Extended Data Fig. 6: Linear regression of maximal plasma glucose concentration during the GTT vs. steady-state GIR prior to the GTT in rats.

For each animal, the maximal plasma glucose concentration during the GTT was plotted against the steady-state GIR prior to the GTT, which represents the quantitative effect of the constant insulin infusion. Nonlinear least squares regression analysis was performed using GraphPad Prism. Slopes for NNC2215, human insulin and human insulin +50% are not statistically significantly different (p = 0.908) as tested using an extra sum-of-squares F test. The slope for the three groups pooled is −0.311 mM/(mg/kg/min). Importantly, the Y-axis intercepts (i.e. the maximal plasma glucose concentration during the GTT) for NNC2215, human insulin and human insulin +50% are statistically significantly different (p < 0.0001), as tested using an extra sum-of-squares F test, with the intercept of the NNC2215 group being in between the human insulin group, which was higher, and the human insulin +50% group, which was lower. Quantitatively, the maximal plasma glucose concentration during the GTT evaluated at GIR = 0 mg/kg/min prior to the GTT was reduced by 18% for NNC2215 vs. human insulin and by 30% for NNC2215 vs. human insulin +50%. Thus, the glucose sensitive effect of NNC2215 was less than the effect of 50% additional human insulin but corresponded more closely to 30% additional human insulin (50% * 18/30). Evaluated at GIR = 15 mg/kg/min prior to the GTT, the effect of NNC2215 during the GTT corresponded to 32% additional human insulin.