Most ‘slow responders’ to tirzepatide achieve 5% or greater weight reduction at 72 weeks


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Key takeaways:

  • Of adults who did not lose 5% of their weight with tirzepatide at 12 weeks, 90% achieved 5% weight loss at 72 weeks.
  • By the end of SURMOUNT-1, 30% of the slow responders group lost 15% or more body weight.

NEW ORLEANS — Nearly all adults who lose less than 5% of their body weight with tirzepatide at 12 weeks were able to achieve at least a 5% weight loss by 72 weeks, according to a post-hoc analysis of the SURMOUNT-1 trial.

As Healio previously reported, adults with obesity or overweight with at least one weight-related comorbidity lost up to 20.9% of their body weight at 72 weeks with tirzepatide (Zepbound, Eli Lilly) in SURMOUNT-1. However, some adults were unable to achieve a 5% or greater weight loss in the first 12 weeks of the trial.



Nine out of 10 slow responders to tirzepatide lose 5% or more body weight at 72 weeks.

Data were derived from Gudzune K, et al. Weight reduction over time in tirzepatide-treated participants by early weight loss response – post-hoc analysis in SURMOUNT-1. Presented at: American Association of Clinical Endocrinology Annual Scientific and Clinical Conference; May 9-11, 2024; New Orleans.

“Some obesity treatment guidelines actually suggest that we consider the efficacy of our treatment response at 12 weeks, and if a patient isn’t having a response, to actually discontinue treatment and try another strategy,” Kimberly Gudzune, MD, MPH, associate professor of medicine at the Johns Hopkins University School of Medicine and medical director at the American Board of Obesity Medicine, said during a presentation at the AACE annual meeting. “While that was great with some of the older anti-obesity medications, now with some of the newer anti-obesity medications, it may actually take a little bit longer to really determine whether they are achieving their full benefit.”

In SURMOUNT-1, adults with overweight or obesity and without diabetes were randomly assigned to receive 5 mg, 10 mg or 15 mg of tirzepatide or placebo for 72 weeks. The post-hoc analysis included 1,545 adults in SURMOUNT-1 who took at least 75% of the doses they received and had weight measurements available at baseline, 12 weeks, 24 weeks and 72 weeks. Participants were placed into a slow responders group if they lost less than 5% of their baseline body weight at week 12, or into an early responders group if they achieved a 5% or greater weight loss at 12 weeks.

There were 278 slow responders (mean age, 46.7 years; 44.6% men) and 1,267 early responders (mean age, 45 years; 30.1% men) in the study. The slow responders had a higher baseline body weight and waist circumference than the early responders.

At 24 weeks, 70% of the slow responders achieved a 5% or greater weight reduction, and 8% lost 10% or more body weight. At 72 weeks, 90% of the slow responders lost 5% or more body weight, 59% achieved a 10% or greater weight loss and 30% lost at least 15% of their body weight. A 5% or greater weight reduction at 72 weeks was achieved by most participants across all three tirzepatide dose groups.

The mean time to reach a 5% weight loss for the slow responders was 24.8 weeks. Of adults who did not lose 5% of their body weight at 72 weeks, four had missed more than three consecutive doses of tirzepatide. Among those who did not lose at least 5% of their body weight, 13 received the 5 mg dose, nine received the 10 mg dose and six received the 15 mg dose.

One reasons for the slow response may be tied to the dose titration schedule, according to Gudzune. In SURMOUNT-1, the 10 mg group reached the maximum dose at 12 weeks, and the 15 mg group did not reach the maximum dose until 20 weeks.

“One of the take-home thoughts is it’s reasonable to consider treatment for longer than 12 weeks to determine weight loss response with this medication, particularly because it takes up to 20 weeks to reach the highest dose,” Gudzune said.

Gudzune added that more studies are needed to better understand weight loss variability with tirzepatide.

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