IMR of female mice produces similar beneficial plasma hormone and glycemic changes to continuous MR. Longitudinal comparisons of the plasma concentrations of (a) IGF‐1, (b) leptin, (c) adiponectin, (d) FGF‐21, as well as the blood concentrations of (e) glucose, and (f) insulin for female mice that were control‐fed (CF), continuously methionine‐restricted (MR), subjected to stringent IMR (IMR2), or fed similarly to IMR2 animals but provided methionine in their drinking water (IMR2 + MET). Colored triangles denote that sampling of the indicated groups occurred following a period of MR. Metabolic tolerance tests (glucose, GTT; insulin, ITT) were performed for female mice that were either control‐fed or subjected to stringent IMR (g‐h), as well as area‐under‐the‐curve (AUC) analyses of the resulting data (i‐j), and determination of blood concentrations of β‐hydroxybutyrate for animals subjected to control or IMR feeding (k). For all panels, bars denote SEM. Statistically significant differences (as compared with CF values) are indicated (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001). For panels a‐f, statistically significant differences between MR and IMR2 values are either indicated (**p < 0.01; ***p < 0.001; ****p < 0.0001) or absent (ns). For panels A‐F, N = 8 for all groups; for panels g‐k, N = 6 for all groups