SURMOUNT-1 analysis shows most slow starters still succeed on tirzepatide

A post hoc analysis of the SURMOUNT-1 trial, the study that supported approval of tirzepatide (sold as Zepbound for weight management and Mounjaro for type 2 diabetes), looked at what happens to people who lose weight slowly in the first three months of treatment.^[1] Researchers followed 1,545 participants who took at least 75% of their assigned doses and had weight checks at weeks 0, 12, 24 and 72.^[1]

Of that group, 278 people, or 18%, lost less than 5% of their body weight by week 12 and were classified as "late responders." The remaining 1,267, or 82%, hit that 5% mark early and were called "early responders."^[1] At the start of the study, late responders were more likely to be male (45% versus 30%) and had higher average body weight (110.2 kg versus 103.6 kg), higher body mass index (39.1 versus 37.7 kg/m2) and larger waist circumference (117.5 cm versus 113.4 cm) than early responders.^[1]

The slow starters did not stay behind for long. By week 24, the end of the dose-titration period, 194 of the 278 late responders, or 70%, had reached 5% weight loss.^[1] By week 72, 250 of them, or 90%, had gotten there.^[1] On average, it took late responders 24.8 weeks, plus or minus 12.7 weeks, to first hit the 5% mark.^[1]

Even so, the two groups did not end up in the same place. Late responders lost an average of 11.0% of their body weight by the end of the study, compared with 22.5% for early responders, according to the trial summary.^[1] The researchers also found that higher tirzepatide doses were tied to a greater share of participants reaching various weight-loss thresholds at both week 24 and week 72.^[1]

Why it matters for patients

For people starting tirzepatide, the first three months on the drug may not predict the long-term result. The analysis suggests that a slow start in the first 12 weeks does not mean the drug is not working, since 9 out of 10 late responders eventually reached a 5% weight loss by 72 weeks by staying on treatment through dose increases.^[1]

At the same time, the data show that starting slow is linked to a smaller total loss on average. Late responders lost about 11% of body weight by the end of the study, roughly half what early responders lost.^[1] This gap could matter for people using weight loss to manage conditions like high blood pressure or joint pain, where the amount of weight lost affects the size of the health benefit.

The study also found that late responders tended to have higher starting weight, BMI and waist size, and were more often male.^[1] It is not yet known from this analysis why these groups respond more slowly, or whether other factors, such as diet, activity level or other health conditions, play a role.

What happens next

The analysis, published in Diabetes, Obesity and Metabolism, is a post hoc look at data already collected during SURMOUNT-1, not a new clinical trial.^[1] The study was funded by Eli Lilly and Company, which makes tirzepatide, and several authors are Lilly employees or have financial ties to the company or to Novo Nordisk, maker of semaglutide.^[1] The researchers say their findings support the idea that extending treatment beyond the initial 12-week period may let more patients reach meaningful weight loss, though the paper does not set out a specific timeline for when doctors or patients should reassess progress.^[1]