Fig. 2: Cotadutide-treated DIO mice have normal insulin secretory capacity in response to hyperglycemia.

Metabolic parameters of DIO mice as assessed via a hyperglycemic clamp following 7-day treatment of cotadutide (10 nmol/kg, blue upward triangles), liraglutide (10 nmol/kg, purple downward triangles), or g1437 (10 nmol/kg, gold diamonds) compared to vehicle (red circles). Reduction in body weight (BW) throughout the 7-day dosing period is shown as % change (A). Fasting blood glucose (B) and fasting plasma insulin (C) prior to the clamp. Glucose infusion rate (GIR) (D), blood glucose levels (E), the area under the glucose curve (AUC) (F), and plasma insulin levels (G) during clamp conditions. Glucose disposal (Rd) under fasting and clamp conditions (H). Endogenous glucose production under fasting and clamp (I). Baseline (core) glycogen levels prior to clamp (J), net glycogen synthesis during clamp (K), and total glycogen at the end of the clamp (L). Vehicle (n = 10), cotadutide (n = 9), liraglutide (n = 9), g1437 (n = 10). Data are shown as the mean ± SEM. In (A, D, G), lines above the graph indicate differences compared with the vehicle at each time point and correspond to the respective group color. Two-way ANOVA with Tukey’s multiple comparisons post hoc (A, D, G), One-way ANOVA with Tukey’s multiple comparisons post hoc (B, C, F, H–L). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < .0001. Exact p values are included in the Source Data file. Source data are provided as a Source Data file.