INS and obesity due to melanocortin 4 receptor deficiency: The existing studies have been summarized in one systematic review and five meta-analyses [6, 7, 18–21], and these syntheses suggest a possible improvement in insulin sensitivity, but a major challenge in interpreting these results is that they did not account for the heterogeneity of patients in terms of baseline body mass index (BMI), T2D status, and prior obesity (bariatric) surgery.