FDA Approves Liraglutide (Saxenda) for Weight Loss

Miriam E Tucker

December 23, 2014

The US Food and Drug Administration (FDA) has approved the diabetes drug liraglutide (Saxenda, Novo Nordisk) for the treatment of obesity.

The specific indication is as an adjunct to lifestyle for chronic weight management in individuals with a body mass index of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, diabetes, or dyslipidemia.

Available in the United States since 2010 for the treatment of type 2 diabetes as Victoza (Novo Nordisk), liraglutide is a glucagonlike peptide-1 (GLP-1) receptor agonist. The dose for obesity is 3.0 mg, in contrast to 1.2 mg or 1.8 mg for diabetes. Liraglutide should not be used with any other drug in the GLP-1 class, including Victoza, according to the FDA.

Patients should be evaluated after 16 weeks and the drug discontinued if the patient has not lost at least 4% of baseline body weight.

Liraglutide now becomes the fifth available obesity drug in the United States, after orlistat (Xenical, Genentech; and Alli, GlaxoSmithKline), lorcaserin (Belviq, Eisai), phentermine-topiramate (Qsymia, Vivus), and bupropion/naltrexone (Contrave, Takeda Pharmaceuticals).

The product will have a boxed warning stating that thyroid C-cell tumors have been seen in rodents but that the risk in humans is not known. Liraglutide should not be used in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2.

The approval also comes with the requirement for Novo Nordisk to conduct several postmarketing studies, including those in pediatric patients, an MTC registry of at least 15 years' duration, and an evaluation of potential breast cancer risk with liraglutide in ongoing clinical trials.

Novo Nordisk is also conducting the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) study, investigating the 1.8-mg dose for cardiovascular risk as well as for neoplasms and other adverse events. That study is scheduled to conclude in 2016.

The FDA approved liraglutide for weight loss under a risk evaluation and mitigation strategy consisting of a communication plan to inform healthcare providers about the serious risks of the drug.

Data Demonstrate Efficacy, Possible Thyroid Cancer Risk

Data supporting luraglutide’s efficacy and safety for obesity treatment come from four phase 3 trials conducted in more than 5000 patients, with more than 3000 receiving liraglutide 3.0 mg. Study completion was 70%.

In the largest trial (using the last observation carried forward), involving 3731 patients, the liraglutide group lost an average 8% of body weight vs 2.6% with placebo at 56 weeks, thereby meeting the FDA benchmark for weight-loss drugs of a 5% difference between active treatment and placebo.

Significantly more patients taking liraglutide lost 5% or more of their body weight vs placebo (63.5% vs 26.6%), and 32.8% and 10.1% patients, respectively, lost more than 10%. The FDA benchmark for losing 5% or more of body weight is 35% or greater.

In the trials, the most common adverse events with liraglutide 3.0 mg vs placebo were nausea (39% vs 14%), diarrhea (21% vs 10%), vomiting (16% vs 4%), and hypoglycemia when used in combination with sulfonylureas despite a halving of the sulfonylurea dose (15% vs 6%).

Serious adverse events included acute pancreatitis (seven patients with liraglutide vs one with placebo) and acute gallstone disease (2.3% vs 0.9%). Overall, the rate of neoplasms was not significantly greater with liraglutide 3.0 mg, but the incidence of thyroid neoplasm appeared to be above normal.

At an FDA advisory panel hearing held in September to review liraglutide's possible obesity indication, David W Cooke, MD, associate professor of pediatrics and clinical director of pediatric endocrinology at Johns Hopkins University, Baltimore, Maryland, said, "I thought the data very clearly supported efficacy in terms of weight loss, at least in a very large subset of patients taking it."

However, he added, "I'm less confident in the long-term health benefits, but I think since the safety data didn't raise any marked new concerns beyond what's already been considered for the marketed dosage, at this point I think it's reasonable to have it on the market as a weight-loss drug. [This will] allow the physician and patient to weigh those risks and benefits on an individual basis....Hopefully we'll get more data on the benefits as well as the safety in the postmarketing timeframe."


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