Participants with metabolically healthy obesity, compared with at-risk obese subjects, had lower blood levels of glucose, insulin, and C-peptide at baseline and at 30, 60, 90, and 120 min during the 75 g oral glucose tolerance test (OGTT) and lower baseline plasma glucagon levels and appropriate glucagon suppression after oral glucose loading, changes that might be explained by the impaired insulinotropic activity of GIP, despite higher plasma GIP levels and impaired postprandial secretion of GLP-1 in subjects with at-risk obesity. This evidence concerns the gene GIP and obesity due to melanocortin 4 receptor deficiency.