We hypothesize that individuals with T2D and a high-obesity cluster PRS might benefit best from weight loss and medical treatments with concomitant weight loss, such as glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose co-transporter 2 (SGLT2) inhibitors; and those with a high PRS for beta-cell dysfunction may display insulin deficiency and may initially try sulfonylureas derivates or need insulin therapy already early on. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.