The Medical Letter on Drugs and Therapeutics
Liraglutide (Saxenda) for Weight Loss
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The injectable glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide, previously approved by the FDA for treatment of type 2 diabetes as Victoza,1 has now also been approved at a higher dose as Saxenda (Novo Nordisk) for chronic weight management in adults with a BMI ≥30, or a BMI ≥27 with a weight-related comorbidity such as hypertension, dyslipidemia, or diabetes.

DRUGS FOR WEIGHT LOSS – Pharmacologic treatment of obesity has been limited by modest efficacy, adverse effects, low adherence rates, and regain of weight with drug cessation.2 Drugs approved by the FDA for long-term treatment of obesity are listed in Table 2.

Phentermine/topiramate ER (Qsymia) is the most effective drug available to date for weight loss. Lorcaserin (Belviq) is only modestly effective, but is generally well tolerated.3 The lipase inhibitor orlistat (Xenical, Alli) is also modestly effective, but it can cause unpleasant adverse effects such as flatulence with discharge, oily spotting, and fecal urgency. The fixed-dose combination (Contrave) of bupropion (Wellbutrin SR, Zyban, and others) and naltrexone (ReVia, and others) has been effective, but nausea is common, and serious neuropsychiatric reactions have been reported.4

MECHANISM OF ACTION — Liraglutide decreases caloric intake. The exact mechanism is unknown; delayed gastric emptying and agonist effects on GLP-1 receptors in areas of the brain involved in appetite regulation have been implicated.

CLINICAL STUDIES – Table 1 summarizes the results of some randomized trials of liraglutide for weight loss in overweight or obese adults.

ADVERSE EFFECTS – Common adverse effects of liraglutide include nausea, diarrhea, constipation, vomiting, hypoglycemia, headache, decreased appetite, and dyspepsia. Acute pancreatitis and cholelithiasis, acute renal failure and worsening of chronic renal failure, increased heart rate, suicidal thoughts, and neuropsychiatric reactions have been reported in clinical trials. Serious hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients treated with liraglutide. Thyroid C-cell tumors have been reported in rodents given liraglutide, and the FDA has required a boxed warning about the risk of thyroid C-cell tumors in the package insert. The drug is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in those with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

PREGNANCY – Saxenda is contraindicated (category X) for use during pregnancy because weight loss is not beneficial for pregnant women and may harm the fetus.

 DRUG INTERACTIONS – Liraglutide delays gastric emptying and may decrease the rate of absorption of other drugs. For patients who are taking an insulin secretagogue concurrently, the dose of the insulin secretagogue should be reduced.

DOSAGE AND ADMINISTRATION – Saxenda is available in packages containing either three or five 18 mg/3 mL pre-filled multi-dose pens that deliver doses of 0.6, 1.2, 1.8, 2.4, or 3 mg. The starting dose for treatment of obesity is 0.6 mg injected subcutaneously in the abdomen, thigh, or upper arm once daily. The dose is titrated in weekly increments of 0.6 mg up to the recommended daily dosage of 3 mg once daily (the recommended daily dose for diabetes is 1.8 mg). If weight loss of ≥4% is not achieved within 16 weeks of starting treatment, liraglutide should be discontinued.

CONCLUSION – Use of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda) as an adjunct to diet and exercise resulted in placebo-corrected weight loss of about 6 kg after one year. As with other drugs approved for this indication, its effectiveness may wane in the second year and thereafter. Liraglutide must be injected daily, gastrointestinal adverse effects are common, and it is expensive.

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