Fig. 1: Cotadutide improves whole-body and hepatic insulin sensitivity in hyperinsulinemic euglycemic clamp in DIO mice.

Metabolic parameters of DIO mice as assessed via a hyperinsulinemic euglycemic clamp following 28-day treatment of cotadutide (10 nmol/kg, blue upward triangles), liraglutide (5 nmol/kg, purple downward triangles), or g1437 (5 nmol/kg, gold diamonds) compared to vehicle (red circles). Reduction in body weight (BW) throughout the 28-day dosing period is shown as % change (A). Fasting blood glucose prior to clamp (B). Plasma insulin levels during fasting or clamp conditions (C). Blood glucose profile over time during clamp (D). Glucose infusion rate (GIR) (E) and the area under the glucose curve (AUC) (F) over time during the clamp. Rate of glucose disposal during fasting or clamp conditions (G) and plotted against the corresponding plasma insulin levels (H). Hepatic glucose production during fasting or clamp conditions (I) and plotted against the corresponding plasma insulin levels (J). Vehicle (n = 9), cotadutide (n = 8), liraglutide (n = 10), g1437 (n = 8). Data shown as the mean ± SEM. In (A), 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), One-way ANOVA with Tukey’s multiple comparisons post hoc (B, C, F, G, I). *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.