Cardiovascular Outcomes Comparison of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylurea as Add-on Therapy for Type 2 Diabetes Mellitus: a Meta-Analysis

Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin. After searchi...

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Published inJournal of lipid and atherosclerosis Vol. 10; no. 2; pp. 210 - 222
Main Authors Jeon, Won Kyeong, Kang, Jeehoon, Kim, Hyo-Soo, Park, Kyung Woo
Format Journal Article
LanguageEnglish
Published Korea (South) Korean Society of Lipidology and Atherosclerosis 01.05.2021
한국지질동맥경화학회
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ISSN2287-2892
2288-2561
DOI10.12997/jla.2021.10.2.210

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Abstract Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin. After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected. Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; =0.811; I =0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; =0.517; I =0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; <0.001; I =98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; <0.001; I =94.7, respectively). As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.
AbstractList Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin.OBJECTIVERecent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin.After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.METHODSAfter searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; p<0.001; I2=94.7, respectively).RESULTSRegarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; p<0.001; I2=94.7, respectively).As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.CONCLUSIONAs add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.
Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin. After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected. Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; =0.811; I =0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; =0.517; I =0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; <0.001; I =98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; <0.001; I =94.7, respectively). As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.
Objective: Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin. Methods: After searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected. Results: Regarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98–1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83–1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53–9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07–2.29; p<0.001; I2=94.7, respectively). Conclusion: As add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs. KCI Citation Count: 0
Author Kim, Hyo-Soo
Park, Kyung Woo
Jeon, Won Kyeong
Kang, Jeehoon
AuthorAffiliation Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Keywords DPP4 inhibitor
Sulfonylurea compounds
Diabetes mellitus
Cardiovascular risk
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Snippet Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through...
Objective: Recent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review...
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Title Cardiovascular Outcomes Comparison of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylurea as Add-on Therapy for Type 2 Diabetes Mellitus: a Meta-Analysis
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