Saxagliptin (ONGLYZA) - Another Diabetes Drug

Saxagliptin (ONGLYZA), a drug on the market since 2009 to treat type-2 diabetes, should not be taken until July 2016.

It was approved by the Food and Drug Administration (FDA) on July 31, 2009, and became the 20th drug, including insulin, to be sold for type-2 diabetes.

The FDA has identified three main safety concerns with saxagliptin: cardiovascular risks, liver toxicity and skin reactions. As a result of these concerns, the FDA has required the manufacturer to conduct postmarketing studies. The first of these is a randomized clinical trial to see if the drug causes major cardiovascular adverse reactions. The FDA also has required postmarketing studies to assess the risk of liver toxicity and severe skin reactions with the use of saxagliptin.

Saxagliptin is used for improving blood sugar control in adults with type-2 diabetes — in combination with diet and exercise. But saxagliptin and the other drugs marketed for blood sugar control will improve only the symptoms of type-2 diabetes, such as frequent urination and thirst.

Many doctors prescribe saxagliptin and other drugs of its kind thinking that they will reduce patients’ chances of heart attack and stroke, the major risks associated with diabetes. But no type-2 diabetes drug on the market today is allowed to claim that it can reduce heart attack and stroke.

The saxagliptin professional product label, or package insert, contains the following statement: “There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction [heart attack and stroke] with ONGLYZA or any other antidiabetic drug.”

Saxagliptin belongs to the new family of diabetes drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors. The first member of the DPP-4 class was sitagliptin (JANUVIA). It was approved in October 2006 and is now categorized as a Do Not Use drug on WorstPills.org. (See Worst Pills, Best Pills News, June 2007 and July 2008.)

Sitagliptin’s professional product label also carries a warning about reports of serious reactions in patients treated with the drug, such as swelling of areas of the skin, shedding of the skin and a potentially fatal skin condition called Stevens-Johnson syndrome. Allergic reactions — such as a rash, hives and swelling of the face, lips and throat — are signals to stop taking sitagliptin or saxagliptin and to seek medical attention right away.

A second DPP-4 inhibitor, vildagliptin (GALVUS), was approved for use in Europe in February 2008. It was denied approval in the U.S. because of questions of liver toxicity and reports that some patients developed serious allergic reactions and complications, including Stevens-Johnson syndrome.

A list of drugs approved for use in the U.S. for type-2 diabetes accompanies this article (see Table 1).

The FDA’s approval of saxagliptin

A very important fact for consumers to remember is that no law or regulation says a new drug must be safer or more effective than older drugs already on the market to gain FDA approval.

The FDA’s approval of type-2 diabetes drugs depends on the drug’s ability to reduce a blood chemical called hemoglobin A1c (HbA1c), which is a measure of blood sugar control compared to a placebo. The drug must be statistically better than a placebo to be granted approval for sale.

In two gold-standard randomized, controlled trials submitted to the FDA in support of saxagliptin’s approval, a total of 766 patients with type-2 diabetes inadequately controlled by diet and exercise (HbA1c between 7 percent and 10 percent) participated in 24-week trials evaluating the efficacy and safety of saxagliptin.

In the first trial, HbA1c was reduced on average by 0.5 percent in the group that received 5 milligrams of saxagliptin daily. In the second trial, the average reduction of HbA1c with saxagliptin given in a 5-milligram dose — where one group took the dose every morning and the other group took the dose every evening — was 0.4 percent and 0.3 percent, respectively, when compared to placebo.

What You Can Do

You should wait until July 2016 to take saxagliptin. Saxagliptin modestly reduces HbA1c, but there is no evidence to suggest that it reduces heart attack and stroke, the major risks of type-2 diabetes. And safety questions about the drug remain unanswered.

Seek immediate medical attention if you are taking saxagliptin or sitagliptin and experience allergic reactions such as rash, hives and swelling of the face, lips and throat.

Evolving evidence shows that a combination of aerobic and resistance training and a healthy diet can prevent and treat type-2 diabetes.

Consumers may report serious adverse events with products to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail, fax or phone.

• Online: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088

Table 1. Drugs Approved in the U.S. for Type-2 Diabetes

*Do Not Use on WorstPills.org
**Limited Use on WorstPills.org
***Do Not Use until Seven Years after FDA Approval

Updated 4/4/2012