One-year results detailing the use of liraglutide (Saxenda, Novo Nordisk) for the treatment of obesity in the Satiety and Clinical Adiposity—Liraglutide (SCALE) study have now been published, while unpublished extension trial data suggest continued efficacy and safety at 3 years, as well as prevention of type 2 diabetes.
One of the authors of an accompanying editorial says the SCALE publication will inspire more confidence among doctors to use this agent for obesity, but its high cost remains a significant hurdle to adoption. Liraglutide for obesity costs around $1000 a month in the United States and is not currently widely reimbursed.
Findings for the 56-week SCALE study were published online July 1, 2015 in the New England Journal of Medicine by Xavier Pi-Sunyer, MD, professor of medicine at Columbia University College of Physicians and Surgeons and director of the New York Obesity Research Center, New York, and colleagues.
As Dr Pi-Sunyer previously reported at the 2014 American Association of Clinical Endocrinologists meeting and Novo Nordisk officials presented to a Food and Drug Administration advisory panel in September 2014, liraglutide, an injectable glucagonlike peptide-1 receptor (GLP-1) agonist, combined with diet and exercise, was associated with a significant 5.6-kg greater weight loss and improvement in some cardiometabolic risk factors compared with placebo at 56 weeks. Two-thirds of patients on liraglutide lost at least 5% of their body weight, compared with just over a quarter of those on placebo.
Based on those data among others, the FDA approved liraglutide for use in obesity at a 3.0-mg/day dose — in contrast to the 1.8-mg dose for type 2 diabetes that it was already approved for — in the United States in December 2014. The European Medicines Agency followed suit in January 2015, as did Canada in February 2015.
"This article describes the use of liraglutide for weight loss in overweight and obese adults without diabetes. It shows that weight loss is achieved that can retard the progression of prediabetic persons to frank diabetes, it can improve cardiovascular risk factors, and it can enhance quality of life," Dr Pi-Sunyer told Medscape Medical News.
Publication Includes Supplemental Data Previously Unseen
Elias S Siraj, MD, professor of medicine and director of the diabetes program at Temple University School of Medicine and Hospital, in Philadelphia, Pennsylvania, told Medscape Medical News that the publication of the data — including supplemental information not previously released — inspires more confidence about using the drug for obesity, at least from a medical standpoint.
"We were waiting for the official publication, [which]…with the supplemental information I think will lead to more use for this indication. It's there for people to look at," noted Dr Siraj, who penned an editorial accompanying the study results in collaboration with Kevin Jon Williams, MD, of Temple University and the University of Gothenburg in Sweden.
Specifically, Dr Siraj said, the published data support use of liraglutide in people who are obese (body mass index [BMI] greater than 30 kg/m2) or in those who are overweight (BMI 27–30 kg/m2) and who have comorbidities including diabetes, hypertension, and dyslipidemia. (The study didn't include people with diabetes at baseline, but the FDA approval for Saxenda does.)
"The more of those problems they have, the more likely they are to benefit," he told Medscape Medical News.
He added, "Previous studies have shown that as little as 5% weight loss leads to improvement in obesity-related complications....It's not huge from a cosmetic perspective. The person might not even look different, but it does make a difference in terms of metabolic parameters and complications."
Nonetheless, in the editorial he and Dr Williams point out, "Liraglutide is no cure. Most obese patients stayed obese, reversal of metabolic syndrome was not quantified, and liraglutide may be required indefinitely, like statins, but with delivery by injection and at a nontrivial cost."
The cost for Saxenda — $1068 for a 1-month supply — is consistent with the per-mg price of liraglutide's diabetes formulation (Victoza). While Saxenda is not widely reimbursed by public or private insurers, Novo Nordisk has a cost-assistance program, and some patients have gained access to it through a variety of plans and payers.
This is an indication that payers are recognizing the need to include therapeutic options as part of the treatment plan for patients struggling with obesity and chronic weight management, a company spokesperson told Medscape Medical News. Novo Nordisk remains committed to securing coverage and making access feasible for patients and as such is in discussions with payers, the spokesperson added.
