Analysis: slow starters on tirzepatide often still reach 5% weight loss by week 72

A post hoc analysis of the SURMOUNT-1 trial found that 90% of participants who lost less than 5% of their body weight in the first 12 weeks of tirzepatide treatment reached at least 5% weight loss by week 72 ^[1]. Tirzepatide is the molecule in Mounjaro and Zepbound.

The analysis, published in the journal Diabetes, Obesity and Metabolism, sorted 1,545 trial participants by how quickly they responded ^[1]. All had received at least 75% of their assigned doses and had their weight measured at weeks 0, 12, 24 and 72. Of those, 278 (18%) were classified as late responders, meaning they had lost less than 5% of body weight by week 12, and 1,267 (82%) were early responders, meaning they had lost 5% or more by then ^[1].

At the start, late responders differed from early responders in several ways. They were more likely to be male (45% versus 30%) and had higher average body weight (110.2 kg versus 103.6 kg), body mass index (39.1 versus 37.7 kg/m2) and waist circumference (117.5 cm versus 113.4 cm) ^[1].

Among late responders, 194 (70%) had reached at least 5% weight loss by week 24, at the end of dose titration, and 250 (90%) had reached it by week 72 ^[1]. The average time for a late responder to reach 5% weight loss was 24.8 weeks, with a standard deviation of 12.7 weeks ^[1]. Higher doses of tirzepatide were associated with higher proportions of participants reaching the various weight-loss thresholds at weeks 24 and 72 ^[1].

The analysis reports that late responders lost an average of 11.0% of their body weight in total, compared with 22.5% for early responders ^[1]. The authors conclude that extending treatment well beyond 12 weeks may allow more patients to achieve what they describe as clinically meaningful weight reduction ^[1].

Some limits apply. This was a post hoc analysis, so the two groups were defined after the trial was under way rather than by random assignment, and it included only participants who took most of their doses and had weight recorded at all four time points, so the results may not describe everyone who starts tirzepatide ^[1]. The paper credits Eli Lilly and Company in its copyright line, and six of the listed authors are employees and shareholders of Eli Lilly, which makes tirzepatide ^[1]. SURMOUNT-1 is registered on ClinicalTrials.gov as NCT04184622 ^[1]. Whether the same pattern holds for other weight-loss drugs, including semaglutide (Ozempic, Wegovy, Rybelsus) or orforglipron (Foundayo), has not been reported.

Why it matters for patients

The three-month mark is a point when patients and their doctors often take stock of whether a GLP-1 medication is working. This analysis addresses that question directly: among people who had lost little by week 12 but stayed on tirzepatide, 90% eventually crossed the 5% threshold ^[1].

At the same time, the late responders did not catch up to the early responders. Their average total loss was about half as large, 11.0% versus 22.5% of body weight ^[1]. So a slow start did not mean the drug failed, but it did track with a smaller overall result in this group.

The analysis does not identify in advance who will be a late responder, and it offers no rule for deciding when to wait and when to change treatment. It also does not report whether late responders had more side effects, whether their doses were adjusted differently, or how many people who lost less than 5% by week 12 would have reached that threshold had they stayed on placebo instead. Those questions have not been answered here ^[1].

One number worth keeping in context: the 5% threshold used throughout the analysis is the same one the authors call clinically meaningful, and it is well below the 20% or greater losses reported for some participants at week 72 in the figures accompanying the paper ^[1].