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The most common adverse events associated with liraglutide 3.0 mg, as compared with placebo, were primarily gastrointestinal, including nausea (39% vs. 14%), diarrhea (21% vs. 10%), constipation (19% vs. 9%) and vomiting (16% vs. 4%). Hypoglycemia was also more prevalent in patients taking liraglutide vs. placebo when used with a sulfonylurea (15% vs. 6%).
Serious adverse events that were more common in the liraglutide group vs. the placebo group included acute pancreatitis (7 participants vs. 1 participant) and acute gallstone disease (2.3% vs. 0.9%).
Researchers also evaluated cancer incidence, as risk for medullary thyroid cancer was a concern when liraglutide was approved as a diabetes treatment. The rate of thyroid neoplasms, however, was not significantly greater in patients taking liraglutide vs. placebo.
More breast neoplasms were noted in the liraglutide group, but this finding was not significant, according to the data.
Additionally, liraglutide was linked to a significant 2-bpm to 3-bpm increase in heart rate in an ongoing cardiovascular safety trial.
Weighing Benefits vs. Risks
In general, the advisory panel agreed that liraglutide 3.0 mg is effective for weight loss in overweight and obese patients and that the safety concerns do not loom large at the moment. Moreover, the drug may have some secondary health benefits as well, according to several committee members.
“The efficacy criteria met the current standard,” Barbara C. Hansen, PhD, of the Morsani College of Medicine at the University of Florida, said, noting that the drug could have a big effect on diabetes prevention. “I am also happy with the amount of risk that has been identified.”
Nevertheless, other panel members remained apprehensive.
“I don’t think we have enough information to mitigate the risks of malignancy,” said David Kelsen, MD, of Memorial Sloan Kettering Cancer Center in New York, who voted against recommending approval. Specifically, he pointed out that the higher incidence of cancer in the liraglutide group may not be linked to treatment with the drug, but without more data, firm conclusions cannot be made. “We need to look at the placebo control arms and demonstrate that there is simply a lead time bias [in detection of cancer].”
Although acting panel chair Kenneth D. Burman, MD, of the Washington Hospital Center in Washington, D.C., voted in favor of approval, he said he was “not completely assuaged” about the thyroid cancer risk and expressed some concern about the effects of the small increase in heart rate noted in patients treated with liraglutide.
“In general, I agree with the need for additional obesity agents that are useful,” he said. However, he noted that the studies were relatively short term and it is difficult to determine if a 5% to 7% weight loss is beneficial to hard outcomes. He also questioned “chronic use” of the drug for this indication.
“I’m especially concerned about chronic use of this medication in patients who are no longer losing weight or gaining some weight back. We need guidelines for long-term use and postmarketing studies definitely need to address side effects,” he added.
Despite these reservations, Dr. Burman conceded that the drug’s benefits outweigh the risks.
“Given the information we have at hand and taking into account all considerations, I recommend approval with the caveats noted,” he said.
Liraglutide 1.2 mg and 1.8 mg were approved under the brand name Victoza by the FDA in 2010 for treatment of type 2 diabetes.
Completion of the NDA review of liraglutide 3.0 mg (Saxenda) for weight management is expected by Oct. 20, 2014, according to a press release from Novo Nordisk.
The FDA is not required to follow the recommendations of its advisory committees, but it usually does.
