STEPS

New Drug Reviews

Liraglutide (Saxenda) for Weight Loss

J. SUZIN WHITTEN, MD, Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, Massachusetts

STEPS new drug reviews Liraglutide (Saxenda) is a glucagon-like peptide-1 (GLP-1) receptor agonist that, in addition
cover Safety, Tolerability, to stimulating insulin release and inhibiting glucagon secretion, slows gastric emptying and
Effectiveness, Price, and
Simplicity. Each indepen- increases satiety after eating. It is labeled as an adjunct to diet and exercise for weight manage-
dent review is provided ment in overweight or obese adults. It is a higher-dose version of the same product used to
by authors who have no treat type 2 diabetes mellitus.
financial association with
the drug manufacturer.
This series is coordinated Drug Dosage Dose form Cost*
by Allen F. Shaughnessy,
PharmD, MMedEd, Con- Liraglutide 0.6 mg once daily for one Prefilled, multidose pen for Approximately
tributing Editor. (Saxenda) week, increasing by 0.6 mg subcutaneous injection containing $1,194
A collection of STEPS pub- weekly to target dosage of 0.6-mg, 1.2-mg, 1.8-mg, 2.4-mg,
lished in AFP is available 3 mg once daily or 3-mg dose
at http://www.aafp.org/
afp/steps. *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com
(accessed June 2, 2016).

SAFETY thyroid cancers as well as multiple endocrine

Safety concerns with liraglutide include acute neoplasia syndrome type 2 because of reports
gallbladder disease, acute pancreatitis, and of thyroid tumors in animals.1 As with other
risk of severe hypoglycemia.1-3 Gallbladder GLP-1 receptor agonists, transient pulse ele-
disease and cholecystitis can occur in patients vations of uncertain clinical significance have
rapidly losing weight by any means, but the been reported, with return to baseline after
rates are higher in patients using liraglutide cessation of liraglutide therapy.1-3 Long-term
(number needed to harm [NNH] = 100 safety (greater than two years) has not been
and 250, respectively) and rise with increas- studied.
ing weight loss.1,2 The risk of pancreatitis is Liraglutide is a U.S. Food and Drug
relatively low (0.3%), but transient elevations Administration pregnancy category X drug.
of pancreatic enzymes of uncertain clinical Because it is unknown if the medication
significance can occur.1-3 Although sulfo- is excreted in breast milk, it should not be
nylureas and other insulin secretagogues are taken by breastfeeding women. Liraglutide is
not contraindicated for use with liraglutide, not approved for use in children.
their dose should be lowered by at least 50%
TOLERABILITY
if they are continued while patients are taking
liraglutide. Both severe (NNH = 143) and Gastrointestinal symptoms are common,
symptomatic (NNH = 10) hypoglycemia have and approximately 10% of patients will stop
occurred in patients with type 2 diabetes who treatment because of adverse effects.2-4 Nau-
are taking sulfonylureas and liraglutide for sea (39%), diarrhea or constipation (20%),
weight loss.1,2 Liraglutide should not be used and vomiting (15%) are reported with lira-
in patients taking insulin.1,2 Kidney injury glutide. About one in four patients with
may occur in volume-depleted patients.1 type 2 diabetes will experience symptomatic
Liraglutide is contraindicated in patients with hypoglycemia at least once over the course of
a family or personal history of medullary one year.1-4
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STEPS

EFFECTIVENESS until the target dosage of 3 mg per day is

Liraglutide has been evaluated in two double- reached. Patients who are unable to toler-
blind studies of more than 3,000 obese or ate the 3-mg dose should stop treatment, as
overweight patients with hyperlipidemia, should patients who do not lose 4% of their
hypertension, or diabetes. In both studies, baseline body weight after four months. If
adding liraglutide to lifestyle counseling for patients achieve clinically significant weight
one year resulted in an average 8.9- to 13.3-lb loss after one year, liraglutide may be contin-
(4- to 6-kg) greater weight loss.2-4 A clini- ued to maintain weight loss. Syringes should
cally significant weight loss of 5% of baseline be refrigerated until first use, but then may
body weight at one year was also consistently be refrigerated or kept at room temperature
achieved by more than one-half of patients for up to 30 days.1
treated with liraglutide (number needed to
treat [NNT] = 2 to 3).2,3 A 10% loss (approxi- Bottom Line
mately 22 lb [10 kg]) was achieved in 25% to Liraglutide, combined with lifestyle counsel-
33% of patients (NNT = 4 to 5).2,3 Sustained ing, produces a clinically significant and sus-
weight loss for up to two years has been tained weight loss that continues as long as it
demonstrated with continued use of liraglu- is used. Nausea and vomiting, however, are
tide, but weight gain may occur with discon- common adverse effects, and about one in
tinuation of the drug.2,5 Liraglutide has been 10 patients will discontinue treatment. Lira-
shown to be superior to orlistat (Xenical) for glutide has not been studied to determine its
achieving clinically significant weight loss at effect on patient-oriented outcomes such as
one and two years of use.5 the development of osteoarthritis, preven-
Liraglutide improves cardiometabolic tion of cardiovascular disease, and reduction
markers such as blood pressure, waist cir- of mortality.
cumference, body mass index, and A1C,
Address correspondence to J. Suzin Whitten, MD, at
although the clinical relevance of these jwhitten@challiance.org. Reprints are not available
reductions remains uncertain.2,3 Patients from the author.
may also report improved physical function, Author disclosure: No relevant financial affiliations.
as measured by a validated self-reported
measure of obesity-related quality of life.2,3 REFERENCES
As with other pharmacologic treatments,
1. Daily Med. Drug label information: Saxenda (liraglu-
liraglutide has not been studied to determine tide injection, solution). https://dailymed.nlm.nih.gov/
its effect on cardiovascular- or diabetes- dailymed/drugInfo.cfm?setid=3946d389-0926-4f77-
related morbidity, or overall mortality. It a708-0acb8153b143. Accessed January 8, 2016.
has not been studied when used in conjunc- 2. Davies MJ, Bergenstal R, Bode B, et al.; NN8022-
1922 Study Group. Efficacy of liraglutide for weight
tion with other obesity treatments. loss among patients with type 2 diabetes: the SCALE
diabetes randomized clinical trial [published correc-
PRICE tion appears in JAMA. 2016;315(1):90]. JAMA. 2015;​
314(7):687-699.
A one-month supply of liraglutide at the
3. Pi-Sunyer X, Astrup A, Fujioka K, et al.; SCALE Obe-
target dosage of 3 mg per day costs approxi- sity and Prediabetes NN8022-1839 Study Group. A
mately $1,194. In comparison, orlistat costs randomized, controlled trial of 3.0 mg of liraglutide in
$580 for 120 mg three times per day for 30 weight management. N Engl J Med. 2015;373(1):11-22.
days and zonisamide (Zonegran) costs $30 4. Lean ME, Carraro R, Finer N, et al.; NN8022-1807
Investigators. Tolerability of nausea and vomiting and
($400) for 100 mg per day for 30 days. associations with weight loss in a randomized trial of
liraglutide in obese, non-diabetic adults. Int J Obes
SIMPLICITY (Lond). 2014;38(5):689-697.

The starting dosage of liraglutide is 0.6 mg 5. Astrup A, Carraro R, Finer N, et al.; NN8022-1807 Inves-
tigators. Safety, tolerability and sustained weight loss
daily, injected subcutaneously at any time over 2 years with the once-daily human GLP-1 analog,
of day without regard to meals. The dos- liraglutide. Int J Obes (Lond). 2012;36(6):843-854. ■
age should be increased weekly by 0.6 mg

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