Figure 5.

Metabolic characterization of 6-month-old wildtype and 5XFAD mice treated with semaglutide or tirzepatide. The percentage of body weight change from baseline of regular chow diet-fed 6-month-old female (♀) and male (♂) WT (A, C) and 5XFAD (B, D) mice. Mice were treated with weekly incremental doses of semaglutide (10, 17, 25 nmol/kg), or tirzepatide (2.5, 5, 10 nmol/kg) as indicated in Supplemental Figure 5. (E, F) Glucose excursions following an i.p. glucose challenge in regular chow diet-fed 6-month-old 5XFAD and WT-matched female (E) and male (F) mice treated with semaglutide (25 nmol/kg), tirzepatide (10 nmol/kg), or vehicle (saline). Inset graphs represent the Area Under the Curve (AUC) of the blood glucose excursions. (G–J) Body composition assessed by EchoMRI. Fat mass normalized by body weight of vehicle-, semaglutide (25 nmol/kg)-, or tirzepatide (10 nmol/kg)-treated 5XFAD and WT-matched female (G) and male (H) mice. Lean mass normalized by body weight of vehicle-, semaglutide (25 nmol/kg)-, or tirzepatide (10 nmol/kg)-treated 5XFAD and WT-matched female (I) and male (J) mice. Data were analyzed by 2-way ANOVA with Tukey's post-hoc test for comparison of vehicle vs. treatment. ∗p < 0.05, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 vehicle vs. treatment. Data are represented as means ± SEM (A–D), or as means ± SD (E-J and AUCs). n = 5–10 in each group of vehicle (Veh)-, semaglutide (Sema)-, or tirzepatide (TZP)-treated mice.