The Impact of Oral Hypoglycemic Agents on Elderly Patients: A Meta-analysis (2000–2025)

This meta-analysis evaluated the effectiveness and safety of oral hypoglycemic agents (OHAs) in elderly patients (≥65 years) with type 2 diabetes mellitus, synthesizing evidence from 98 studies (56 randomized controlled trials, 42 cohort/meta-analyses) comprising over 67,400 participants published between 2000 and 2025. Primary outcomes included glycemic control, hypoglycemia incidence, weight changes, cardiovascular and renal effects, and adverse events. All major OHA classes significantly reduced HbA1c compared to baseline or placebo, with mean reductions ranging from 0.72% (DPP-4 inhibitors) to 1.05% (metformin). Combination therapies enhanced glycemic efficacy without significantly increasing adverse events. Sulfonylureas displayed a higher risk of severe hypoglycemia, especially in frail patients or those with renal insufficiency, while metformin remained weight-neutral and sodium-glucose cotransporter 2 (SGLT2) inhibitors promoted weight loss. Cardiovascular outcomes favored SGLT2 inhibitors and GLP-1 receptor agonists, reflected in reduced cardiovascular events and slower renal decline. Adverse event rates were overall comparable across regimens, though SGLT2 inhibitors increased urinary/genital infection risk. The study highlights the importance of individualized therapy, emphasizing metformin, SGLT2 inhibitors, and DPP-4 inhibitors for optimal balance of efficacy and safety, while recommending judicious use of sulfonylureas and careful consideration of patient comorbidities and preferences to maximize outcomes.