Yue Fei1, Man-Fung Tsoi1, Cyrus Rustam Kumana1, Tommy Tsang Cheung1, Bernard Man Yung Cheung2. 1. Division of Clinical Pharmacology and Therapeutics, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. 2. Division of Clinical Pharmacology and Therapeutics, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Partner State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong, China; Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address: mycheung@hku.hk.
Abstract
BACKGROUND: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality. METHODS: We searched MEDLINE, EMBASE, the Cochrane database, and ClinicalTrials.gov up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients that reported MACE and deaths. Outcomes were compared with frequentist and Bayesian methods using R statistics. RESULTS: Seven RCTs with altogether 62,268 patients were included in the network meta-analysis. The SGLT-2 inhibitor and GLP-1 RAs reduced MACE (OR 0.85, 95%CI 0.73-0.99 and 0.89, 0.82-0.97, respectively) and all-cause mortality (0.67, 0.55-0.81 and 0.89, 0.80-0.99, respectively) compared to placebo. Furthermore, the SGLT-2 inhibitor reduced all-cause mortality compared to GLP-1 RAs (0.76, 0.61-0.94). In contrast, DPP-4 inhibitors did not reduce MACE or mortality compared to placebo and were associated with higher all-cause mortality compared to the SGLT-2 inhibitor (1.53, 1.24-1.89) and GLP-1 RAs (1.16, 1.01-1.33). CONCLUSIONS: All-cause mortality and MACE were reduced by the SGLT-2 inhibitor and GLP-1 RAs, but not DPP-4 inhibitors. The SGLT-2 inhibitor had the most beneficial impact on all-cause mortality. DPP-4 inhibitors showed no cardiovascular benefit and were inferior to the other two drug classes in preventing deaths.
BACKGROUND: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality. METHODS: We searched MEDLINE, EMBASE, the Cochrane database, and ClinicalTrials.gov up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabeticpatients that reported MACE and deaths. Outcomes were compared with frequentist and Bayesian methods using R statistics. RESULTS: Seven RCTs with altogether 62,268 patients were included in the network meta-analysis. The SGLT-2 inhibitor and GLP-1 RAs reduced MACE (OR 0.85, 95%CI 0.73-0.99 and 0.89, 0.82-0.97, respectively) and all-cause mortality (0.67, 0.55-0.81 and 0.89, 0.80-0.99, respectively) compared to placebo. Furthermore, the SGLT-2 inhibitor reduced all-cause mortality compared to GLP-1 RAs (0.76, 0.61-0.94). In contrast, DPP-4 inhibitors did not reduce MACE or mortality compared to placebo and were associated with higher all-cause mortality compared to the SGLT-2 inhibitor (1.53, 1.24-1.89) and GLP-1 RAs (1.16, 1.01-1.33). CONCLUSIONS: All-cause mortality and MACE were reduced by the SGLT-2 inhibitor and GLP-1 RAs, but not DPP-4 inhibitors. The SGLT-2 inhibitor had the most beneficial impact on all-cause mortality. DPP-4 inhibitors showed no cardiovascular benefit and were inferior to the other two drug classes in preventing deaths.
Authors: Bhavani Shankara Bagepally; Usa Chaikledkaew; Yogesh Krishnarao Gurav; Thunyarat Anothaisintawee; Sitaporn Youngkong; Nathorn Chaiyakunapruk; Mark McEvoy; John Attia; Ammarin Thakkinstian Journal: BMJ Open Diabetes Res Care Date: 2020-07