Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis
Abstract Background Recent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a net...
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doaj-f0bac0d2c88d4489a0c370132ece5aec2020-11-25T03:49:16ZengBMCCardiovascular Diabetology1475-28402019-08-0118111310.1186/s12933-019-0916-zCardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysisYue Fei0Man-Fung Tsoi1Bernard Man Yung Cheung2Division of Clinical Pharmacology and Therapeutics, Department of Medicine, The University of Hong Kong, Queen Mary HospitalDivision of Clinical Pharmacology and Therapeutics, Department of Medicine, The University of Hong Kong, Queen Mary HospitalDivision of Clinical Pharmacology and Therapeutics, Department of Medicine, The University of Hong Kong, Queen Mary HospitalAbstract Background Recent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a network meta-analysis to compare the effect on cardiovascular outcomes among GLP-1 RAs, SGLT-2 and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods MEDLINE, EMBASE, Cochrane database, ClinicalTrials.gov, and congress proceedings from recent cardiology conferences were searched up to April 20, 2019. Cardiovascular outcome trials and renal outcome trials reporting cardiovascular outcomes on GLP-1 RAs, SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, all-cause mortality, hospitalisation for heart failure (HF), and renal composite outcome. ORs and 95% CI were calculated using random-effects models. Results Fourteen trials enrolling 121,047 patients were included. SGLT-2 inhibitors reduced cardiovascular deaths and all-cause deaths compared to placebo (OR 0.82, 95% CI 0.73–0.93 and OR 0.84, 95% CI 0.77–0.92) and DPP-4 inhibitors (OR 0.83, 95% CI 0.70–0.99 and OR 0.83, 95% CI 0.73–0.94), respectively. SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82–0.95 and OR 0.87, 95% CI 0.82–0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61–0.77 and OR 0.87, 95% CI 0.82–0.93), and renal composite outcome (OR 0.59, 95% CI 0.52–0.67 and OR 0.86, 95% CI 0.78–0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69–0.90) and renal composite outcome (OR 0.69, 95% CI 0.59–0.80) more than GLP-1 RAs. Only GLP-1 RAs reduced nonfatal stroke (OR 0.88, 95% CI 0.77–0.99). DPP-4 inhibitors did not lower the risk of these outcomes when compared to placebo and were associated with higher risks of MACE, hospitalisation for HF, and renal composite outcome when compared to the other two drug classes. Conclusions SGLT-2 inhibitors show clear superiority in reducing cardiovascular and all-cause deaths, hospitalisation for HF, and renal events among new antidiabetic drug classes. GLP-1 RAs also have cardiovascular and renal protective effects. DPP-4 inhibitors have no beneficial cardiovascular effects and are therefore inferior to the other two drug classes. SGLT-2 inhibitors should now be the preferred treatment for type 2 diabetes mellitus.http://link.springer.com/article/10.1186/s12933-019-0916-zAntidiabetic drugNetwork meta-analysisType 2 diabetes mellitusCardiovascular outcome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Fei Man-Fung Tsoi Bernard Man Yung Cheung |
spellingShingle |
Yue Fei Man-Fung Tsoi Bernard Man Yung Cheung Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis Cardiovascular Diabetology Antidiabetic drug Network meta-analysis Type 2 diabetes mellitus Cardiovascular outcome |
author_facet |
Yue Fei Man-Fung Tsoi Bernard Man Yung Cheung |
author_sort |
Yue Fei |
title |
Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
title_short |
Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
title_full |
Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
title_fullStr |
Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
title_full_unstemmed |
Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
title_sort |
cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis |
publisher |
BMC |
series |
Cardiovascular Diabetology |
issn |
1475-2840 |
publishDate |
2019-08-01 |
description |
Abstract Background Recent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a network meta-analysis to compare the effect on cardiovascular outcomes among GLP-1 RAs, SGLT-2 and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods MEDLINE, EMBASE, Cochrane database, ClinicalTrials.gov, and congress proceedings from recent cardiology conferences were searched up to April 20, 2019. Cardiovascular outcome trials and renal outcome trials reporting cardiovascular outcomes on GLP-1 RAs, SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, all-cause mortality, hospitalisation for heart failure (HF), and renal composite outcome. ORs and 95% CI were calculated using random-effects models. Results Fourteen trials enrolling 121,047 patients were included. SGLT-2 inhibitors reduced cardiovascular deaths and all-cause deaths compared to placebo (OR 0.82, 95% CI 0.73–0.93 and OR 0.84, 95% CI 0.77–0.92) and DPP-4 inhibitors (OR 0.83, 95% CI 0.70–0.99 and OR 0.83, 95% CI 0.73–0.94), respectively. SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82–0.95 and OR 0.87, 95% CI 0.82–0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61–0.77 and OR 0.87, 95% CI 0.82–0.93), and renal composite outcome (OR 0.59, 95% CI 0.52–0.67 and OR 0.86, 95% CI 0.78–0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69–0.90) and renal composite outcome (OR 0.69, 95% CI 0.59–0.80) more than GLP-1 RAs. Only GLP-1 RAs reduced nonfatal stroke (OR 0.88, 95% CI 0.77–0.99). DPP-4 inhibitors did not lower the risk of these outcomes when compared to placebo and were associated with higher risks of MACE, hospitalisation for HF, and renal composite outcome when compared to the other two drug classes. Conclusions SGLT-2 inhibitors show clear superiority in reducing cardiovascular and all-cause deaths, hospitalisation for HF, and renal events among new antidiabetic drug classes. GLP-1 RAs also have cardiovascular and renal protective effects. DPP-4 inhibitors have no beneficial cardiovascular effects and are therefore inferior to the other two drug classes. SGLT-2 inhibitors should now be the preferred treatment for type 2 diabetes mellitus. |
topic |
Antidiabetic drug Network meta-analysis Type 2 diabetes mellitus Cardiovascular outcome |
url |
http://link.springer.com/article/10.1186/s12933-019-0916-z |
work_keys_str_mv |
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