Another possible explanation is an adverse effect from sulfonylurea drugs among patients on standard care. "Sulfonylureas may restrict the ability of the myocardium to adapt to ischemia, and it also prolongs the hypoglycemia," Dr. Rydén said. This explanation was endorsed by Dr. Peter Grant, a diabetologist and professor of medicine at the University of Leeds (U.K.). "It is difficult to believe that sulfonylureas are not having an adverse effect," he said as the designated discussant for Dr. Mellbin’s report. "These results tell us that hypoglycemia is an important determinant of outcome, and they raise questions about sulfonylureas," Dr. Grant said.
A third possible explanation is that increased mortality and poor cardiovascular prognosis and a tendency to develop hypoglycemia have a common, as-yet unidentified cause that has not been adjusted for in the models, Dr. Rydén said. "The relationship between severe hypoglycemia and cardiovascular outcomes is likely confounded by unmeasured risk factors," Dr. Mellbin said.
ORIGIN was funded by Sanofi, the company that markets insulin glargine (Lantus). Dr. Mellbin said that she has received lecture honoraria from Sanofi-Aventis and six other drug companies. Dr. Rydén said that he has received consulting and lecture honoraria from Sanofi-Aventis, Roche, Bristol-Myers Squibb, AstraZeneca, and Bayer. Dr. Grant said that he had no relevant disclosures.
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