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TOPLINE:

Mathematical modeling of tirzepatide treatment showed substantial early weight loss that later leveled off as calorie intake increased and energy expenditure reduced. GLP-1 discontinuation was followed by partial weight regain.

METHODOLOGY:

• Treatment with GLP-1 receptor agonists induces substantial early weight loss but often results in prolonged plateaus. The underlying changes in energy dynamics remain unclear.
• Researchers applied a human metabolism mathematical model to published data from the SURMOUNT-1 trial to estimate weight loss, energy intake, and energy expenditure during tirzepatide treatment.
• They modeled a representative participant — a 48-year-old sedentary woman (weight, 108 kg; BMI, 40) — using aggregated data from the treatment arm of the trial. The participant was modeled to receive 15 mg tirzepatide weekly for 176 weeks and to experience a 17-week off-treatment period thereafter.
• Data on mean percent weight change and SDs were extracted from the trial, and the Hall model was used to estimate daily energy intake and expenditure from weight and body composition changes.
• Uncertainty was quantified by running 1000 Monte Carlo iterations that sampled percent weight change at each reported timepoint.

TAKEAWAY:

• Weight loss peaked at 24.0% by week 96, corresponding to a reduction from 108 kg to 82.9 kg. The weight remained stable for about 78 weeks despite continued weekly tirzepatide, with minimal further loss between weeks 96 and 176.
• After tirzepatide was discontinued at week 176, the model predicted a 5.7-kg regain over the next 17 weeks, with weight increasing to 88.6 kg and weight loss decreasing to about 18%.
• Energy intake decreased by about 32.1% during the first 4 weeks (from 2761 kcal/d to about 1875 kcal/d) and subsequently increased to 2500 kcal/d by week 98, matching energy expenditure.
• Energy expenditure dropped by about 9.2% by week 98 (to about 2509 kcal/d), stabilized through week 176, and subsequently increased to 2558 kcal/d by week 193.

IN PRACTICE:

“While further research is needed, these findings support a role for GLP-1 receptor agonists not only as induction agents but also as components of long-term maintenance framework integrated with lifestyle strategies,” the authors of the study wrote.

SOURCE:

The study was led by Patrice A. Hubert, PhD, Medifast, Inc., Baltimore. It was published online in the Journal of the Academy of Nutrition and Dietetics.

LIMITATIONS:

The study used only published aggregate data on weight change; thus, losses to follow-up and issues of missing data could not be assessed. The model was run on a single representative person, which may not have captured individual differences in response, adherence, or dose changes. The model assumed constant activity and a middle-aged female profile, limiting generalizability.

DISCLOSURES:

The study did not receive any external funding and was supported internally by the authors’ institution. Five authors reported being employees of Medifast, Inc., which develops and markets weight management programs. Four authors reported serving as members of the Scientific Advisory Board of Medifast. Another author reported being an employee of WHOOP, Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.