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Evaluating Cardiovascular Safety of Novel Therapeutic Agents for the Treatment of Type 2 Diabetes Mellitus

  • Hypertension (WB White, Section Editor)
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Abstract

Type 2 diabetes increases the risk of developing cardiovascular (CV) complications such as myocardial infarction, heart failure, stroke, peripheral vascular disease, and CV-associated mortality. Strict glycemic control in diabetics has shown improvement in microvascular complications related to diabetes but has been unable to demonstrate major effects on macrovascular complications including myocardial infarction and stroke. Conventional therapies for diabetes that include insulin, metformin, sulfonylureas (SU), and alpha-glucosidase inhibitors have limited and/or controversial data on CV safety based on observational studies not designed or powered to assess CV safety of these medications. In 2008, the US Food and Drug Administration (FDA) revised regulations for the approval of medications for type 2 diabetes by requiring that enough CV events are accrued prior to approval to rule out an upper 95 % confidence interval (95 % CI) for HR of 1.8 for CV events, followed by ruling out an upper 95 % CI for HR of 1.3 in the post-approval period. To date, novel diabetes therapies including peroxisome proliferator-activated receptor (PPAR) gamma agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP 1) analogs, and sodium-glucose transporter-2 (SGL2) inhibitors have been evaluated in CV safety trials. Results from the first major CV outcome studies in type 2 diabetes, SAVOR-TIMI 53 and EXAMINE, have shown that neither saxagliptin nor alogliptin had increases in major CV events relative to placebo in high-risk patients. Ongoing and future trials will elucidate the CV safety for other DPP-4 inhibitors compared to SUs and the GLP-1 agonists versus placebo.

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William Baker and Sidra Azim declare that they have no conflict of interest. William B. White reports personal fees from Takeda Development Center during the conduct of the EXAMINE Trial.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper (EXAMINE Trial), all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

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  1. Calhoun Cardiology Center and Department of Medicine, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030, USA

    Sidra Azim & William B. White

  2. Hartford Hospital and the University of Connecticut School of Pharmacy, Storrs, CT, 06269, USA

    William L. Baker

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  1. Sidra Azim
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Correspondence to William B. White.

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Azim, S., Baker, W.L. & White, W.B. Evaluating Cardiovascular Safety of Novel Therapeutic Agents for the Treatment of Type 2 Diabetes Mellitus. Curr Cardiol Rep 16, 541 (2014). https://doi.org/10.1007/s11886-014-0541-0

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