GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
weight loss achieved through lifestyle changes | decrease | risk factors | - | - | lowers | #1 |
weight loss achieved through lifestyle changes | no change | cardiovascular outcomes | - | - | has no clear effect | #2 |
treating obesity with GLP-1RA | decrease | cardiovascular risk | - | - | decreases | #3 |
GLP-1RA | decrease | glycemia | type 2 diabetes patients | - | effects upon | #4 |
long-acting GLP-1RA | decrease | weight | type 2 diabetes patients | - | weight loss | #5 |
GLP-1 receptor agonists | decrease | cardiovascular risk | type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight | - | were indeed capable of decreasing | #6 |
GLP-1RA liraglutide and semaglutide | neutral | a ground-breaking therapy specific for obesity | - | - | paved way to | #7 |
SCALE 3 mg/day liraglutide program | neutral | therapy specific for obesity | - | - | shown with | #8 |
STEP 2.4 mg/week semaglutide program | neutral | therapy specific for obesity | - | - | shown with | #9 |
tirzepatide | neutral | - | - | - | a novel molecule with superior performance | #10 |
GLP-1RA to treat obesity | neutral | clinical science | - | - | have become a hallmark | #11 |
GLP-1RA to treat obesity | neutral | cardioprotective effects | - | - | concomitant | #12 |
PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.