Behavioral modifications like goal setting could lead to greater weight loss on tirzepatide: Study

One of the largest real-world studies of people taking GLP-1 medications found women, those without pre-existing conditions such as type 2 diabetes and high blood pressure, and behavioral factors such as previously setting a weight goal were the best predictors of total weight loss, according to a study being presented Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

The scientists believe the findings could help doctors personalize treatment options for weight management.

The research was a collaborative effort between Voy (Menwell Ltd.), a digital health service based in London, United Kingdom, and the Predictive Medicine Group at Boston Children's Hospital and Harvard Medical School in Boston, Mass. The study occurred February 2024 through November 2025 and involved more than 80,000 adults using tirzepatide, a medication sold commercially as Mounjaro and Zepbound. The scientists designed the study to find out why the amount of weight individuals lost tended to vary significantly.

"It is one of the largest real-world studies of tirzepatide to date and is the first to identify behavioral and clinical predictors that anticipate who will respond best to the medication," said Hans Johnson, M.B.Ch.B, M.Res., F.R.S.P.H., research lead in the Department of Clinical Research and Innovation at Voy.

Johnson and his colleagues used Cox proportional hazards models to determine the time needed to achieve 20% total body weight loss. They also employed multivariate mixed models to find associations between baseline clinical, demographic, and behavioral variables and weight loss trajectories over 12 months.

The team found that women tended to lose more weight on tirzepatide than men and that pre-existing conditions such as type 2 diabetes, high cholesterol, hypertension, metabolic liver disease, and obstructive sleep apnea were associated with less weight loss. Based on the mixed models, the researchers established that behavioral factors, like setting a personal weight goal or having previously attempted structured diets, were associated with significantly greater weight loss. In contrast, participants who lacked the self-motivation to lose weight experienced minimal weight loss on the medication.

"These findings could help physicians better counsel patients about realistic expectations and tailor their support to the needs of each patient," Johnson said. "For example, doctors could ensure patients with motivational barriers to losing weight receive additional behavioral interventions alongside their medication."

Reference:

Behavioral modifications like goal setting could lead to greater weight loss on tirzepatide, The Endocrine Society, Meeting: ENDO 2026.