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Drug Combo Linked to Increased Health Risks

Tara Dairman

August 15, 2008

According to an evaluation of multiple studies, taking a combination of two common types of Type 2 diabetes drugs may be linked to an increased risk of dying or ending up in the hospital due to cardiovascular disease.

The new study, published in the August issue of Diabetes Care, pooled data from nine large studies with more than 101,000 total participants with Type 2 diabetes. These participants had been treated with diet alone, metformin (Glucophage and other brand names), a sulfonylurea drug, or a combination of metformin and a sulfonylurea.

The researchers found that people who had been treated with metformin and a sulfonylurea had a significantly higher risk of dying or being hospitalized due to cardiovascular disease than any of the other groups.

However, people on the combination drug therapy did not have a higher risk of dying from cardiovascular disease or from any cause when risk of death was considered on its own. Only when risk of death was combined with risk of hospitalization did the researchers see a higher risk with combination drug therapy.

Trying to explain their findings, the researchers offered the following thoughts:

  • People who need combination therapy to control their blood glucose levels are likely to have more rapidly-progressing diabetes or have had diabetes for a longer period of time (or both); it may be the more advanced diabetes, rather than the treatment, that raises risks.
  • Weight gain (which is associated with sulfonylureas) may increase some risks, even when the drug is used in combination with metformin, which is not associated with weight gain.
  • Sulfonylureas can cause hypoglycemia, and using them in combination with metformin may make hypoglycemic episodes harder to recover from because metformin prevents the liver from making extra glucose. Hypoglycemia may increase cardiovascular risk.

An analysis of several observational studies like this one doesn’t carry as much weight as a full-scale clinical trial, and the researchers point out that its results should not be used as a basis for treatment decisions. Instead, they propose further studies in this area to determine the safest and most effective ways to manage diabetes.



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