Clinical research study
Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes

https://doi.org/10.1016/j.amjmed.2017.04.008Get rights and content
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Abstract

Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)—namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear. Although current antidiabetic drugs are highly effective for the management of hyperglycemia, most T2DM patients remain exposed to a substantial and concrete risk of CVD. Over the last decade many glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD. Noteworthy, most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive glycemic control. The recent trials Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA-REG OUTCOME); Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6); Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER); and Insulin Resistance Intervention After Stroke (IRIS) have shed some light on this important clinical issue, thus showing a convincing effect of empagliflozin, liraglutide, and pioglitazone on CVD outcomes. Here we provide a critical and updated overview of the main glucose-lowering agents and their risk/benefit ratio for the prevention of CVD in patients with T2DM.

Keywords

Cardiovascular disease
Glucose-lowering therapy
Type 2 diabetes treatment

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Funding: The present work was supported by the Swiss National Science Foundation (TFL) and the Foundation for Cardiovascular Research – Zurich Heart House, Zurich, Switzerland. Copyright permission and publication costs were supported by Boehringer Ingelheim Pharmaceuticals, Inc. FP is the recipient of a Sheikh Khalifa’s Foundation Assistant Professorship at the Faculty of Medicine, University of Zurich. The other author received no direct compensation related to the development of the manuscript.

Conflict of Interest: The authors have no actual or potential conflict of interest, including any financial, personal, or other relationships with other people or organizations.

Authorship: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development, and approved the final version that reflects the authors' interpretations and conclusions. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

This article is co-published in The American Journal of Medicine (Vol. 130, Issue 6S, June 2017) and The American Journal of Cardiology (Vol. 120, Issue 1S, July 1, 2017).