set realistic expectations during treatment ^[1].

Researchers looked at data from SURMOUNT-1 and SURMOUNT-4, two clinical trials of tirzepatide, the drug sold as Mounjaro and Zepbound, in people with obesity or overweight ^[1]. The study included 1,438 participants from SURMOUNT-1 and 259 from SURMOUNT-4 who stuck with tirzepatide treatment and lost at least 5% of their body weight by the trial's main measurement point, which was week 72 in SURMOUNT-1 and week 88 in SURMOUNT-4 ^[1]. A weight plateau was defined as a change of less than 5% over a 12-week stretch, with that pattern holding for all following 12-week periods ^[1].

The median time to reach a plateau varied depending on starting body mass index. In SURMOUNT-1, people classified as having overweight hit a median plateau at 24.3 weeks, while those with class I obesity plateaued at 26.0 weeks ^[1]. People with class II or class III obesity took longer, plateauing at a median of 36.1 weeks for both groups, a statistically significant difference compared with the overweight group ^[1]. By week 72, the large majority of participants across all these groups had reached a plateau, ranging from 87.6% to 90.2% ^[1]. Results in SURMOUNT-4 were described as similar ^[1].

The analysis also identified factors linked to a later plateau. People taking higher doses of tirzepatide, 10 mg or 15 mg, were more likely to keep losing weight for longer before leveling off, as were younger participants and women ^[1]. The paper notes this pattern was consistent between the two trials ^[1].

Why it matters for patients

Weight loss on tirzepatide, like other GLP-1 based treatments, does not continue indefinitely at the same pace. This analysis suggests that for most people, meaningful further weight loss slows or stops somewhere between roughly six months and nine months after starting the drug, depending on individual factors ^[1]. Knowing this timeline in advance could help patients avoid mistaking a plateau for a sign that the medication has stopped working, since a plateau still represents maintained weight loss rather than a return to baseline weight ^[1].

The finding that higher doses, younger age and female sex were linked to later plateaus points to real variability in how the drug behaves in different people ^[1]. This means the study's overall averages may not describe any single patient's experience closely, since factors like starting body size, dose level, age and sex all appeared to shift the timeline ^[1].

The study's authors, several of whom are employees and shareholders of Eli Lilly and Company, the maker of tirzepatide, say the findings could inform treatment decisions for people using the drug for long-term weight management ^[1]. It's also worth noting that this was a post hoc analysis, meaning researchers examined the trial data after the fact to answer a question the original studies were not specifically designed to test ^[1].

What happens next

The study's authors call for further research into what drives these different phases of weight loss with tirzepatide, saying this could help refine how the drug is used for chronic weight management going forward ^[1]. No specific timeline or follow-up study is mentioned in the available material ^[1].