October 09, 2013
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Rosiglitazone/exenatide decreased adverse CV events in patients with diabetes

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Combination therapy through a systems biology approach could decrease adverse events in patients with diabetes. In particular, researchers found that adding a second drug to rosiglitazone could significantly decrease adverse cardiovascular events, according to data.

“Through this analysis, we found that exenatide significantly reduces reporting of both [myocardial infarction] and stroke,” Ravi Iyengar, PhD, the Dorothy H. and Lewis Rosenstiel professor of pharmacology and systems therapeutics, and director of the Systems Biology Center New York at the Icahn School of Medicine at Mount Sinai, and colleagues wrote. “Because exenatide works well clinically to reduce blood glucose with metformin or rosiglitazone, co-prescription of exenatide with rosiglitazone could be more beneficial than co-prescription of warfarin or other anticoagulants that have no effect on blood glucose, although this has to be balanced with increased risk of pancreatitis associated with exenatide.”

Ravi Iyengar, PhD 

Ravi Iyengar

Iyengar and colleagues used the FDA’s Adverse Event Reporting System (FAERS; n=3,918,732), Mount Sinai’s hospital electronic health records database (n=34) and an animal model to determine the effects of this combination therapy.

Using FAERS, research confirmed that rosiglitazone (Avandia, GlaxoSmithKline) increased reports of MI. When exenatide (Byetta, Bydureon; Amylin) was added, reports of MI and stroke significantly decreased, according to data.

“The beneficial effects of rosiglitazone and exenatide are not unique,” Iyengar said in a press release. “We found nearly 19,000 other drug combinations in the FDA database, where the second drug appears to reduce a wide range of side effects of the first drug. Other beneficial effects were demonstrated when lisinopril was added to a statin, where the rate of statin-associated rhabdomyolysis, a kind of muscle tissue wasting, declined; when an H2 antagonist was added to [selective serotonin reuptake inhibitors], it reduced completed suicide.

“Big data systems have a wealth of data, and when studied appropriately, can point to potentially safer combinations,” Iyengar said. “As an end in themselves, big data analyses must be considered preliminary, but findings can point to potentially safer combinations that can subsequently be tested in clinical trial. We may be able to use FDA-approved drugs to prevent adverse events.”

Disclosure: Iyengar reports support for one postdoctoral position from GlaxoSmithKline. All other researchers report no relevant financial disclosures.