Impact of Frailty
Frailty did not hinder adults with cardiovascular disease and overweight or obesity from experiencing the benefits of semaglutide (Wegovy), according to a secondary analysis of the SELECT trial data.
At week 104, semaglutide’s risk reduction on the primary endpoint—a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke—remained consistent across all frailty levels without detectable heterogeneity (P=0.09 for interaction), reported John Ostrominski, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School in Boston, along with his colleagues.
The results were similar in continuous models when examining frailty, defined as accumulated age-related deficits (P=0.30 for interaction).
Effects on Heart Failure and Mortality
Semaglutide also led to reductions in composite heart failure outcomes (P=0.82 for interaction), all-cause hospitalization (P=0.71 for interaction), and all-cause mortality (P=0.28 for interaction), regardless of frailty category.
Ostrominski remarked, “This is an important message of reassurance. Despite high risks of adverse health outcomes, persons with frailty are often undertreated due to concerns about potentially reduced benefits or increased safety risks. This analysis suggests that the benefit/risk balance may be favorable for semaglutide, even in individuals with frailty.”
Link to Other Therapies
Previous research evaluating GLP-1 drugs for those with frailty has been limited but essential, he noted. The findings align semaglutide with other well-established cardiometabolic therapies, such as SGLT2 inhibitors and finerenone (Kerendia), which have demonstrated reassuring safety and efficacy across frailty categories.
Participants on semaglutide were more likely to see improvements in their frailty categorization (OR 2.46, 95% CI 1.80-3.37) and were less likely to see it worsen (OR 0.47, 95% CI 0.34-0.65), indicating that frailty may be preventable or modifiable, according to Ostrominski.
Ostrominski explained, “Obesity is a significant risk factor for dysfunction across multiple organ systems and consequently is associated with premature disability and frailty. While further research is certainly necessary, these findings suggest that optimal management of obesity may improve markers of frailty over time.”
Quality of Life Improvements
While many main findings were somewhat anticipated, Ostrominski highlighted a key takeaway: frailer participants experienced greater improvements in health-related quality of life as measured by EuroQol 5-Dimension 5-Level index scores (P=0.02 for interaction) compared to their non-frail counterparts, primarily driven by enhancements in mobility, self-care, and usual activities.
They were also less likely to discontinue semaglutide due to adverse events when compared with those in the placebo group (P<0.001 for interaction).
Individualized Treatment Decisions
Ultimately, decisions regarding the use of GLP-1-based therapies should always be personalized and made in consultation with a healthcare professional, regardless of frailty status, Ostrominski emphasized. “I would recommend focusing on optimal dietary and physical activity strategies for individuals treated with GLP-1 therapies,” he advised.
The post-hoc analysis of the SELECT trial included 17,604 adults with a body mass index of 27 or higher and established cardiovascular disease without diabetes. The average age was 61.6 years, and 72.3% were male.
Frailty was measured using a 31-item scale and stratified participants into three groups: not frail (frailty index [FI] score ≤0.210; 31% of cohort), more frail (FI 0.211-0.310; 47%), and most frail (FI ≥0.311; 22%). Frailer participants exhibited higher body mass index, additional obesity-related complications, and poorer health-related quality of life. They were also more likely to be older, female, and current or former tobacco users.
Limitations of the Study
Ostrominski pointed out two primary limitations. “First, this was a secondary analysis of a clinical trial, so these findings should be interpreted cautiously,” he explained.
“Second, this analysis defined frailty using a frailty index that captures the total burden of age-related deficits. While this is a well-validated method, alternative frailty definitions exist, like physical frailty phenotypes based on weakness and slow gait speed, among other factors,” Ostrominski added.
The authors noted that despite the large trial size, exploratory frailty subgroups might have been underpowered, making these findings more of a hypothesis-generating nature.
“Further studies on GLP-1 receptor agonists are necessary, especially in groups with low muscle mass or low muscle function,” concluded Ostrominski.
Disclaimer: This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for personalized advice and treatment options.
Fuente: https://www.medpagetoday.com/cardiology/prevention/123063
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