B. M. Y. Cheung1, Y. Fei1, M. F. Tsoi1 (1Hong Kong HK)
Aim: New antidiabetic drugs are required to be evaluated in cardiovascular outcome trials (CVOTs). Few of these are direct comparisons between new drugs, so we performed a network meta-analysis to compare the new drug classes in terms of cardiovascular outcomes.
Method: We searched for CVOTs involving glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes using major adverse cardiovascular events (MACE) and mortality as endpoints. Network meta-analysis was performed using random-effects model in R.
Results: 13 CVOTs with altogether 116746 patients were included (fig. 1). GLP-1 RAs and SGLT-2 inhibitors significantly lowered the risk of MACE (OR 0.87, 95% CI 0.82-0.94 and 0.89, 0.82-0.97), all-cause mortality (0.90, 0.82-0.99 and 0.84, 0.76-0.93), heart failure (0.87, 0.82-0.93 and 0.70, 0.62-0.80), and renal composite outcome (0.85, 0.75-0.97 and 0.63, 0.55-0.72) when compared to placebo (fig. 2). GLP-1 RAs reduced nonfatal stroke (0.88, 0.77-0.99) while SGLT-2 inhibitors reduced cardiovascular mortality (0.83, 0.72-0.96). In contrast, DPP-4 inhibitors did not significantly alter the risk of these outcomes.
Conclusion: GLP-1 RAs and SGLT-2 inhibitors both reduce MACE, heart failure, renal composite outcome, and all-cause mortality when compared to placebo. DPP-4 inhibitors did not show any cardiovascular benefits. Our findings support using SGLT-2 inhibitors and GLP-1 RAs for diabetic patients with high cardiovascular risk.