CV Safety of Diabetes Drugs: What Do We Know?

Silvio E. Inzucchi, MD


April 28, 2015

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Hi. I'm Dr Silvio Inzucchi, professor of medicine at Yale University.

I was recently in sunny San Diego, at the 2015 Endocrine Society 97th Annual Meeting & Expo.[1] I spoke in a plenary session about type 2 diabetes and cardiovascular (CV) disease ("Antihyperglycemic Therapy and Cardiovascular Disease: In Search of the Holy Grail").[1]

The point I tried to make and that I want to make here is that after many decades of treating patients with type 2 diabetes with oral and injectable agents, we still don't know much about the impact of these medications on CV events.

Most experts agree that metformin probably has a CV benefit,[2] but beyond that, the data are conflicting. There is some lingering concern about the CV safety of the sulfonylureas,[3] and the thiazolidinediones (TZDs) have had an interesting history in terms of effects on the heart, some data suggesting beneficial[4] and other deleterious effects.[5] The newer categories of antidiabetic medications, such as the incretin-based therapies, are still being studied.[6,7,8]

The first glimpse that we have of the dipeptidyl peptidase 4 (DPP-4) inhibitors suggests that these drugs are neutral in terms of CV events.[9] We're eagerly awaiting the upcoming trials from the glucagon-like peptide 1 (GLP-1)[10] receptor agonist category, as well as the sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors.[11] There is something to suggest that these medications may have an intrinsic CV benefit, either by direct effects on the heart (the GLP-1 receptor agonists) or indirect effects, by modulating risk factors for CV disease (both the GLP-1 receptor agonists and the SGLT2 inhibitors).

We will have to wait until results of the studies with these agents are disclosed to see whether any of these newer categories of drugs might have any beneficial impact on the major killer of our patients with type 2 diabetes: CV disease.

One of the points I'd like to make is that many of the studies under way are relatively short compared with other CV outcome trials. Therefore, it would be somewhat optimistic to suggest that any of these trials might actually show a CV benefit. Most of these studies are conducted over a period of perhaps 2-3 years of mean exposure. And I think—because of the atherosclerotic process as it relates to hyperglycemia—we may need a longer duration of exposure before we know whether any of these compounds have an intrinsic, beneficial effect on CV events.


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