Fig. 8.

Drug therapies targeting either peripheral insulin sensitivity (modeled as a rapid increase in S_I) or hepatic insulin sensitivity (modeled as a rapid increase in ${\text{hepa}}_{S_{\text{I}}}$; see Supplemental Tables S13–S16 for details). The drugs are applied in the early stages of type 2 diabetes (A and B) or during prediabetes (C and D). A and C: dominant peripheral insulin resistance, leading to impaired glucose tolerance (IGT)-first pathway as in Fig. 1. B and D: dominant hepatic insulin resistance, leading to impaired fasting glucose (IFG)-first pathway as in Fig. 3. The appropriately targeted drug is more effective than the inappropriately targeted drug in each case, but therapy is more effective when initiated during prediabetes. FPG, fasting plasma glucose; 2hPG, 2 h glucose.