Pharmacological Therapy in the Obese Patient: Is It Only a Matter of Fat Loss?

Abstract Obesity is a chronic, multifactorial condition strongly associated with increased cardiovascular and metabolic risk, as well as the development of systemic complications. Recent evidence from randomized controlled trials—including SELECT, STEP-HFpEF, STEP-HFpEF DM, SUMMIT, and SURMOUNT-5—has demonstrated the effectiveness of GLP-1 receptor agonists and dual GIP/GLP-1 agonists in the treatment of obesity, with clinical benefits that appear to extend beyond weight reduction alone. In addition to substantial reductions in fat mass, these agents improve cardiovascular parameters (including reductions in major adverse cardiovascular events, MACE), functional capacity, and quality of life. Additional benefits have been observed at the metabolic level, with reductions in glycated hemoglobin, blood pressure, triglycerides, and systemic inflammatory markers such as high-sensitivity C-reactive protein. These results confirm that pharmacological modulation of the incretin axis should not be viewed merely as an adjunctive strategy for weight loss, but rather as an integrated therapeutic intervention capable of modifying overall cardiovascular risk and improving the inflammatory and metabolic profile of the obese patient. In light of these findings, a re-evaluation of the role of pharmacological therapy in the clinical management paradigm of obesity is warranted.