Teaching an Old Drug New Tricks: Can Paroxetine Ease the Burden of Cardiovascular Disease in Diabetes?

  1. Stephen B. Wheatcroft
  1. Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, University of Leeds, U.K.
  1. Corresponding author: Stephen B. Wheatcroft, s.b.wheacroft{at}

Diabetes doubles the risk of cardiovascular disease (CVD) independently of other risk factors (1). A 50-year-old with diabetes is likely to die, on average, 6 years earlier than a counterpart without diabetes, with vascular deaths being the major contributor to reduced survival (2). In keeping with the predicted rise in diabetes prevalence, the proportion of CVD deaths attributable to diabetes (currently 10% in developed countries [2]) is likely to increase substantially. Although intensive research efforts have identified the molecular mechanisms contributing to diabetes-related CVD, these discoveries have not been mirrored by major pharmaceutical advances. As a blockbuster drug to reduce CVD in diabetes has failed to emerge, other approaches need to be considered as a matter of urgency.

Although robust evidence supports the benefits of blood pressure reduction and lipid lowering in diabetes, the appropriateness of intensive glucose lowering as a tool to reduce cardiovascular risk is now questionable. In individuals newly diagnosed with diabetes, the UK Prospective Diabetes Study trial showed that intensive glycemic control with insulin or sulphonylurea resulted in a nonsignificant 16% risk reduction in myocardial infarction (3). Further, it was only after 10 years of follow-up that a 15% relative risk reduction emerged, suggesting a possible legacy effect of intensive control early in the disease process (4). In contrast, a series of large randomized trials investigating intensive glucose control in patients with diabetes of longer duration and/or established CVD has failed to demonstrate benefit. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation and Veterans Affairs …

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