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A review of cardiovascular outcome trials in type 2 diabetes
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Abstract
Type 2 diabetes is a complex metabolic disorder associated with a high risk of cardiovascular complications. In December 2008, due to concerns about the cardiac safety of antihyperglycaemic therapies, the Food and Drug Administration (FDA) published a new guidance on special requirements for the demonstration of cardiovascular safety for these medications. In 2012, similar recommendations were made for antidiabetic drug manufacturers by the European Medicines Agency (EMA). Since then, both FDA and EMA recommendations have been applied in cardiovascular outcome trials (CVOTs) for several new antihyperglycaemic drugs. Unlike conventional trials, CVOTs are usually placebo controlled, non-inferiority trials that examine the cardiovascular safety of a drug compared to standard of care in large cohorts of patients with high cardiovascular risk or established cardiovascular disease. Patients in CVOTs are also monitored for a longer observation period than in typical randomised controlled trials to provide data on long-term cardiovascular risk. To date, nine CVOTs involving patients with type 2 diabetes have been completed, and at least 13 are still ongoing. These studies focus on a variety of antihyperglycaemic drugs, including incretin-based agents, sodium-glucose cotransporter 2 inhibitor (SGLT-2) inhibitors, and insulin formulations. This article takes a critical look at these CVOTs and summarises the results of the completed trials.
Abstract
Type 2 diabetes is a complex metabolic disorder associated with a high risk of cardiovascular complications. In December 2008, due to concerns about the cardiac safety of antihyperglycaemic therapies, the Food and Drug Administration (FDA) published a new guidance on special requirements for the demonstration of cardiovascular safety for these medications. In 2012, similar recommendations were made for antidiabetic drug manufacturers by the European Medicines Agency (EMA). Since then, both FDA and EMA recommendations have been applied in cardiovascular outcome trials (CVOTs) for several new antihyperglycaemic drugs. Unlike conventional trials, CVOTs are usually placebo controlled, non-inferiority trials that examine the cardiovascular safety of a drug compared to standard of care in large cohorts of patients with high cardiovascular risk or established cardiovascular disease. Patients in CVOTs are also monitored for a longer observation period than in typical randomised controlled trials to provide data on long-term cardiovascular risk. To date, nine CVOTs involving patients with type 2 diabetes have been completed, and at least 13 are still ongoing. These studies focus on a variety of antihyperglycaemic drugs, including incretin-based agents, sodium-glucose cotransporter 2 inhibitor (SGLT-2) inhibitors, and insulin formulations. This article takes a critical look at these CVOTs and summarises the results of the completed trials.
Keywords
type 2 diabetes mellitus; cardiovascular disease; hyperglycaemia
About this articleTitle
A review of cardiovascular outcome trials in type 2 diabetes
Journal
Issue
Article type
Review paper
Pages
424-440
Published online
2018-08-21
Page views
2824
Article views/downloads
2835
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2018;69(4):424-440.
Keywords
type 2 diabetes mellitus
cardiovascular disease
hyperglycaemia
Authors
Katarzyna Cypryk
Piotr Małecki
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