Hypoglycemia Associated with a Higher Risk of Cardiovascular Events

New results from the ORIGIN trial confirm that severe hypoglycemic events are associated with increased risk for cardiovascular events in patients with both and high cardiovascular risk, according to findings presented Sept. 2 at the ESC Congress 2013 in Amsterdam and simultaneously published in the European Heart Journal.

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The ORIGIN trial included 12,537 patients from 40 countries divided nearly evenly between treatment with insulin glargine and standard of care with oral agents. Patients on insulin glargine had significantly more episodes of both severe and non-severe hypoglycemia than patients on oral agents. Patients with non-severe hypoglycemia were not at increased risk for subsequent cardiovascular death or nonfatal MI or stroke during a mean follow-up of 6.2 years, said lead author Linda Mellbin, MD, Karolinska Institute, Stockholm, Sweden.

However, patients with severe hypoglycemia were at increased risk for subsequent cardiovascular death or nonfatal MI or stroke (HR 1.59, p<0.001), overall mortality (HR 1.75, p<0.001), cardiovascular death (HR1.71, p<0.001) and arrhythmic death (HR 1.77, p=0.007). Patients in the standard treatment group were at two-to-three times the risk for subsequent cardiovascular events even though they had fewer episodes of severe hypoglycemia than insulin glargine patients.

"In light of the more frequent hypoglycemia in the insulin group, hypoglycemia caused by insulin glargine-mediated glucose lowering is unlikely to be the cause of cardiovascular outcomes," Dr. Mellbin concluded. "The relationship between severe hypoglycemia and cardiovascular outcomes is likely due to confounding by unmeasured risk factors for cardiovascular outcomes."

Keywords: Stroke, Follow-Up Studies, Insulin, Long-Acting, Standard of Care, Cardiovascular Diseases, Risk Factors, Hypoglycemic Agents, Hypoglycemia

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