Effect of new classes of antidiabetic drugs on cardiovascular outcomes in randomised controlled trials: a network meta-analysis

[Speaker] Yue Fei:1
[Co-author] Man-Fung Tsoi:1, Cyrus R Kumana:1, Tommy Tsang Cheung:1, Bernard Man Yung Cheung:1
1:Department of Medicine, The University of Hong Kong, Hong Kong

Background: The prevalence of cardiovascular disease is high in patients with type 2 diabetes mellitus (T2DM). New antidiabetic drugs are required to demonstrate safety in cardiovascular outcome trials. However, they are rarely compared with each other. Therefore, we performed a network meta-analysis to compare the effect of new classes of antidiabetic drugs on cardiovascular outcomes.
Methods: We searched for cardiovascular outcome trials 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 T2DM patients with major adverse cardiovascular events (MACE) and mortality as endpoints. Data were analysed using both frequentist approach and Bayesian framework in R.
Results: Nine cardiovascular outcome trials with altogether 72262 T2DM patients were eligible to be included. Compared to placebo, GLP-1 RAs and SGLT-2 inhibitors reduced MACE (OR 0.89, 95% CI 0.82-0.97 and 0.86, 0.77-0.95), all-cause mortality (0.89, 0.80-0.99 and 0.78, 0.69-0.88), and cardiovascular mortality (0.85, 0.73-0.99 and 0.76, 0.65-0.88), respectively. Moreover, SGLT-2 inhibitors lowered the risk of MACE and cardiovascular death (0.87, 0.77-0.98 and 0.75, 0.62-0.90, respectively) when compared to DPP-4 inhibitors. In contrast, DPP-4 inhibitors, although, were not significantly different from placebo in cardiovascular outcomes, they were associated with higher all-cause mortality when compared to GLP-1 RAs (1.16, 1.01-1.33) and SGLT-2 inhibitors (1.31, 1.13-1.53).
Conclusions: GLP-1 RAs and SGLT-2 inhibitors reduce MACE and mortality compared to placebo. DPP-4 inhibitors do not worsen cardiovascular outcomes but are inferior to SGLT-2 inhibitors and GLP-1 RAs. SGLT-2 inhibitors are the most beneficial in protecting against cardiovascular events among the three drug classes. This network meta-analysis supports SGLT-2 inhibitors and GLP-1 RAs as the preferred treatment for T2DM patients.
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