Cardiometabolic impact of new drugs

Abstract

Obesity is a key condition, the basis of metabolic, cardiovascular and kidney diseases, and a main participant in the pathophysiology of type 2 diabetes mellitus (DM2) and its complications. Metabolic alterations leading to hyperglycemia are usually present decades before the diagnosis of T2DM, and are characterized by weight gain, central adiposity, and insulin resistance.

There is evidence that loss of 5% to 10% of total body weight is associated with a reduction in the risk of metabolic and mechanical complications. However, the impact on cardiovascular complications is observed with a reduction of more than 15%¹. The incorporation of new molecules, such as long-acting agonists of the glucagon-like peptide 1 (AR-GLP1) receptor and co-agonists of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, established a significant change in the treatment of obesity, DM and related complications¹. At the cardiovascular level, the GLP1-RAs liraglutide 1.8 mg (LEADER) and semaglutide 1 mg (SUSTAIN-6) demonstrated a reduction in the rate of death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke (MACE) in people with DM2^2-4.

In relation to the progression of renal failure in people with DM2 and CKD, the results of the FLOW study demonstrate a 24% reduction in the group treated with semaglutide 1 mg in the result composed of renal and cardiovascular endpoints2-4. In people with obesity and established cardiovascular disease without T2DM, semaglutide 2.4 mg demonstrated a 20% reduction in MACE (SELECT) and was shown to be a useful option for the treatment of heart failure (HF) with preserved ventricular ejection fraction left (LVEF) in people with obesity and T2DM (STEP HFpEF DM) and without T2DM (STEP HFpEF), reducing physical limitations and symptoms related to HF. Regarding tirzepatide, a GLP 1 and GIP receptor coagonist, the evaluation of the safety of this drug in T2DM and established atherosclerotic disease is under development in the SURPASS-CVOT2-4 trial. The future came with new molecules for the treatment of obesity and T2DM and, as a result, a reduction in cardiorenal and hepatic complications, and an excellent opportunity for pharmacological intervention.