BACKGROUND: Type 2 diabetes mellitus is highly prevalent among older adults and often requires multidrug therapy to optimize glycemic control while minimizing adverse effects. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective antihyperglycemic drugs with demonstrated cardiometabolic benefits. However, their real-world safety, tolerability, and long-term outcomes in geriatric populations remain under-explored.
OBJECTIVE: To qualitatively analyze completed Phase 4 interventional trials evaluating GLP-1 RA therapy among older adults (≥65 years) with diabetes, as registered on ClinicalTrials.gov.
METHODS: A descriptive qualitative review was performed using data from all completed Phase 4 interventional studies with posted results involving older adults and GLP-1 RA therapy for diabetes. Trials were identified through a structured search of ClinicalTrials.gov up to 10 November 2025. Extracted data included drug name, comparator type, outcome measures, and enrollment size. Descriptive qualitative analyses were conducted to summarize treatment trends and reported safety outcomes.
RESULTS: Thirty-seven Phase 4 studies met inclusion criteria. Liraglutide (n = 12) and semaglutide (n = 8) were most frequently investigated, followed by dulaglutide (n = 7), exenatide (n = 5), and lixisenatide (n = 3). Across trials (median enrollment = 180, range = 23-1100), primary endpoints focused on glycated hemoglobin (HbA1c) reduction (45.9%), cardiovascular risk markers (27%), and safety (18.9%). Most studies demonstrated significant improvements in glycemic control and body weight, with frequent adverse effects of gastrointestinal intolerance (15-30%), injection-site reactions (≤5%), and low rates of hypoglycemia (<5%).
CONCLUSION: This qualitative synthesis highlights consistent clinical benefits of GLP-1 RAs in older adults with diabetes, though tolerability and adherence remain concerns. Post-marketing data underscore the need for individualized prescribing and further research on long-term safety, renal outcomes, and polypharmacy interactions in geriatric populations.
