Slow Responders to Zepbound Achieve Meaningful Weight Loss Eventually

NEW ORLEANS — The vast majority of patients with obesity who responded slowly to the once-weekly injectable tirzepatide (Zepbound) achieved meaningful reductions in body weight a year later, a post hoc analysis of the SURMOUNT-1 trial showed.

In study participants who failed to shed 5% of their body weight at 12 weeks, more than 90% ultimately achieved that clinically meaningful level of weight loss at 72 weeks, with 30% dropping at least 15% of their body weight, reported Kimberly Gudzune, MD, of Johns Hopkins School of Medicine in Baltimore.

“It is reasonable to consider treatment for longer than 12 weeks to determine weight-loss response to tirzepatide, which takes at least 20 weeks to reach the highest dose,” said Gudzune, who presented the findings here at the American Association of Clinical Endocrinology annual meeting.

By 24 weeks, 70% of the slow responders lost at least 5% of their body weight, and that included 8% who lost 10% or more of their weight, and 1% who lost 15% or more.

Guidelines suggest switching weight-loss medications if a 5% reduction in body weight isn’t achieved at 12 weeks, noted session moderator Capt. Thanh Hoang, DO, of Walter Reed National Military Medical Center in Bethesda, Maryland.

But “the old saw ‘if at first you don’t succeed, try, try again’ might be apt in the setting of the newer anti-obesity medications” such as tirzepatide and semaglutide (Wegovy), he told MedPage Today.

“If I had a patient on tirzepatide who was making some progress on tirzepatide, I would continue that patient until I had gone through the full titration regimen,” said Hoang, who was not involved in the study. “But if there was no substantial progress after 6 months, I would likely stop that treatment.”

SURMOUNT-1 was part of the trial program that led to the FDA approval of tirzepatide — a combination glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist — for treating obesity. (The drug was first approved in 2022 for type 2 diabetes under the brand name Mounjaro.) High demand for the weight-loss formulation of tirzepatide has already led to shortages.

The primary results of SURMOUNT-1 showed that people taking the highest dose (15 mg) of the once-weekly injectable lost an average 22.5% of their body weight at 72 weeks, with lower doses also demonstrating weight reductions of 16% (5-mg) and 21.4% (10-mg).

The post-hoc analysis presented by Gudzune focused on the patients in SURMOUNT-1 who were adherent to tirzepatide (received 75% of doses) and had weight measurement data at weeks 0, 12, 24, and 72. These included 278 patients who failed to achieve a 5% weight-loss reduction at 12 weeks with the drug (slow responders) and 1,267 individuals who did (early responders).

For inclusion in the study, participants had to have obesity (BMI ≥30) or be overweight (BMI ≥27) with at least one weight-related condition. Patients were assigned to maximum doses of 5 mg, 10 mg, or 15 mg, with each initially starting at a 2.5-mg dose. Patients assigned to 5 mg as the highest dose switched to that dose level at 4 weeks. Those assigned to 10 mg switched to 5 mg at 4 weeks, 7.5 mg at 8 weeks, and then 10 mg at 12 weeks. Patients assigned to the highest dose level (15 mg) followed that same schedule but switched to 12.5 mg at 16 weeks, and then 15 mg at 20 weeks.

At baseline, the slow responders tended to be older compared with the early responders (46.7 vs 45 years), were more likely to be men (44.6% vs 30.6%), weighed more (110.2 vs 103.6 kg), had a higher BMI (39.1 vs 37.7), and had a larger waist circumference (117.5 vs 113.4 cm, P<0.05 for all).

Mean time to reach a 5% weight loss was 24.8 weeks for the slow responders, and 12.7 weeks for the early responders, said Gudzune.

At 72 weeks, slow responders had lower rates of weight-loss compared with the early responders:

• ≥5% weight loss: 90% vs 100%, respectively
• ≥10% weight loss: 59% vs 97%
• ≥15% weight loss: 30% vs 84%
• ≥20% weight loss: 17% vs 65%
• ≥25% weight loss: 7% vs 41%

In her conclusion, Gudzune said that “future studies are warranted to better understand the variability in weight-loss response to tirzepatide treatment.”

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