Persistence with tirzepatide key to effective weight loss, study suggests

New post hoc data from Lilly's SURMOUNT-1 trial of overweight/obese people but without diabetes suggest that the drug will almost always produce at least 5% weight loss eventually, even among slow responders.

The findings presented at the American Association of Clinical Endocrinology (AACE) 2024 conference suggest patience may pay off when using tirzepatide (Zepbound, Eli Lilly) to treat obesity.

"Some obesity treatment guidelines suggest anti-obesity medication (AOM) discontinuation that fails to produce 5% or greater weight reduction within 12 weeks. Newer AOMs may take longer to achieve full weight-loss benefit given their recommended dose titration schedule," Kimberly Gudzune, MD, director of the Johns Hopkins Healthful Eating, Activity & Weight Program, Baltimore, Maryland.

The analysis showed that among participants who had lost less than 5% of their body weight by week 12 of tirzepatide, nearly all went on to lose 5% or more by week 72. Thus, Gudzune said, "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."

The post hoc analysis included 1545 patients; they were randomly assigned to total tirzepatide doses of 5 mg, 10 mg, or 15 mg, and had data available at weeks 0, 12, 24, and 72. Among those, 1267 had lost at least 5% of their body weight by week 12, defined as "early responders," and 278 had lost less than 5% of body weight by then, called "slow responders."

The study led to the following findings:

• At baseline, slow responders were significantly more likely to be male (44.8% of slow versus 30.1% of early responders), have higher body weight (24.3 kg versus 21.8 kg), and have lower waist circumference (117.5 cm versus 113.4 cm).
• There were no significant differences by age, body mass index, prediabetes status, or obesity duration.
• By the end of dose titration at week 24, 70% of slow responders had achieved 5% or more of body weight reduction, as had 100% of early responders.
• By 72 weeks, 90% of the slow responders had achieved at least 5% of body weight loss, and 30% had achieved at least 15% reduction.
• Even in the group maintained on the lowest 5-mg dose throughout the trial, 87% had achieved at least 5% weight loss by week 72, with 15% achieving at least 15%. And in the group that had been titrated up to 15 mg tirzepatide, 94% of slow responders achieved at least 5% weight loss.
• The mean time to reach 5% weight loss for slow responders who went to achieve 5% or greater weight loss was 24.8 weeks.
• Of the total 1545 participants, there were 28 who had lost less than 5% of their overall body weight on tirzepatide. Of those, four had missed more than three consecutive doses, and 13 were on the lowest 5-mg dose.

"Future studies are warranted for better understanding the variability in weight loss response to tirzepatide treatment," the researchers concluded.