In a cohort of adults with overweight/obesity (mean BMI ≈ 37 kg/m2) managed in real-world clinical practice, the Adaptive Ketogenic–Mediterranean Protocol (AKMP)—which combines nutritional ketosis within a Mediterranean matrix and an anti-plateau algorithm—achieved its primary endpoint over ≈ 14 weeks, with substantial improvement in the glucose–insulin axis (ΔHOMA-IR −52.8%; p < 0.001). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.