It is well known that the efficacy of insulin therapy is counterbalanced by the risk of hypoglycemia and undesired weight gain, and our study clearly documents that, in subjects with T2D who intensified hypoglycemic therapy with insulin therapy over three 5 years (2005–2019), the average BMI value remained high (overweight) and almost unchanged over time. The gene discussed is INS; the disease is type 2 diabetes mellitus.