The FDA has approved liraglutide (Victoza), a once-daily injection of a glucagon-like peptide-1 (GLP-1) analogue, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.
But the agency cautioned that the drug should not be used as first-line therapy until more research has been done on the risk of thyroid tumors or medullary thyroid cancer.
Last year, an FDA advisory committee came to a split vote over whether to approve liraglutide because of an increased risk of thyroid cancer in animal models. (See Tumor Data May Block Approval for Diabetes Drug Liraglutide)
The agency has required drugmaker Novo Nordisk to conduct a five-year epidemiological study using a health claims database to evaluate thyroid and other cancer risks. It must also establish a cancer registry to monitor the rate of medullary thyroid cancer in the U.S. over the next 15 years.
The FDA also warned against use of the drug in patients with a family history of medullary thyroid cancer or a genetic condition known as Multiple Endocrine Neoplasia syndrome type 2.
In a statement, Novo Nordisk said in its phase III clinical trials, researchers monitored thyroid risk via ultrasound or serum calcitonin, which "may have increased the number of unnecessary thyroid surgeries."
The Liraglutide Effect and Action in Diabetes (LEAD) trials also found more cases of pancreatitis among those on the drug than among controls, and the FDA urged cautious use of the drug in patients with a history of pancreatitis.
The five-year study will also monitor risk of pancreatitis, as well as hypoglycemia and allergic reactions.
Liraglutide was not associated with an increased risk of cardiovascular disease in the trials. However, Novo Nordisk will also have to conduct studies to provide more safety data as per new standards for cardiovascular safety data issued in the wake of controversy over the diabetes drug rosiglitazone (Avandia), which was shown to increase cardiovascular event risks.
In the LEAD trials, which included more than 3,900 patients, liraglutide significantly reduced hemoglobin A1c, with average reductions ranging from 1% to 1.5%, from baseline values of 8.2% to 8.6%.
The drug was also associated with weight loss in those trials.
There were no problems with hypoglycemia because the drug stimulates beta cells to release insulin only when blood glucose levels are high.
The most common adverse reactions included headache, nausea, diarrhea, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among patients on the drug than those on placebo.
Liraglutide is the second GLP-1 analogue approved by the FDA. Exenatide (Byetta) is given twice a day, although Eli Lilly and its marketing partners submitted a new drug application for a once-weekly version last year.
Novo Nordisk said it will introduce liraglutide to the U.S. market in four to six weeks. Last week, Japanese health officials also approved the drug.