Extension Trial Data Suggest Further Benefit
Novo Nordisk announced results from the 3-year extension trial in May. With about half of the original SCALE cohort completing the full 160 weeks of this, those in the liraglutide group maintained an average body weight loss of 6.1% from baseline, compared with 1.8% for placebo, a significant difference (P < .0001.
The risk for developing type 2 diabetes was reduced by approximately 80% with liraglutide (P < .0001), and the time to onset for those who did develop it was approximately 2.6 times longer.
Withdrawals due to adverse events were 12.7% with liraglutide vs 5.7% with placebo, most of them gastrointestinal.
Asked to comment on the extension trial, Dr Siraj told Medscape Medical News, "The results have not been published and peer-reviewed yet; therefore we have to be careful in interpreting the limited data that have been released by the company. Having said that, the data seem to show continuing benefit close to 3 years in patients who were on liraglutide, even though there was slightly less weight loss compared with after 1 year."
The original SCALE trial was conducted between June 2011 and March 2013 at 191 sites in 27 countries in Europe, North America, South America, Asia, Africa, and Australia. Subjects were 18 years of age or older and had BMIs of 30 kg/m2 or greater or 27 kg/m2 or greater with treated or untreated dyslipidemia or hypertension. None had diabetes at baseline.
A total 3731 patients were randomized to 3.0-mg/day liraglutide or placebo. Of those, 72% of the liraglutide group and 64% of placebo subjects completed the 56 weeks. More of the liraglutide group withdrew due to adverse events, 10% vs 4%.
After 56 weeks, the liraglutide group had lost an average of 8.0 kg, compared with 2.8 kg with placebo. The proportion losing at least 5% of their body weight was 63%, vs 27% in the placebo group, while 33% vs 11% lost more than 10%. Overall, approximately 92% lost weight on liraglutide, compared with 65% on placebo.
The liraglutide group also had greater reductions in HbA1c, plasma glucose, systolic and diastolic blood pressure, and improvement in all measures of fasting lipids along with other metabolic parameters. They also scored higher on scales for overall physical and mental health.
Signals for Pancreatitis, Breast Cancer, but Numbers Small
Safety analyses included 2481 liraglutide and 1242 placebo subjects. Gastrointestinal events were more common with liraglutide than with placebo, including nausea in 40% vs 15%, diarrhea in 21% vs 9%, and vomiting in 16% vs 4%. Most were mild to moderate in severity and occurred primarily within the first 4 to 8 weeks of treatment, Dr Pi-Sunyer and colleagues report.
Gallbladder-related events were more common in the liraglutide group, 2.5% vs 1.0% with placebo. This finding is consistent with the known relationship between weight loss and gallstones, the authors note.
There was also a numeric increase in pancreatitis cases in the liraglutide group, 0.4% vs less than 0.1% with placebo (10 patients vs 1). Nine of these cases were mild, and in five of the liraglutide patients the pancreatitis was related to gallstones. There have been concerns about pancreatitis with incretin drugs, including GLP-1 agonists.
A numeric imbalance also was seen in the incidence of malignant and premalignant breast neoplasms: 10 in 9 women in the liraglutide group vs 3 in 3 female placebo subjects. The authors suggest that perhaps these women were being checked more carefully for cancers by their primary-care providers, since they were losing weight.
Dr Siraj told Medscape Medical News that those numbers are simply too small to draw any conclusions. "Long-term observations will be needed to address that."
No new safety issues arose during the extension trial, according to Novo Nordisk.
In the meantime, Dr Siraj said, "Cost is a major issue. I do hope insurers will consider loosening their criteria to cover these agents."
SCALE was funded by Novo Nordisk. Dr Pi-Sunyer reports receiving fees for serving on advisory boards from Novo Nordisk, Eli Lilly, Weight Watchers, and Johnson & Johnson. Disclosures for the coauthors are listed on the journal website. Dr Siraj is a consultant for Corcept Therapeutics on a drug for Cushing's syndrome.
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Cite this: Publication Boosts Liraglutide for Obesity, but Cost an Issue - Medscape - Jul 01, 2015.