CONGRESS ABSTRACT

Background. SGLT2-i (sodium-glucose cotrasporter-2 inhibitor) and GLP1-RA (glucagon-like peptide receptor agonist) are two new classes of glucose-lowering drugs for the treatment of diabetes mellitus. Several important randomized clinical trials demonstrated a reduction in the risk of cardiovascular events in patients with type 2 diabetes mellitus treated with SGLT2-i and GLP1-RA. The aim of this work is to carry out a systematic review and meta-analysis that evaluates cardiovascular outcomes in terms of MACE (Major Adverse Cardiovascular Events) in diabetic patients treated with SGLT2-i vs placebo and GLP1-RA vs placebo. A indirect comparison, SGLT2-i vs GLP1-RA, will be made between the two estimates obtained. Methods. This meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A systematic search was carried out from 1 January 2008 to 31 July 2024 using Medline, Web Of Science, Scopus. We selected multinational randomized controlled clinical trials reporting cardiovascular outcomes in terms of MACE including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RoB 2). The absolute and relative risk reduction (ARR and RRR) of MACE events were calculated with a 95% confidence interval by the Mantel-Haenszel method. The statistical model with random effects was applied to combine the effect sizes of the studies assuming heterogeneity between them. Results. 12 clinical trials were selected; 4 compare SGLT2-i versus placebo and 8 GLP1-RA versus placebo. Applying the random-effect model we obtain: an RR for MACE of 0.87 (95% CI:[0.82,0.93]) and an RRR of 13% with GLP1-RA; an RR for MACE of 0.91 (95% CI:[0.84,0.99]) and an RRR of 9% with SGLT2-i. The absolute risk reduction (ARR) is -0.01 (95% CI:[-0.02,-0.01]) with GLP1-RA and -0.01 (95% CI:[-0.02,-0.00]) with SGLT2-i. To compare the two RRs for MACE obtained, an "indirect comparison" returned rRR=1.05 (95% CI:[0.94,1.16]) and a p=0.39. Conclusions. SGLT2-i and GLP1-RA therapy shows, compared to placebo, a comparable and significant efficacy in reducing the MACE composite outcome. These results suggest to support the clinical use of these drugs in the management of diabetic patients.