Metabolomics and lipidomics analyses conducted in >250 patients revealed that a 26-week treatment with Tirzepatide significantly modulated a cluster of metabolites and lipids associated with insulin resistance and obesity: 3-hydroxyisobutyrate, branched-chain amino acids, branched-chain ketoacids, and direct catabolic products decreased compared to baseline and placebo [89]; of note, these changes were significantly larger with Tirzepatide than with Dulaglutide, and they were directly proportional to reductions in HbA1c, to indices of insulin resistance, and to proinsulin levels [90]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.