Fifth Time’s a Charm?
By: Sylva Ohanian, Staff Writer
Liraglutide (Saxenda®) has recently been approved by the FDA for the treatment of chronic weight management in adult patients.1 The indication is specified for those with an initial body mass index (BMI) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related co-morbid condition, such as hypertension or type 2 diabetes.2
The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, which is indicated as an adjunct to increased physical activity and a reduced-calorie diet, has been available on the market as Victoza® since 2010 for the treatment of type 2 diabetes. While the dose for diabetes is 1.2 or 1.8 mg, the dose for obesity is 3 mg.3
As the fifth obesity drug that is now available in the United States, liraglutide invites comparisons with its predecessors. Currently, Trial 1807 is the only head-to-head trial that compares liraglutide to another weight loss drug. In a 20-week, double-blinded, placebo-controlled study, 564 obese individuals without type 2 diabetes, aged 18 to 65 years of age, were randomized to take one of the following: one of four liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3 mg) taken once daily, a placebo taken once daily, or orlistat 120 mg taken three times daily. Orlistat (Alli®, Xenical®) was initially approved in 1999.3 4 Orlistat is a reversible inhibitor of lipases and is indicated for obesity management including weight loss and weight maintenance when used in accordance with a reduced-calorie diet.4 After 20 weeks, patients had the option to enroll in an extension of the trial that lasted until a 52-week mark. As a result, “there was a significantly greater mean weight loss (in kg) in the groups treated with liraglutide 1.8, 2.4, and 3 mg compared with placebo (p < 0.001) at week 52. Treatment with liraglutide 2.4 and 3 mg was associated with a statistically significantly greater mean weight loss compared to orlistat (p < 0.05).” 5
Although liraglutide 2.4 and 3 mg proved superior in efficacy of weight loss to orlistat in phase 2 clinical trials for weight loss, other factors should be considered when deciding which drug is optimal. For instance, Saxenda® has a black box warning for thyroid c-cell tumors seen in rodent studies; it is not to be used in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2.2 Although orlistat does not have a black box warning, it has a warning about rare reports of severe liver injury that was discovered during routine monitoring of post-marketing adverse events.6 While orlistat’s infrequent hepatotoxic effect may still be alarming, it is important to note that post-marketing studies are still ongoing for Saxenda®.1
Along with the adverse effects of a drug, administration can seemingly influence a patient’s mind when looking at various options of any chronic condition’s management. Saxenda® comes as a subcutaneous injection that is administered once daily, while orlistat (Xenical®) is available orally but needs to be taken three times daily.2,4 Patient preference and adherence may be affected by the route and/or frequency of administration.
As medical advisors to patients, pharmacists must realize that it is pertinent to consider a drug’s many facets and remain unbiased when doing so. Until more information is available about Saxenda®, it is best to assess the risks and benefits of starting it as a treatment plan for individual patients.
- FDA approves weight-management drug Saxenda. U.S. Food and Drug Administration Website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm. Published December 23, 2014. Accessed January 05, 2015.
- Saxenda (liraglutide)[package insert]. Plainsboro, NJ: Novo Nordisk; Revised January 2015.
- Tucker ME. “FDA Approves Liraglutide (Saxenda) for Weight Loss.” Medscape Medical News. http://www.medscape.com/viewarticle/837147. Published December 23, 2014. Accessed January 05, 2015.
- Xenical (orlistat)[package insert]. South San Francisco, CA: Genentech, Inc; Revised December 2013.
- FDA Briefing Document. Liraglutide 3 mg (Saxenda). Endocrinologic and Metabolic Drugs Advisory Committee Meeting. U.S. Food and Drug Administration Website. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed January 06, 2015.
- Questions and Answers: Orlistat and Severe Liver Injury. U.S. Food and Drug Administration Website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213040.htm. Accessed January 06, 2015.