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Mayo Clin Proc. 2010 January; 85(1): 99.
PMCID: PMC2800294

Role of Oral Agents in Improving Cardiovascular Prognosis in Diabetes Mellitus

To the Editor: In their otherwise excellent review entitled “Primary and Secondary Prevention of Cardiovascular Diseases: A Practical Evidence-Based Approach,” O'Keefe et al1 highlight the increased risk associated with diabetes mellitus (DM). They state that optimization of the dismal cardiovascular prognosis associated with DM requires aggressive risk factor treatment. The first risk factor they address is glycemic control. To support their contention, they cite the UK Prospective Diabetes Study, indicating that the trial showed sustained reductions in retinopathy, nephropathy, and neuropathy. Notably absent from that list is macrovascular cardiovascular disease. The authors then recommend use of oral agents that have a limited risk of hypoglycemia, such as metformin, dipeptidyl peptidase-4 inhibitors, glucosidase inhibitors, and thiazolidinediones. They do not include sulfonylureas, apparently because of the propensity to cause hypoglycemia, but then state that insulin, the leading culprit in hypoglycemia, is often needed to achieve adequate control.

What the authors fail to do is to present evidence, as the title of the article suggests, to support this recommendation. We have recently seen in the Veterans Affairs Diabetes Study that tighter control of DM with oral agents and insulin does not lower the rate of cardiovascular events in high-risk patients.2 Many of the agents cited have been approved by the Food and Drug Administration on the basis of their ability to lower hemoglobin A1c levels, a surrogate marker for DM; no data exist that they prevent any important patient-oriented outcomes, including cardiovascular disease.

In contrast, the authors did provide studies that support control of lipids and blood pressure, and data are clear that better control leads to better cardiovascular outcomes.

Evidence-based cardiovascular prevention recommendations should be based on evidence. Until there is evidence that each of the agents mentioned by O'Keefe et al is effective in reducing cardiovascular disease, such agents should not be included in an authoritative review. Adding cost, drug interactions, and adverse effects to a patient's regimen is not good medicine. Physicians need to be guided by data, not conventional wisdom, no matter how much intuitive sense it may make.


1. O'Keefe JH, Carter MD, Lavie CJ. Primary and secondary prevention of cardiovascular diseases: a practical evidence-based approach. Mayo Clin Proc 2009;84(8):741-757 [PMC free article] [PubMed]
2. Duckworth W, Abraira C, Moritz T, et al. VADT Investigators Glucose control and vascular complications in veterans with type 2 diabetes [published corrections appear in N Engl J Med. 2009;361(10):1024-1025 and 2009;361(10):1028] N Engl J Med 2009. January8;360(2):129-139 Epub 2008 Dec 17 [PubMed]

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