Side Effects May Sway Drug Choices for Tough-to-Manage Diabetes

THURSDAY May 19, 2011 -- When someone with type 2 diabetes needs a third medication to control blood sugar levels, the choice may come down to which drug has the least undesirable side effects, because the available medications all lower blood sugar in a similar manner.

That's the conclusion of a new review of data that shows there were no great differences in the ability of various classes of medication to lower blood sugar among type 2 diabetics, when used as "third-line" treatment (after a first and second drug don't suffice).

However, the study also found that some medications could cause weight gain, and some caused episodes of low blood sugar levels (hypoglycemia).

In any event, "type 2 diabetes is a progressive disease and most patients will need the combination of two or three anti-hyperglycemic agents to reach good glucose control in the long-term," noted the study's lead author, Dr. Jorge Gross, a professor of medicine at the Hospital de Clinicas de Porto Alegre, Brazil.

"The choice of the third agent should be individualized according to the characteristics of the patients and the undesirable effects of the medications, so you can't elect one agent to be used in all patients with type 2 diabetes," he explained.

The study results were published in this week's issue of the Annals of Internal Medicine.

Metformin, an older medication that's available as a generic, is generally recommended as a first-line treatment for type 2 diabetes, along with physical activity and diet changes. If metformin and lifestyle changes fail to control blood sugar well, a second drug is generally added.

For this study, the researchers chose the commonly used combination of metformin and a sulfonylurea. Drugs in the sulfonylurea class are usually available as generics and include: glyburide, glipizide, chlorpropamide, tolbutamide and tolazamide.

"This study looked at what's probably the most common combination of diabetes medications, but even the second-line therapy should be individualized based on the patient's needs," said Dr. Robert Henry, president of medicine and science for the American Diabetes Association.

Third-line medications in the current study included alpha-glucosidase inhibitors (acarbose), thiazolidinediones (which include Avandia and Actos), glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors.

The review included 18 clinical trials with a total of more than 4,500 people. The studies lasted an average of more than 31 weeks.

When the researchers compared reductions in hemoglobin A1C (HbA1C) levels, they found no statistically significant differences between the third-line medications. HbA1C is a blood test that measures long-term (about two to three months) blood sugar levels.

Weight gain was more common in people taking insulin or a thiazolidinedione. The average weight gain for those on insulin was about six pounds, according to the study. For those on thiazolidinediones, the average weight gain was more than nine pounds.

An average weight loss of 3.6 pounds was seen in people taking GLP-1 agonists, reported the study. Insulin was most likely to reduce blood sugar levels too much, raising the odds for hypoglycemia, according to the study.

Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City, stressed, however, that "these are mostly drug company studies, and they're not long-term studies."

This review "shows that giving a third agent can help, and it also shows us that these medications have both good and bad effects," he said. "But we really need long-term studies on combinations that aren't sponsored by the pharmaceutical companies."

The bottom line, according to Zonszein: "Each patient should be treated individually. Are they obese? If yes, there are certain medications like insulin and thiazolidinediones that may cause weight gain we don't want."

When it comes to third-line agents, Henry said, another factor may be price. Some medications aren't always available in generic form, which may make them significantly more expensive.

If you have specific concerns, such as weight gain or cost, Henry said it's important to bring these concerns to your doctor's attention when you're talking about adding another diabetes medication.

"If a third medication is needed because glucose control isn't adequate, get one that's tailored to your unique needs," he advised.

"We think that the results of this study offer a wide range of choices of anti-hyperglycemic agents that might be used as the third option in patients with type 2 diabetes not controlled using metformin and sulphonylurea based on efficacy. The final decision would depend on the effects in weight and risk of hypoglycemic episodes," said Gross.

More information

Learn more about diabetes medications from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Posted: May 2011


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