INS and obesity due to melanocortin 4 receptor deficiency: There were 10 studies belonging to a major clinical trial, the Look AHEAD trial [37–43, 44••, 45, 46] which is a multicentric RCT on adults with T2DM and overweight/obesity (BMI ≥ 25, or BMI ≥ 27 if taking insulin therapy), which compared an intensive lifestyle intervention (ILI) to achieve weight loss through caloric restriction and physical activity, with a Diabetes Support and Education (DSE) group.