A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Jatin Patel, Mercer University College of Pharmacy

Saxenda® (liraglutide (rDNA origin) injection) is considered a glucagon-like peptide-1 (GLP-1) receptor agonist. It is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes mellitus, or dyslipidemia).1

Saxenda® is not suggested for the treatment of type 2 diabetes and not indicated to be used in combination with any other GLP-1 receptors agonist and insulin. The recommended dose of Sexenda® is 3 mg subcutaneously in the abdomen, thigh or upper arm daily without regard to the timing of meals. Patients are instructed to initiate the medication at 0.6 mg per day for one week then increase the dose in weekly intervals until a dose of 3 mg is reached. 1

Title: A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Design Randomized, placebo-controlled trial
Objective To evaluate the efficacy and safety of 3.0 mg of liraglutide for weight management in overweight or obese adults who did not have diabetes at baseline
Study Groups Liraglutide group and placebo group
Methods The study conducted a 56-week, double-blind trial involving 3731, patients who did not have type 2 diabetes and who had a BMI (the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. Patients were randomly assigned in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide, starting at a dose of 0.6 mg with weekly 0.6 mg increments to 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. After 56 weeks, patients in the liraglutide group were randomly assigned in a 1:1 ratio to continue receiving liraglutide or switch to placebo for 12 weeks to assess efficacy and safety. Patients in the placebo group continued to receive placebo. Patients were evaluated every 2 weeks until week 8; thereafter, patients were evaluated every 4 weeks until week 44 and were evaluated again at weeks 50, 56, 58, 60, 64, 68, and 70.
Duration June 2011 through March 2013
Primary Outcome Measure The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight.
Baseline Characteristics Liraglutide (n=2487) Placebo (n=1244)
Sex – Female 78.7% 78.1%
Age – years 45.2±12.1 45.0±12.0
Race – White 84.7% 85.3%
Weight – kg 106.2±21.1 106.2±21.7
Body-mass index 38.3±6.4 38.3±6.3
Results End Point Liraglutide (n = 2437) Placebo (n = 1225) Estimated Treatment Difference, Liraglutide vs. Placebo (95% CI) p value
Coprimary end points        
Change in body weight        
·         % of body weight −8.0±6.7 −2.6±5.7 −5.4

(−5.8 to −5.0)

<0.001
·        Kilograms of body weight −8.4±7.3 −2.8±6.5 −5.6

(−6.0 to −5.1)

<0.001
Loss of ≥5% body weight 63.2% 27.1% 4.8

(4.1 to 5.6)

<0.001
Loss of >10% body weight 33.1% 10.6% 4.3

(3.5 to 5.3)

<0.001
Body weight-related end point        
·         Body-mass index −3.0±2.6 −1.0±2.3 −2.0

(−2.2 to −1.9)

<0.001
Adverse Events Common Adverse Events: nausea (40.2%), diarrhea (20.9%), constipation (20%), nasopharyngitis (17.2%), vomiting (16.3%), headache (13.2%), decreased appetite (10.8%), and dyspepsia (9.5%)
Serious Adverse Events: cholelithiasis (0.8%), cholecystitis acute (0.5%), osteoarthritis (0.2%), intervertebral disc protrusion (0.2%), pancreatitis acute (0.2%), cholecystitis (0.2%), breast cancer (0.2%), back pain (0.1%), uterine leiomyoma (<0.1%), and cellulitis (<0.1%)
Percentage that Discontinued due to Adverse Events: 9.9%
Study Author Conclusions In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control.

Liraglutide was associated with increased weight loss in overweight and obese adults who did not have diabetes. Patients did experienced modest improvements in fasting lipid levels, although the clinical relevance of these improvements is uncertain. In addition, patient had greater reductions in fasting and postprandial glycemic variables and improvements in insulin sensitivity than placebo group. Even though the study included the use of last-observation-carried-forward imputation in the pre-specified primary analyses, patients who withdrew from the trail were accounted with the use of alternative imputation methods. On the other hand, no correction for multiple testing was performed for secondary end points.

References

  1. Saxenda® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; Revised December 2014.
  2. Pi-sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22.
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