Comparação de eficácia na perda de peso entre agonistas do receptor de GLP-1 e agonistas duplos GLP-1/GIP: revisão narrativa

Abstract

GLP-1 receptor agonists, such as semaglutide, mimic the action of the hormone GLP-1, produced by the intestine in response to food intake. GLP-1 plays a crucial role in regulating metabolism and maintaining glucose homeostasis, and agonists of this receptor amplify these functions. The main mechanisms of action include increased glucose-dependent insulin secretion, inhibition of glucagon secretion, delayed gastric emptying and reduced appetite. Tirzepatide, a combined GLP-1 and GIP agonist, acts synergistically on two distinct incretin receptors, resulting in amplified glycemic control and weight loss. GIP, also an incretin hormone, stimulates insulin secretion and influences lipid metabolism. Studies have shown that tirzepatide outperformed traditional treatments, with an average 20% reduction in body weight at doses of 10 to 15 mg, while semaglutide, at doses of 2.4 mg, resulted in a reduction of up to 15%. The cardiovascular benefits of GLP-1 agonists are evident in studies such as SUSTAIN-6 and REWIND. This evidence highlights semaglutide as a cardiovascular protective agent, while tirzepatide, due to its dual mechanism, may offer additional metabolic benefits. The safety and tolerability of GLP-1 agonists are fundamental when choosing treatment. Adverse effects such as nausea and gastrointestinal discomfort are common, and the incidence is generally higher at high doses of tirzepatide. Semaglutide, on the other hand, is more tolerable at low initial doses, allowing for gradual titration that minimizes side effects. Direct comparisons show that tirzepatide not only outperforms semaglutide in weight loss, but also in glycemic control, especially in obese populations with type 2 diabetes. However, the high costs of these medications represent significant barriers to their adoption. In the Brazilian context, ensuring their access in the Unified Health System is crucial, not only to treat obesity, but also to reduce costs associated with related diseases, such as cardiovascular diseases.