Background Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors, Glucagon-Like Peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 (DPP-4) inhibitors are the three latest drug classes to receive regulatory approval for the treatment of type 2 diabetes. Although pharmacological treatment with these agents improves glycaemic control, macrovascular complications of type 2 diabetes remains a considerable clinical challenge. While there have been several cardiovascular outcome trials using these drug classes, there have been no head-to-head clinical outcome trials and their comparative efficacies for cardiovascular endpoints remains unknown. The aim of this study is to investigate the comparative efficacy of SGLT-2 inhibitors, GLP-1 agonists and DPP-4 inhibitors for acute coronary syndrome.
Methods MEDLINE, Embase, CENTRAL and published meta-analyses through October 11, 2017 were searched. Randomised controlled trials included for meta-analysis were required to enrol participants with type 2 diabetes and a follow-up of at least 12 weeks, where SGLT-2 inhibitors, GLP-1 agonists and DPP-4 inhibitors were compared with either each other, placebo or unblinded control.Outcomes were myocardial infarction (any and non-fatal events), and unstable angina. Random-effects frequentist network meta-analysis was used for indirect comparisons. P-score statistic was used to determine probability of individual drug type being best in class.
Results There were 108 comparisons totalling 1 27 731 participants (figure 1). Only SGLT-2 inhibitors reduced all MI when compared with control (RR 0.86, 95% CI 0.75 to 0.99, p=0.032) (figure 2). There were no effects with GLP-1 agonists (RR 0.95, 95% CI 0.88 to 1.03, p=0.19) or DPP-4 inhibitors (RR 0.93, 95% CI 0.84 to 1.04, p=0.22) compared with control. There was no difference between drug classes. Similar results were seen for non-fatal MI. No drug class had any effect on unstable angina. SGLT-2 inhibitors were most likely to rank highest for efficacy for all outcomes (figure 2).
Conclusion When compared with control treatment, SGLT-2 inhibitors were the only drug class to reduce myocardial infarction and were most likely to be the most efficacious. There have been no head-to-head cardiovascular outcome-driven RCTs comparing SGLT-2 inhibitors with incretin-based therapies. Without any such trials on the horizon, network-meta analysis is the only Method to provide comparative estimates between these agents. This study supports the use of SGLT-2 inhibitors for the reduction of acute coronary syndrome events in patients with type 2 diabetes.
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