What is the correct statement about the use of Glucagon-like peptide-1 (GLP-1) agonists in older adults compared to the general adult population regarding major adverse cardiovascular events (MACE) and adverse event rates?

GLP-1 Agonists in Older Adults: Efficacy and Safety Profile

GLP-1 agonists are associated with similar or greater reductions in major adverse cardiovascular events (MACE) and lower adverse event rates in older adults compared to the general adult population.

Cardiovascular Benefits in Older Adults

GLP-1 receptor agonists demonstrate significant cardiovascular benefits in older adults that are at least comparable to, and sometimes greater than, those observed in younger populations:

• Stratified analyses of cardiovascular outcome trials indicate that older adults experience similar or greater benefits from GLP-1 agonists than younger people 1
• In patients ≥65 years, GLP-1 agonists reduce MACE (hazard ratio 0.86; 95% CI 0.80-0.92), cardiovascular death, stroke, and myocardial infarction 2
• Similar benefits were observed in patients ≥75 years, indicating consistent efficacy across older age groups 2
• When compared to DPP-4 inhibitors in Medicare beneficiaries, GLP-1 agonists showed significant cardiovascular benefits with a hazard ratio of 0.74 (95% CI 0.71-0.77) 3

Safety Profile in Older Adults

GLP-1 receptor agonists demonstrate a favorable safety profile in older adults:

• Severe adverse events were not more frequent with GLP-1 agonists than with DPP-4 inhibitors in older adults 3
• GLP-1 agonists are associated with lower rates of hypoglycemia compared to insulin or sulfonylureas, which is particularly important for older adults 1
• While GLP-1 receptor agonists may cause gastrointestinal side effects (nausea, vomiting, diarrhea), these typically do not result in discontinuation of the drug 4

Considerations for Frail Older Adults

The benefits of GLP-1 agonists appear to be even more pronounced in frail older adults:

• In a large Medicare study, the absolute cardiovascular benefit of GLP-1 agonists was greater in frail older adults compared to non-frail older adults 3
• The incidence rate difference for cardiovascular outcomes was -7.02 in the lowest frailty stratum but -25.88 in the highest frailty stratum (p for interaction <0.01) 3

Potential Limitations and Cautions

Despite their benefits, certain considerations should be kept in mind when prescribing GLP-1 agonists to older adults:

• Injectable GLP-1 receptor agonists require adequate visual, motor, and cognitive skills that may be compromised in very elderly patients 5
• GLP-1 receptor agonists may be associated with nausea, vomiting, and diarrhea, which could be problematic for older adults experiencing unexplained weight loss 1
• Benefits may not be clinically significant in patients with life expectancy less than 4 years 6
• Potential harm from injectable GLP-1 agonists may occur in the oldest categories of adults with type 2 diabetes due to injection-related disutility 6

Clinical Application

When considering GLP-1 agonists for older adults:

1. Assess cardiovascular risk - these agents are particularly beneficial for older adults with established ASCVD or high cardiovascular risk
2. Evaluate functional status - ensure the patient has adequate visual, motor, and cognitive skills if using injectable formulations
3. Consider weight status - be cautious in older adults with unexplained weight loss
4. Assess life expectancy - benefits may be limited in those with very short life expectancy (<4 years)
5. Monitor for adverse effects - particularly gastrointestinal symptoms which may be more problematic in older adults

In conclusion, the evidence strongly supports that GLP-1 agonists provide similar or greater cardiovascular benefits in older adults compared to younger populations, while maintaining a favorable safety profile with lower adverse event rates.