Old Diabetes Drug Has Advantages

Report: Metformin Effective With Fewer Side Effects Than Newer Drugs

Medically Reviewed by Brunilda Nazario, MD on July 16, 2007
From the WebMD Archives

July 16, 2007 -- Most type 2 diabetes drugs are equally effective for lowering blood sugar, but the generic drug metformin has fewer side effects than several newer, pricier medications, a government report finds.

Metformin users are less likely to gain weight than type 2 diabetes patients who take Avandia, Actos, or other newer medications, researchers concluded, and they are more likely to show improvements in so-called "bad" cholesterol.

The report was issued by the Agency for Healthcare Research and Quality (AHRQ), a division of the Department of Health and Human Services.

Researchers from Johns Hopkins University’s Evidence-based Practices Center reviewed 216 previously published studies in their effort to compare the effectiveness, risks, and costs of older and newer diabetes pills.

The study, which was made public today, will appear in the Sept. 18 issue of the Annals of Internal Medicine.

Diabetes Drugs: Old and New

All diabetes medications help to lower blood sugar, but they work in different ways. Metformin and drugs in the class known as sulfonylureas, such as Glipizide or Glyburide, are among the least-expensive oral diabetes medications because generic versions are now available.

The newer oral medications Avandia (by GlaxoSmithKline) and Actos (by Takeda Pharmaceuticals) -- both in the drug class thiazolidinedione (TDZ) -- are now among the most widely prescribed diabetes drugs.

Among the highlights of the report:

  • Metformin was one of the few diabetes drugs not associated with an increase in weight. The report noted that other widely prescribed diabetes drugs have been shown to increase body weight by an average of 2 to 11 pounds.
  • Use of metformin was associated with a decrease in blood levels of low-density lipoprotein, or "bad" cholesterol, while use of the TDZ class of drugs raised levels good cholesterol and had a harmful effect on LDL "bad" cholesterol.
  • Amaryl, Glucotrol, and other sulfonylurea drugs were more likely to cause unsafe drops in blood sugar (hypoglycemia) than other diabetes drugs.
  • Patients on metformin or the drug acarbose complained of diarrhea and other gastrointestinal problems more than users of other drugs. Patients who took only metformin were more likely to experience these digestive problems than patients who took lower doses of metformin in combination with other diabetes drugs.
  • Use of Avandia and Actos was associated with a greater risk of congestive heart failure.

Diabetes Drugs and the Heart

Concerns about heart failure risk led the FDA to announce last month that labels for Avandia and Actos will soon carry a "black box" warning to alert doctors and patients to the risk. A highly publicized study recently linked Avandia to an increased risk of death from heart attacks, but the drug's manufacturer has challenged the findings.

In testimony before a congressional committee in June, a GlaxoSmithKline spokesman said there is no evidence that Avandia carries more heart risk than other drugs of its class. And an interim report from an ongoing company-sponsored study assessing Avandia's impact on the heart found the data on heart attack risk to be inconclusive.

The AHRQ report came to the same conclusion.

The researchers wrote that other than an established increase in heart failure risk for the TDZs, the data are insufficient to show that Avandia users are more likely than users of other diabetes drugs to have heart attacks.

They call for high-quality studies to give doctors and patients a better idea of the risks and benefits associated with all oral diabetes drugs, either taken alone or in combination.

A spokesperson for Actos manufacturer Takeda Pharmaceuticals declined to comment on the report.

A spokeswoman for GlaxoSmithKline tells WebMD that there is "absolutely no new data" in the review. She says reviewers failed to include critical studies in their report, including the company's own ongoing investigation of the long-term impact of Avandia on the heart.

Interim results from that trial, "add to the weight of evidence, from both previously published long-term clinical trials and other studies, that the overall [cardiovascular] safety profile of Avandia is comparable to traditional antidiabetes treatments," she says.

Metformin Used First

Jean Slutsky, MSPH, of the AHRQ tells WebMD that the new report adds weight to a 2005 recommendation from the American Diabetes Association and the International Diabetes Federation identifying metformin as the initial treatment for newly diagnosed, non-insulin dependent diabetes.

"Metformin does offer some advantages over some of the other drugs prescribed for type 2 diabetes," she says. "But not all patients are alike, and some drugs may be tolerated better by certain patients."

American Diabetes Association president Larry C. Deeb, MD, agrees the new report should make doctors take a new look at some of the older diabetes drugs.

He adds that none of the oral diabetes drugs is particularly effective for treating severe insulin resistance and doctors often wait too long to put patients on insulin.

"It is not fair to patients with very out of control glucose levels to expect their blood sugar to return to normal with oral treatments, but that is happening all the time," he tells WebMD. "Doctors are afraid of insulin, and as a result many patients are living with out of control diabetes."

Show Sources

SOURCES: Bolen, Shari, MD, MPH, "Agency for Healthcare Research and Quality (AHRQ) review of oral medications for type 2 diabetes, Annals of Internal Medicine, Sept. 18, 2007; online edition. Jean Slutsky, MSPH, head of the AHRQ Effective Healthcare Program. Larry C. Deeb, MD, president, American Diabetes Association; medical director, Diabetes Center, Tallahassee Memorial Hospital, Tallahassee, Fla. Nissen et al. New England Journal of Medicine, June 14, 2007; vol 356.

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