Older, cheaper drugs as safe as newer pills

Older, cheaper diabetes drugs are as safe and effective as newer ones, concludes an analysis that is good news for diabetics and may further hurt sales of Avandia, a blockbuster pill recently tied to heart problems.

The clear winner: metformin, sold as Glucophage and generically for about $100 a year. It works as well as other diabetes pills but does not cause weight gain or too-low blood sugar, the analysis found. It also lowers LDL or bad cholesterol.

“It looks to be the safest,” said Dr. Shari Bolen, a Johns Hopkins University researcher who led the review, which was published online Monday by the Annals of Internal Medicine.

Consumer Reports also published a consumer guide of the results. Besides metformin, it rates glipizide and glimepiride, sold as Amaryl and Glucotrol, as best bets.

“This is truly significant information for the millions of people with diabetes struggling to control their disease but also struggling with the high cost of their medications,” said Gail Shearer, project director of Consumer Reports Best Buy Drugs.

All diabetes pills can cause problems, so patients should pick the medication based on what side effects matter most in their own situation, the guide advises.

Diabetes afflicts more than 18 million Americans. Most have Type 2, which occurs when the body makes too little insulin or cannot use what it does produce. Being overweight raises this risk.

The federal Agency for Healthcare Research and Quality commissioned the analysis of diabetes drugs in 2005, long before a study published in May suggested Avandia, made by GlaxoSmithKline PLC, raised the risk of heart attacks. The new analysis says that evidence is insufficient to settle this issue.

The goal was to do the first in-depth comparison of oral medications that have come out in the last decade, as well as older ones like sulfonylureas that have been sold for 50 years. The report did not evaluate insulin or other injected diabetes drugs.

Researchers reviewed more than 200 published studies and obtained unpublished information from some drug companies and the federal Food and Drug Administration.

They found that most oral diabetes drugs lower “A1c” levels – a key measure of high blood sugar – by about one percentage point – from 8 to 7, for example (5 is normal for nondiabetics).

Taking two medications can improve blood sugar control, but also costs more and can raise the risk of side effects.

Despite heavy marketing for newer drugs, which cost as much as $262 a month, “we didn’t find any benefit” unless a patient could not tolerate an older one, Bolen said.

Other results:

¢ Metformin and acarbose (sold as Precose) do not increase weight. Others add 2 to 11 pounds.

¢ LDL or bad cholesterol drops by about 10 milligrams per deciliter of blood with metformin and increases by that amount with Avandia or Actos, made by Takeda Pharmaceuticals.

¢ Glimepiride, glipizide, glyburide and repaglinide lead to too-low blood sugar more often than other drugs do.

¢ Metformin and acarbose more often cause diarrhea and other digestive problems than the others.

¢ Actos and Avandia slightly raise HDL or good cholesterol.

¢ Actos and Avandia significantly raise the risk of heart failure.

Metformin is “an incredibly inexpensive generic drug, which is why we found it so appealing,” said Dr. David Nathan, diabetes chief at Massachusetts General Hospital.

But it can cause a rare but dangerous side effect called lactic acidosis, the buildup of lactic acid in the blood. It also should not be given to diabetics who have moderate kidney disease or heart failure. This is true of many other diabetes pills, too.