Michael Monostra , 2025-04-22 13:05:00
April 22, 2025
4 min read
Key takeaways:
- Adults with obesity and prediabetes had a mean weight regain of 3.7% at 176 weeks after reaching their nadir weight loss.
- Response to tirzepatide may vary based on weight-loss trajectory.
Editor’s note: Full data from this research will be presented at the European Congress on Obesity in May.
Adults with overweight or obesity plus prediabetes maintain most of their weight loss with tirzepatide at more than 3 years, according to data from two European Congress on Obesity abstracts.
Data were derived from Aronne LJ, et al. Abstract 46. To be presented at: European Congress on Obesity, May 11-14, 2025; Malaga, Spain.
As Healio previously reported, the SURMOUNT-1 3-year trial assessed the efficacy of tirzepatide (Mounjaro/Zepbound, Eli Lilly) on body weight and glycemia for adults with prediabetes who participated in SURMOUNT-1. Of adults with prediabetes receiving tirzepatide who lost at least 5% of their body weight, up to 96% had a reversion to normoglycemia at 176 weeks vs. 83% of those receiving placebo.
In two post hoc analyses of the SURMOUNT-1 3-year trial, researchers found most adults with prediabetes had a weight regain of less than 5% after reaching their nadir weight during the study. Researchers also presented data on weight-loss trajectories with tirzepatide that may help inform clinical practice, according to Luca Busetto, PhD, professor of nutrition in the department of medicine at University of Padova in Italy.
Luca Busetto
“These results could help clinicians in understanding at an early stage of treatment what will be the final weight that can be reasonably achieved,” Busetto told Healio. “This is important in identifying early patients that could require a more intensive intervention.”
Most weight loss retained long term
In the first post hoc analysis, researchers assessed data from 690 participants in the SURMOUNT-1 3-year study who lost at least 5% of their body weight (mean age, 49 years; mean baseline BMI 38.6 kg/m2). Weight regain was assessed from the point nadir weight loss to 176 weeks.
The study group reached a mean nadir weight loss of 23.1% in a mean of 22 months. At 176 weeks, participants had a weight regain of 3.7%. The mean weight loss for the participants at 176 weeks was 19.4%.
Louis J. Aronne
Of adults receiving 5 mg tirzepatide, 73% regained less than 5% of their body weight after reaching nadir, 19% regained between 5% and 10% of their weight and 8% had a weight regain of 10% or higher. Of those using 10 mg tirzepatide, 65% had a weight regain of less than 5%, 26% regained between 5% and 10% of their weight and 9% regained 10% or more of their body weight. Of adults receiving 15 mg tirzepatide, 73% regained less than 5% of their weight, 20% had a weight regain between 5% and 10%, and 7% regained 10% or more of their weight.
“The fact that there was weight regain in some people, even though they were taking the medication demonstrates how the weight-regulating pathways are constantly trying to get people to regain the weight they lose,” Louis J. Aronne, MD, FACP, FTOS, DABOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine in New York and lead author of the post hoc analysis, told Healio.
Aronne said the findings were unsurprising after results from the primary analysis of the SURMOUNT-1 3-year study showed losing at least 5% body weight with tirzepatide prevented the development of type 2 diabetes for most participants. He said more long-term outcome studies are underway that could reveal additional benefits in the future.
“It’s possible to maintain the majority of weight loss over at least 3 years using the new, highly effective obesity medications,” Aronne said. “This will lead to much better health.”
Weight-loss patterns vary
In the second post hoc analysis, researchers assessed data from 700 adults in the SURMOUNT-1 3-year trial. Adults were placed into one of three weight-loss trajectory groups based on percent weight change and time to reach a weight loss of 20%. Participants were considered to have reached a weight plateau when they had less than 5% weight change over a 3-month period after initial weight loss.
Of the study participants, 248 adults were placed in the first group, which had a steady early weight loss and early weight plateau. The first group had the lowest mean weight loss of 9.2% at 176 weeks. There were 226 participants placed in the second group with a faster early weight reduction and later weight plateau than group one. Adults in group two had a mean 20.2% weight loss at 176 weeks. The remaining 226 participants were placed in group three with a faster weight loss and later weight reduction plateau than the other two groups. Mean weight loss was highest in the third group at 30.8%.
“We do not yet have a clear understanding about the mechanisms behind these different weight-loss trajectories,” Busetto said. “At first look, women and patients without obesity-related complications seem to do better.”
At the end of the study, group three had a lower percentage of participants reach their body weight plateau (81.4%) than group one (87.1%) and group two (87.6%). At 24 weeks, 74.5% of group one, 48% of group two and 17.4% of group three reached their body weight plateau. Of the participants in group three, 82.7% reached their weight plateau at either 36 or 48 weeks.
Busetto said future studies should examine the mechanisms supporting different weight-loss trajectories.
Reference:
- Busetto L, et al. Abstract 105. To be presented at: European Congress on Obesity, May 11-14, 2025; Malaga, Spain.
For more information:
Louis J. Aronne, MD, FACP, FTOS, DABOM, can be reached at ljaronne@med.cornell.edu or on X @ljaronne.
Luca Busetto, PhD, can be reached at endocrinology@healio.com.
Sources/Disclosures
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Aronne LJ, et al. Abstract 46. To be presented at: European Congress on Obesity, May 11-14, 2025; Malaga, Spain.
Disclosures:
Aronne reports receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences and Versanis; and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth and Jamieson Wellness. Busetto reports advising or speaking for Boehringer Ingelheim, Bruno Farmaceutici, Eli Lilly, Novo Nordisk, Pfizer, Pronokal, Regeneron and Rhythm Pharmaceuticals.
