AIM: Benefits of inpatient intensive insulin therapy are unclear

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No consistent evidence demonstrates that intensive insulin therapy targeted to strict glycemic control compared with less strict glycemic control improves health outcomes in hospitalized patients, based on a systematic review published Feb. 15 in the Annals of Internal Medicine. Furthermore, the researchers found that intensive insulin therapy is associated with an increased risk for severe hypoglycemia. These findings have ganered immediate reaction from various medical associations.

The benefits and harms of intensive insulin therapy titrated to strict glycemic targets in hospitalized patients remain uncertain, wrote Devan L. Kansagara, MD, and colleagues from Oregon Health & Science University, Portland Veterans Affairs Medical Center and Portland Diabetes & Endocrinology Center in Portland, Ore.

Therefore, in a meta-analysis of 21 trials in intensive care unit, perioperative care, MI and stroke or brain injury settings, two reviewers independently abstracted data from each study on sample, setting, glycemic control interventions, glycemic targets, mean glucose levels achieved and outcomes. They grouped the results by patient population or setting.

The researchers used a random-effects model to combine trial data on short-term mortality ( <28 days), long-term mortality (90 or 180 days), infection, length of stay and hypoglycemia. The Grading of Recommendations Assessment, Development and Evaluation system was used to rate the overall body of evidence for each outcome.

Kansagara and colleagues found that intensive insulin therapy did not affect short-term mortality (relative risk, 1.0). However, they also found that no consistent evidence showed that intensive insulin therapy reduced long-term mortality, infection rates, length of stay or the need for renal replacement therapy.

In addition, they found that no evidence of benefit from intensive insulin therapy was reported in any hospital setting, although the best evidence for lack of benefit was in intensive care unit settings. Data combined from 10 trials showed that intensive insulin therapy was associated with a high risk for severe hypoglycemia (relative risk, 6.0). Risk for intensive insulin therapy-associated hypoglycemia was increased in all hospital settings.

The authors acknowledged that methodological shortcomings and inconsistencies limited the data in peri-operative care, MI and stroke or brain injury settings, adding that differences in insulin protocols as well as patient and hospital characteristics may affect generalizability across treatment settings.

Kansagara and colleagues concluded that the consequences of inpatient hypoglycemia are “unclear.” They continued: "Many institutions are likely to pursue less aggressive glycemic control, but the health benefits of achieving moderate blood glucose level targets, such as 7.8 to 11.1 mmol/L (140 to 200 mg/dL), should be examined. Future studies also should evaluate the cost and patient, nurse and physician acceptance of implementing insulin infusion protocols in hospitalized standards.”

Various medical societies have issued responses to the findings and conclusions of the study authors. “Hyperglycemia in hospitalized patients is common and associated with increased risk of infection, mortality, and increased cost,” said Daniel Einhorn, MD, president of the American Association of Clinical Endocrinologists (AACE). “Although near normalization of glucose in these patients appears to be of no greater benefit than moderate glycemic targets, ignoring hyperglycemia in this population is no longer acceptable.”

“Both over treatment and under treatment of hyperglycemia in hospitalized patients are patient safety issues,” said Robert R. Henry, MD, president of medicine and science for the American Diabetes Association (ADA). “Coordinated, interdisciplinary teams have been shown to achieve both safe and effective control of hyperglycemia in hospitalized patients.”

The U.S. Department of Veterans Affairs Health Services Research and Development Service provided funding for the review.