Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.

In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and card...

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Main Authors: Gyeongsil Lee, Seung-Won Oh, Seung-Sik Hwang, Ji Won Yoon, Sungchan Kang, Hee-Kyung Joh, Hyuktae Kwon, Jeehyun Kim, Danbee Park
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5444626?pdf=render
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spelling doaj-1da750cb2bc44309a5b8e66f59cede9c2020-11-25T02:05:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017764610.1371/journal.pone.0177646Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.Gyeongsil LeeSeung-Won OhSeung-Sik HwangJi Won YoonSungchan KangHee-Kyung JohHyuktae KwonJeehyun KimDanbee ParkIn the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.http://europepmc.org/articles/PMC5444626?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Gyeongsil Lee
Seung-Won Oh
Seung-Sik Hwang
Ji Won Yoon
Sungchan Kang
Hee-Kyung Joh
Hyuktae Kwon
Jeehyun Kim
Danbee Park
spellingShingle Gyeongsil Lee
Seung-Won Oh
Seung-Sik Hwang
Ji Won Yoon
Sungchan Kang
Hee-Kyung Joh
Hyuktae Kwon
Jeehyun Kim
Danbee Park
Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
PLoS ONE
author_facet Gyeongsil Lee
Seung-Won Oh
Seung-Sik Hwang
Ji Won Yoon
Sungchan Kang
Hee-Kyung Joh
Hyuktae Kwon
Jeehyun Kim
Danbee Park
author_sort Gyeongsil Lee
title Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
title_short Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
title_full Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
title_fullStr Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
title_full_unstemmed Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
title_sort comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: a network meta-analysis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2017-01-01
description In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.
url http://europepmc.org/articles/PMC5444626?pdf=render
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