This research is Trending!
September 17, 2026JAMA Cardiology
Efficacy and Safety of Semaglutide According to Frailty Status
Why the study?
Does semaglutide 2.4 mg once weekly reduce cardiovascular events in adults with cardiovascular disease and overweight/obesity regardless of frailty status?
Population
17,604 adults with a body mass index of 27 or higher and established cardiovascular disease without…
Comparison
Semaglutide 2.4 mg once weekly vs Placebo
Design
RCT
Follow-up
104 weeks
Key result
Semaglutide consistently reduced cardiovascular death, nonfatal MI, and nonfatal stroke across frailty categories (HRs 0.70 to 0.92; P=0.09 for interaction) without detectable heterogeneity.
Authors
Discussion
Loading...
Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
MCMedscape Cardiology
“What was less expected was that persons with frailty appeared to derive greater benefits on how they felt and functioned (eg, mobility appeared to improve more with semaglutide in persons with frailty); and that, compared with placebo, persons with greater frailty were actually less likely to dis...”
“There are persistent concerns around the balance of risk and benefit with GLP-1 receptor agonist–based medications, such as semaglutide, in this population. As a result, some healthcare providers are hesitant to prescribe GLP-1s for older adults.”
KGKelley GregorovicRN, nurse practitioner
“Frailty is something we absolutely need to consider when we're treating older adults. But I don't want frailty alone to become a reason that patients can't access these medications, particularly when we know the benefits can extend well beyond weight loss.”
Overview
Supports semaglutide use across frailty levels in CVD; extends SELECT benefits to frail subgroups without heterogeneity.
Key Points
- To determine whether baseline frailty status modifies the clinical efficacy and safety of semaglutide in adults with cardiovascular disease and overweight or obesity without diabetes.
- Secondary analysis of the SELECT randomized clinical trial (NCT03574597) evaluating 17,604 adults with BMI ≥27 and established cardiovascular disease assigned to once-weekly semaglutide 2.4 mg or placebo.
- Frailty was assessed using a 31-item cumulative deficit frailty index (FI) categorizing participants as not frail (FI ≤0.210; n=5,432), more frail (FI 0.211–0.310; n=8,349), or most frail (FI ≥0.311; n=3,823).
- Semaglutide reduced the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke consistently across frailty categories: FI ≤0.210 (HR 0.84, 95% CI 0.65–1.07), FI 0.211–0.310 (HR 0.70, 95% CI 0.59–0.82), and FI ≥0.311 (HR 0.92, 95% CI 0.76–1.10; P = .09 for interaction; continuous FI interaction P = .30).
- Reductions in heart failure outcomes (interaction P = .82), all-cause hospitalization (interaction P = .71), and all-cause mortality (interaction P = .28) were consistent across all frailty strata.
- Semaglutide was associated with greater improvements in EQ-5D-5L quality-of-life scores in higher FI groups (interaction P = .02), increased odds of FI category improvement by week 104 (OR 2.46, 95% CI 1.80–3.37), and decreased odds of worsening frailty (OR 0.47, 95% CI 0.34–0.65).
Study Design
Type
RCT (n=17,604)
Randomization
randomized
Structured PICO
Does semaglutide 2.4 mg once weekly reduce cardiovascular events in adults with cardiovascular disease and overweight/obesity regardless of frailty status?
P
Population
17,604 adults with established cardiovascular disease, overweight/obesity, and no diabetes, evaluated by baseline frailty index.
I
Intervention
Semaglutide 2.4 mg once weekly
C
Comparator
Placebo
O
Outcome
Composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal strokecomposite
Semaglutide 2.4 mg once weekly provides consistent cardiovascular benefits and improves quality of life across varying levels of frailty in patients with established cardiovascular disease and overweight or obesity.
Trending Research#3 this week
Immediate media coverage (Healio); aligns with ongoing GLP-1 discussions; high downloads likely; frailty is hot topic in cardiology.
Social attention
75
Preprint velocity
30
News coverage
85
Conference
60
Expert commentary
70
Cite This Study
Ostrominski et al. (2026) conducted an RCT in cardiovascular disease and overweight/obesity (n=17,604). Semaglutide vs. placebo was evaluated on cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Semaglutide consistently reduced cardiovascular death, nonfatal MI, and nonfatal stroke across frailty categories (HRs 0.70 to 0.92; P=0.09 for interaction) without detectable heterogeneity.