What question did this study set out to answer?

This research aims to evaluate changes in body composition and metabolic outcomes during and after tirzepatide treatment for obesity.

June 7, 2026

1676-P: Changes in Body Composition During and After Weight Loss with Tirzepatide

Key Points

This research aims to evaluate changes in body composition and metabolic outcomes during and after tirzepatide treatment for obesity.
Adults with obesity (n=63) were randomized to 22 weeks of tirzepatide or dietary weight loss.
A subset of tirzepatide-treated participants (n=13) completed a 4-month off-treatment follow-up.
Body composition and insulin resistance were assessed using DXA scans and steady-state plasma glucose testing.
Tirzepatide treatment led to a mean weight reduction of 12.5 kg (14% of baseline weight) with 40% of this being lean mass loss.
Insulin sensitivity improved by 60% during treatment but showed 42% reversal post-treatment.
Most regained weight was lean mass (67%) with increased subcutaneous fat (34%) compared to visceral fat (7.5%).

Abstract

Introduction and Objective: Tirzepatide induces substantial weight loss, lean mass loss, and metabolic improvement, but durability after discontinuation is unclear. Whether post-treatment weight regain reflects fat vs muscle or visceral vs subcutaneous fat is unknown. We evaluated changes in body composition, regional fat, and metabolic outcomes during and after therapy. Methods: Adults with obesity (n=63; BMI 32.2 kg/m²) were randomized to 22 wks of tirzepatide or dietary weight loss. A subset of tirzepatide-treated participants completed a 4-month off-treatment follow-up (n=13). Assessments included anthropometrics, DXA-derived whole-body and regional composition, and insulin resistance measured by steady-state plasma glucose testing. Results: Tirzepatide treatment resulted in a mean weight reduction of 12.5 kg (14%) of baseline weight, with lean mass accounting for 40% of total weight loss. Insulin sensitivity improved by 60% during treatment. After medication withdrawal, weight and insulin sensitivity both showed 42% reversal. Regained weight consisted mainly of lean mass (67%) compared to fat mass (38%). Regained fat preferentially accumulated in the subcutaneous (34%) over visceral (7.5%) fat depot, with a reduced android-to-gynoid fat ratio. Conclusion: Weight regain after tirzepatide discontinuation does not appear to adversely affect lean-to-fat mass balance or regional fat distribution. However, metabolic benefits during active treatment were only partially sustained. Disclosure E. Yandle: None. T. McLaughlin: Research Support; Ended; Lilly. Advisory Panel; Ended; Regeneron Pharmaceuticals Inc. Research Support; Current; Recordati S.p.A. Stock/Shareholder; Current; January, Inc. Research Support; Current; WW International, Inc. Consultant; Ended; Eiger BioPharmaceuticals. Advisory Panel; Current; Amylyx. Consultant; Current; Oura. Research Support; Current; Dexcom, Inc. C. Johnston: None. J. Yang: None. N. Turk: None. H. Chen: None. D. Perelman: None. Funding National Institutes of Health (P30DK116074), Stanford Diabetes Research Center, Eli Lilly and Company, IIR Research (Submission ID: 75589)

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