Semaglutide protects the heart beyond weight loss, SELECT study shows

New findings from the landmark SELECT trial reveal that semaglutide's cardiovascular benefits are only partially explained by reduced waist size, suggesting broader protective effects beyond fat loss.

study: Semaglutide and changes in cardiovascular outcomes and adiposity measures by baseline: a prespecified analysis of the SELECT trial. Image credit: Liya Graphics / Shutterstock

In a recent study published in lancetResearchers investigated the association between baseline obesity measurements, treatment-induced changes in obesity, and risk of major adverse cardiovascular events (mace) in Semaglutide Effects of overweight and obese people on cardiovascular disease (choice) Trial.

glucagon– Similar to peptide-1 receptor agonists> GLP-1RAs were originally developed for blood sugar control in type 2 diabetes, and some may be effective in reducing cardiovascular risk and weight in people without diabetes. Obesity is a risk factor for cardiovascular mortality and morbidity, acting through metabolic, inflammatory, and hemodynamic pathways.

Weight alone cannot tell the difference between subcutaneous fat and visceral fat, or distinguish fat-free mass from fat mass. Visceral fat accumulation is thought to be causally related to adverse cardiovascular outcomes. Relationship between baseline obesity, treatment-induced changes in obesity, and subsequent obesity mace is unknown GLP-1RA ordeal.

About research

In this study, researchers investigated the association between baseline obesity measurements, treatment-induced changes in obesity, and changes in obesity. mace risk of choice Trial. choice It was a randomized, placebo-controlled, phase 3 trial evaluating whether semaglutide as an adjunct to standard treatment is superior to placebo in reducing symptoms. mace Risk in 17,604 non-diabetic patients with obesity or overweight and cardiovascular disease (CVD).

Eligible patients are aged 45 years or older and have a body mass index (BMI) ≥ 27 kg/m² CVD (previous stroke, symptomatic peripheral artery disease, or myocardial infarction). Participants were randomly assigned to receive increasing doses of weekly semaglutide or placebo. Participants were randomly assigned to receive 16 weeks of escalating doses of semaglutide or placebo injections. Semaglutide doses were 0.24 mg, 0.5 mg, 1 mg, and 1.7 mg, with target dose (2.4 mg) starting at week 17.

The main results were: macedefined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Changes in waist circumference (toilet) and body weight were estimated from baseline and compared between treatment groups. mace Risk was summarized based on baseline obesity measurements and changes in obesity after randomization.

The analysis of post-randomization changes used an innovative approach that started at week 20 and excluded events before that point, and was observational rather than causal. Association between the first 20 weeks and subsequent changes in obesity mace Risk has been assessed. In addition, mace Risk was analyzed based on change in obesity throughout the study up to death or week 104. Cox proportional hazards models assessed the degree to which changes in obesity were likely to be a marker or mediator of the effect of semaglutide. mace reduction.

Survey results

higher BMI was associated with female gender, younger age, and non-Asian nationality. Prediabetes prevalence, blood pressure, and inflammatory burden showed an increase from lowest to highest BMI Category. The mean duration of exposure was 33.3 and 35.1 months for semaglutide and placebo, respectively, and the mean follow-up was 39.8 months. Decrease in semaglutide mace There is no effect of heterogeneity across baseline physical habit measures.

Within each group, mace Risk was lower in people with lower baseline obesity measurements. In the semaglutide-treated group, the risk decreased by approximately 4% for every 5 kg of baseline weight loss (Human resources department 0.96), but this trend was not significant in the placebo group. For waist circumference, each 5 cm decrease in baseline in both arms was associated with an approximately 4% reduction in risk. toilet. First event by 20 weeks mace Between the arms there were already branches (Human resources department 0.58), supporting early treatment effects.

At the 20th week, you will see an average change in weight and weight. toilet They were -6.4% and -5.0 cm in the semaglutide group, and -0.8% and -1.1 cm in the placebo group, respectively. Obesity changes at week 20 in the semaglutide group accounted for 68% of the weight loss. toilet At week 104, 71% of weight loss was observed. Additionally, there was an overall decrease of 11%. mace Occurred within the first 20 weeks. There was no linear or nonlinear trend in subsequent treatment in the semaglutide group. mace Risk based on weight loss at week 20. However, a linear association between larger values ​​was observed. toilet Decrease and subsequent decline mace risk(Human resources department 0.91, 95% CI 0.84–0.98, p = 0.02). In the placebo group, a nonlinear effect caused by higher factors was observed. mace The incidence of participants with at least 5% weight loss is consistent with the possibility of unintentional weight loss or disease-related weight loss.

Among those who lost weight at week 20, weight was lower in the semaglutide group. mace higher incidence than the placebo group. At week 104, those receiving the placebo who had the greatest weight loss had the highest body weight. mace On the other hand, those receiving semaglutide who lost the most weight had the lowest incidence. The semaglutide group showed a linear trend toward shorter trial duration. mace Risks associated with increased weight loss.

Additionally, the semaglutide group showed a linear trend toward lower values. mace With the change of toilet Notably, there was no evidence that time-varying weight loss mediated the effects of semaglutide. mace. Early accounting toilet Change weakened treatment Human resources department 0.80 to 0.86, indicating partial rather than complete mediation. early toilet Reductions accounted for an estimated 33% of the effect. Among those taking the placebo, those who lost at least 5% of their weight had higher all-cause mortality than the placebo participants who lost less weight or gained less weight.

conclusion

In summary, semaglutide was superior to placebo in reducing symptoms. mace across all baselines toilet or weight level from the beginning of the study. However, early weight loss during the trial was not associated with cardiovascular benefits after 20 weeks. Even further away, toilet was linearly related to the effect of semaglutide. As a result of the mediation analysis, toilet Reductions accounted for 33% of the effect. The post-randomization analysis was exploratory and could not confirm causality, and the authors noted that the majority of the population was white men, which may limit generalizability. These results indicate that the cardioprotective effects of semaglutide extend beyond reducing fat accumulation. Funding: Novo Nordisk. ClinicalTrials.gov NCT03574597.