Trial looks at intensive insulin therapy risks

Intensive insulin therapy is used in many intensive care units around the world as a means to tightly regulate blood sugar.

Although labour intensive, it has been recommended as a standard of care for critically ill patients by many organizations including the American Diabetes Association and the American Association of Clinical Endocrinologists.

A randomized trial in 2001 reported that intensive insulin therapy significantly reduced hospital mortality, although subsequent trials have reported inconsistent effects on mortality and higher rates of severe hypoglycemia.

The CMAJ study includes data from 26 trials, including the NICE-SUGAR Study on intensive insulin therapy, an international, multicentre randomized trial that is the largest intensive insulin therapy trial to date. The NICE-SUGAR study is published online in the New England Journal of Medicine March 24, 2009 and March 26 for the print edition.

"By including the largest trial on intensive insulin therapy published to date, we provide the most current and precise estimate of the effect of intensive insulin therapy on vital status and hypoglycemia in the ICU setting," write Dr. Donald Griesdale, anesthesiologist and critical care physician at Vancouver General Hospital and clinical instructor at the University of British Columbia, and coauthors.

The CMAJ study looked at 26 trials involving 13 567 patients. There was a 6-fold increased risk of hypoglycemia compared to the control treatment.

The study was conducted by researchers from the University of British Columbia and Vancouver General Hospital, Vancouver, BC; Harvard School of Public Health, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Boston, Mass; Queen's University and Kingston General Hospital, Kingston, Ontario; McMaster University, Hamilton, Ontario; Royal North Shore Hospital and the University of Sydney, Australia.

"We suggest that policy makers reconsider recommendations promoting the use of intensive insulin therapy in all critically ill patients," write the authors. However, because the study included data from trials in different populations with varied illness severity, they "cannot exclude the possibility that some patients may benefit from intensive insulin therapy and be at less risk of hypoglycemic events."

In a related commentary (http://www.cmaj.ca/press/cmaj.090500.pdf), Dr. Greet Van den Berghe and colleagues argue that differences in specific elements of how intensive insulin therapy was delivered account for the varying findings of individual studies and that a single guideline for intensive insulin therapy applicable to all patients is not appropriate.