Obesity update: cardiovascular risk and therapeutic innovations (focus on semaglutide and tirzepatide)

Excess or dysfunctional adipose tissue is a key pathophysiological factor in cardiovascular-kidney-metabolic syndrome. However, until very recently, there was no evidence that pharmacological treatments for obesity could significantly impact major cardiovascular outcomes. Recently, the SELECT study represented the first, and to date the only, cardiovascular outcome trial conducted in the context of pharmacological treatment for obesity, and subcutaneous (s.c.) semaglutide 2.4 mg is the first molecule capable of leading to a statistically significant reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in obese, non-diabetic patients with pre-existing cardiovascular disease. Furthermore, in the context of heart failure with preserved ejection fraction with obesity-related phenotype, s.c. semaglutide 2.4 mg and tirzepatide have been shown to improve prognosis, functional capacity, and quality of life. The main limiting factors for the implementation of semaglutide and tirzepatide are represented by the suboptimal adherence to treatment due to gastrointestinal intolerance, as well as by the reduced accessibility and economic sustainability. It is therefore necessary to wait to see how the drug regulatory agencies and international guidelines will implement the evidence of semaglutide and tirzepatide in the specific setting of the cardiovascular risk of obese patients.