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Taking metformin and insulin in conjunction raises mortality risk for diabetes patients


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(NaturalNews) Combining the diabetes drug metformin with insulin significantly increases patients' risk of death, according to a study conducted by researchers from Vanderbilt University and published in a diabetes-themed issue of JAMA on June 11.

The researchers compared the use of metformin in conjunction with insulin to the use of the same drug in conjunction with antidiabetic drugs in the sulfonylurea class.

"These findings require further investigation to understand risks associated with insulin use in these patients and call into question recommendations that insulin is equivalent to sulfonylureas for patients who may be able to receive an oral agent," the researchers wrote.

Higher risk for no benefit

According to both the American Diabetes Association and the European Association for the Study of Diabetes, metformin is the preferred first-line treatment -- along with lifestyle changes such as improving diet and exercise -- for diabetic patients with intact kidney function. If these measures alone are not enough to achieve treatment goals, doctors will often supplement metformin with a secondary medication. There is no scientific or medical consensus, however, on which secondary medication is safest or most effective.

Sulfonylurea drugs are popular as a secondary medication, but in recent years the use of insulin has also become popular. Limited clinical trials have suggested that combining metformin with insulin can help achieve fast and flexible control of patients' blood sugar levels.

To evaluate these two separate approaches, researchers examined national Veterans Health Administration, Medicare and National Death Index databases for records on 178,341 diabetic veterans. All the patients had been initially treated with metformin between the years 2001 and 2008, and many were later treated with either sulfonylurea or insulin. Patients took metformin for a median length of 14 months before receiving a secondary medication, and the median follow-up time after this point was also 14 months.

The researchers found that patients who received insulin were significantly more likely to die during the study period than sulfonylurea patients.

"Our study suggests that intensification of metformin with insulin among patients who could add a sulfonylurea offers no advantage in regard to risk of cardiovascular events and is associated with some risk," the researchers wrote.

Previous findings had suggested that insulin might also be more likely to increase the rate of stroke and heart attack, a finding that this study supported. Likewise, no improved treatment outcomes were seen from insulin, compared with alternatives.

"Our finding of a modestly increased risk of a composite of cardiovascular events and death in metformin users who add insulin compared with sulfonylurea is consistent with the available clinical trial and observational data," the researchers wrote. "None of these studies found an advantage of insulin compared with oral agents for cardiovascular risk, and several reported increased cardiovascular risk or weight gain and hypoglycemic episodes, which could result in poorer outcomes."

Doctor education needed

In an accompanying editorial, Monika M. Safford, MD, of the University of Alabama-Birmingham praised the researchers for conducting a study comparing the effectiveness of separate treatments.

"Comparative effectiveness research is creating new challenges as it generates much needed new evidence," Safford wrote.

"Some of the creativity being brought to bear on advancing methods of analysis may also be needed to advance methods of communicating both methods and results to practicing clinicians, and perhaps more importantly, to the patients who are facing decisions that may (or may not) have profound implications for their health and well-being."

Diabetes is a major public health crisis, affecting more than 25 million people in the United States alone. It is the seventh-leading cause of death, and the foremost cause of adult blindness and kidney failure.

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