Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes

Abstract

Objective: To evaluate the effects of tirzepatide on body composition, appetite, and energy intake to address the potential mechanisms involved in body weight loss with tirzepatide.

Research design and methods: In a secondary analysis of a randomized, double-blind, parallel-arm study, the effects of tirzepatide 15 mg (N = 45), semaglutide 1 mg (N = 44), and placebo (N = 28) on body weight and composition, appetite, and energy intake were assessed at baseline and week 28.

Results: Tirzepatide treatment demonstrated significant reductions in body weight compared with placebo and semaglutide, resulting in greater fat mass reduction. Tirzepatide and semaglutide significantly reduced appetite versus placebo. Appetite scores and energy intake reductions did not differ between tirzepatide and semaglutide.

Conclusions: Differences in energy intake during ad libitum lunch were not sufficient to explain the different weight outcomes. Further evaluation is needed to assess mechanistic differences related to tirzepatide actions on 24-h energy intake, substrate utilization, and energy expenditure.

Trial registration: ClinicalTrials.gov NCT03951753.

Graphical abstract

Figure 1

Change from baseline in body weight and body composition and effect on fat mass reduction on body composition. Data are LSM ± SE of ANCOVA or MMRM on postbaseline or change from baseline values from the pharmacodynamic analysis set. (A) Change from baseline in body weight over time. (B) Change from baseline in body weight at 28 weeks. (C) Change from baseline in fat mass at 28 weeks (percent changes from baseline are in parentheses). (D) Change from baseline in fat-free mass at 28 weeks (percent changes from baseline are in parentheses). (E) Effect of fat mass on body composition (percent of fat or fat-free mass in body mass at 28 weeks are in parentheses). **P < 0.001 versus placebo, ##P < 0.05 and P < 0.001 tirzepatide versus semaglutide 1 mg for MMRM on change from baseline (A and B) and for ANCOVA on change from baseline (C and D). LSM, least squares mean; MMRM, mixed model repeated measures.

Figure 2

Fasting overall VAS score and individual components over time. Data are LSM ± SE of ANOVA on baseline (actual values) and MMRM postbaseline values over time from the pharmacodynamic analysis set. (A) Fasting overall appetite score over time. Note: A higher overall score indicated less appetite. (B) Fasting satiety score over time. Note: A higher overall score indicated less satiety. (C) Fasting fullness score over time. Note: A higher overall score indicated less fullness. (D) Fasting hunger score over time. (E) Fasting prospective food consumption score over time. *P < 0.05 and **P < 0.001 tirzepatide versus placebo; †P < 0.05 semaglutide versus placebo. LSM, least squares mean; MMRM, mixed-model repeated measures.

Figure 3

Energy intake during ad libitum buffet-style lunch. Data are LSM ± SE of ANOVA on baseline and MMRM on postbaseline or change from baseline values from the pharmacodynamic analysis set. (A) Energy intake during ad libitum buffet-style lunch actual values over time. (B) Energy intake during ad libitum buffet-style lunch change from baseline at 28 weeks. *P < 0.05 and **P < 0.001 tirzepatide versus placebo, †P < 0.05 semaglutide versus placebo, and ††P < 0.001 semaglutide versus placebo for MMRM on change from baseline. LSM, least squares mean; MMRM, mixed-model repeated measures.