Abstract
OBJECTIVE: To evaluate the efficacy and safety of combining GLP-1 receptor agonists (GLP-1RA) with SGLT-2 inhibitors (SGLT-2i) in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: A comprehensive search of Web of Science, Cochrane Library, Embase, and PubMed was conducted from inception to May 2024. Eligible randomized controlled trials (RCTs) assessing the efficacy of GLP-1RA combined with SGLT-2i for managing T2DM in elderly patients were included. Data extraction and quality evaluation were performed on eligible studies, and meta-analysis was conducted using RevMan 5.3 software. RESULTS: This meta-analysis included 15 studies with a total of 11,679 elderly T2DM patients. The combined GLP-1RA and SGLT-2i therapy significantly improved several clinical outcomes. Hemoglobin A1c (HbA1c) levels were significantly reduced (mean difference [MD] -0.26; 95% confidence interval [CI] -0.32, -0.20; P < 0.0001), indicating effective glycemic control. Renal function, as measured by estimated glomerular filtration rate (eGFR), improved significantly (MD 2.18; 95% CI 1.56, 2.80; P < 0.0001), suggesting renoprotective effects. Lipid profiles also showed improvement, with reductions in LDL cholesterol (MD -0.56; 95% CI -0.64, -0.48; P < 0.0001) and increases in HDL cholesterol (MD 0.18; 95% CI 0.14, 0.22; P < 0.0001). Additionally, systolic blood pressure decreased significantly (MD -3.15 mmHg; 95% CI -4.72, -1.58; P < 0.0001). The combination therapy did not increase the risk of hypoglycemia or other adverse events compared to monotherapy, demonstrating a favorable safety profile. These results support the potential of combined SGLT-2i and GLP-1RA therapy as a comprehensive treatment approach for improving metabolic and cardiovascular health outcomes in elderly T2DM patients. CONCLUSION: Combining GLP-1RA with SGLT-2i provides superior benefits over monotherapy in elderly T2DM patients, particularly for glycemic control, weight management, and cardiovascular protection. This combination also demonstrates a positive safety profile, making it a viable option for clinical use. Ongoing research into the long-term effects and mechanisms of this therapy is necessary to optimize and personalize treatment for elderly patients with type 2 diabetes.