META-ANALYSIS OF CARDIOPROTECTIVE EFFECTS OF COMBINED SGLT2 INHIBITORS AND GLP-1 RECEPTOR AGONISTS VS. MONOTHERAPY IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE: IMPACT ON MORTALITY AND HOSPITALIZATION OUTCOMES

Abstract

Background: Type 2 diabetes mellitus (T2DM) combined with heart failure (HF) markedly raises cardiovascular risk, underscoring the need for integrated therapeutic strategies. Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in managing glycemic control and enhancing cardiovascular outcomes. While both therapies independently offer cardioprotective effects, combining SGLT2 inhibitors and GLP-1 receptor agonists may provide superior efficacy in reducing mortality and hospitalizations in this vulnerable population.

Objective: To assess the cardioprotective efficacy of combined SGLT2 inhibitors and GLP-1 receptor agonists versus monotherapy on cardiovascular outcomes, specifically mortality and hospitalization rates, in patients with T2DM and HF.

Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar following PRISMA guidelines. Studies included were randomized controlled trials (RCTs) and observational studies that evaluated the impact of SGLT2 inhibitors, GLP-1 receptor agonists, or their combination on cardiovascular outcomes, specifically mortality and hospitalization rates, in patients with T2DM and HF. A random-effects model was applied to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs), adjusting for heterogeneity.

Results: Analysis included 10 studies encompassing T2DM and HF patients, with combined therapy showing superior efficacy. The pooled RR indicated a significant reduction in mortality (RR: 0.78; 95% CI: 0.70–0.88; p < 0.001) and hospitalizations (RR: 0.85; 95% CI: 0.77–0.93; p = 0.002) with combination therapy compared to monotherapy. However, a slight increase in gastrointestinal side effects was observed (RR: 1.10; 95% CI: 1.02–1.20; p < 0.05).

Conclusion: Combined therapy with SGLT2 inhibitors and GLP-1 receptor agonists is potentially more effective than monotherapy for cardiovascular risk reduction in T2DM patients with HF, despite a marginal increase in gastrointestinal side effects. This supports the clinical consideration of combination therapy to optimize cardiovascular outcomes in this high-risk group.