Highlights
The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial has previously established that semaglutide 2.4 mg reduces the risk of major adverse cardiovascular events (MACE) by 20%. This new exploratory analysis expands those findings, focusing on the broader impact on healthcare utilization.
Key findings from the analysis include:
- A 10% reduction in the total number of hospital admissions for any indication (18.3 vs 20.4 per 100 patient-years).
- An 11% reduction in the total number of days spent in the hospital per 100 patient-years.
- A significant decrease in hospitalizations specifically related to serious adverse events (SAEs).
- Consistency in results across various subgroups, including age, sex, and baseline Body Mass Index (BMI).
The Evolving Burden of Obesity and Cardiovascular Disease
Overweight and obesity are well-recognized drivers of cardiovascular disease (CVD), contributing to hypertension, dyslipidemia, and type 2 diabetes. However, even in the absence of diabetes, individuals with obesity and established CVD face a high risk of recurrent events and frequent hospitalizations. Hospitalizations represent a significant burden not only for the patients—impacting quality of life and increasing the risk of hospital-acquired complications—but also for healthcare systems worldwide due to the immense costs associated with inpatient care.
While the primary analysis of the SELECT trial was a landmark study proving that GLP-1 receptor agonists could improve hard cardiovascular outcomes in a non-diabetic population, the impact on the overall healthcare footprint—specifically hospital resource utilization—remained a critical unanswered question. This exploratory analysis addresses that gap, providing a more holistic view of semaglutide’s therapeutic value.
Study Design and Methodology
The SELECT trial was a multicenter, double-blind, randomized, placebo-controlled trial. It enrolled 17,604 patients aged 45 years or older with established CVD (previous myocardial infarction, stroke, or peripheral arterial disease) and a BMI of 27 or higher. Crucially, participants did not have a history of diabetes at enrollment.
Participants were randomized in a 1:1 ratio to receive either once-weekly subcutaneous semaglutide (2.4 mg) or a matching placebo. The median follow-up period was 41.8 months. This prespecified exploratory analysis focused on the total number of hospital admissions and the total duration (days) of hospital stay. To account for multiple admissions per patient, researchers used the Anderson-Gill model and negative binomial regression to calculate mean ratios (MR) and rate ratios (RR).
Key Findings: Reductions in Admissions and Hospital Days
The trial recorded a total of 11,287 hospital admissions during the follow-up period, underlining the high morbidity within this patient population. The results demonstrated a clear benefit for those treated with semaglutide.
Total Hospital Admissions
Patients in the semaglutide group experienced significantly fewer hospitalizations for any indication. The rate was 18.3 admissions per 100 patient-years in the semaglutide group compared to 20.4 in the placebo group. This resulted in a mean ratio (MR) of 0.90 (95% CI, 0.85-0.95; P < .001), representing a 10% reduction in the frequency of admissions.
Hospitalization for Serious Adverse Events
When looking specifically at hospitalizations categorized as serious adverse events, the reduction remained consistent. The semaglutide group had 15.2 admissions per 100 patient-years versus 17.1 in the placebo group (MR, 0.89; 95% CI, 0.84-0.94; P < .001).
Duration of Hospital Stay
Beyond the number of admissions, the total time spent in the hospital was also reduced. The number of days hospitalized for any indication per 100 patient-years was 157.2 for semaglutide versus 176.2 for placebo, a rate ratio (RR) of 0.89 (95% CI, 0.82-0.98; P = .01). Similarly, days hospitalized for SAEs showed an 11% reduction (RR, 0.89; 95% CI, 0.81-0.98; P = .02).
Subgroup Consistency and Clinical Significance
A notable aspect of these findings is their consistency. The reduction in hospital admissions was observed regardless of the patient’s baseline BMI, age, or sex. This suggests that the benefits of semaglutide on healthcare utilization are broadly applicable across the spectrum of patients with obesity and CVD. The lack of heterogeneity in these subgroups reinforces the potential for semaglutide to serve as a foundational therapy in this population.
Expert Commentary: Clinical and Economic Implications
The reduction in hospitalizations is a critical endpoint for clinicians and health policy experts alike. From a clinical perspective, every avoided hospitalization represents a reduction in patient distress and a decreased risk of the ‘post-hospitalization syndrome’—a period of vulnerability where patients are at high risk for readmission and functional decline.
Mechanistically, the reduction in hospitalizations likely stems from a combination of factors. While the reduction in MACE (MI, stroke, CV death) is a primary driver, semaglutide’s effects on weight loss, blood pressure, systemic inflammation, and potentially heart failure symptoms (as seen in the STEP-HFpEF trials) likely contribute to a decrease in non-CV hospitalizations as well. By improving the overall metabolic and cardiovascular health of the patient, semaglutide appears to increase physiological resilience.
From an economic standpoint, these data are vital for cost-effectiveness analyses. Hospitalizations are the most expensive component of cardiovascular care. A 10-11% reduction in hospital bed days could translate into substantial cost savings for healthcare payers, potentially offsetting the acquisition cost of the medication in high-risk populations.
Study Limitations
As an exploratory analysis, these findings should be interpreted with some caution. While the outcomes were prespecified, the trial was not primarily powered to detect differences in total hospital days. Additionally, the specific causes of hospitalization (e.g., cardiovascular vs. non-cardiovascular) were not fully detailed in this specific analysis, which would be helpful for understanding exactly which clinical events are being prevented.
Conclusion
The SELECT exploratory analysis confirms that the benefits of semaglutide 2.4 mg extend far beyond the prevention of major cardiovascular events. By reducing the frequency and duration of hospitalizations, semaglutide offers a meaningful improvement in the clinical course of patients with obesity and established cardiovascular disease. These findings support a paradigm shift in the management of obesity, moving from weight loss alone to a comprehensive strategy for reducing the global burden of disease and healthcare utilization.
Funding and Trial Registration
The SELECT trial was funded by Novo Nordisk. ClinicalTrials.gov Identifier: NCT03574597.
References
1. Nicholls SJ, Ryan DH, Deanfield J, et al. Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease: An Exploratory Analysis of the SELECT Randomized Clinical Trial. JAMA Cardiol. Published online December 23, 2024. doi:10.1001/jamacardio.2025.4824.
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307513.
