GLP-1RAs, including semaglutide, show promise for cardiometabolic risk reduction in aging people with HIV
Background
People with HIV (PWH) face a disproportionately high burden of cardiometabolic disease and aging-related comorbidities, often exacerbated by chronic inflammation and antiretroviral therapy side effects. Traditional interventions for type 2 diabetes and obesity may not fully address the complex needs of this population, leaving a significant treatment gap. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for metabolic conditions, are now being investigated for their potential to mitigate these risks in PWH, given their pleiotropic effects on glucose homeostasis, weight, and inflammation.
Study Design
This review synthesized emerging evidence on the efficacy, safety, and implementation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in People with HIV (PWH), particularly focusing on the aging population. The authors systematically summarized findings from studies investigating GLP-1RAs, such as semaglutide, across various cardiometabolic and behavioral outcomes. The review also considered specific challenges and clinical implications for aging and multimorbid PWH, evaluating existing data on body composition, tolerability, and functional outcomes to provide a comprehensive overview.
Results
GLP-1RAs, including semaglutide, are associated with meaningful reductions in bodyweight, glycemia, and both visceral and hepatic fat in PWH. Emerging data suggest potential effects on behavioral outcomes such as alcohol use and smoking, although evidence in PWH remains limited. Concerns regarding lean mass loss, frailty, and bone health exist, but current data are generally reassuring, with functional outcomes largely preserved across studies. Most HIV-specific studies have largely used lower doses of semaglutide, and evidence specifically in older populations remains sparse. The review highlights GLP-1RAs as a promising option for cardiometabolic risk reduction in PWH. Future research is prioritized for assessing cardiovascular, neuropsychiatric, and substance use outcomes.
GLP-1RAs, including semaglutide, are linked to significant reductions in bodyweight, glycemia, and both visceral and hepatic fat in PWH.
Key Findings
- GLP-1RAs reduce bodyweight, glycemia, visceral, and hepatic fat in people with HIV.
- GLP-1RAs show potential for impacting alcohol use and smoking in people with HIV.
- Concerns about lean mass loss, frailty, and bone health with GLP-1RAs are generally reassuring.
- Most HIV-specific studies used lower doses of semaglutide.
- Evidence for GLP-1RAs in older people with HIV populations is sparse.
Why It Matters
GLP-1RAs represent a significant new tool for managing cardiometabolic risk in PWH, a population with a high comorbidity burden and unique treatment considerations. Clinicians should consider GLP-1RAs, particularly semaglutide, for PWH struggling with obesity and type 2 diabetes, while carefully monitoring body composition and tolerability. This review suggests that while promising, a cautious approach is warranted, especially regarding potential lean mass loss in vulnerable aging populations. Future protocols may integrate GLP-1RAs more broadly, but further research is needed to optimize dosing, understand long-term effects on frailty and bone health, and explore behavioral benefits, moving towards personalized treatment strategies.
glp-1ra
semaglutide
hiv
cardiometabolic-disease
obesity
type-2-diabetes