SAXENDA® (LIRAGLUTIDE)



















SCALE Study - Liraglutide vs Placebo for Weight Loss in Overweight Nondiabetic Adults, NEJM (2015) [PubMed abstract]
  • The SCALE study enrolled 3731 overweight adults who did not have diabetes
Main inclusion criteria
  • BMI ≥ 30; or ≥ 27 with dyslipidemia and/or hypertension
  • < 5 kg change in body weight in previous 3 months
  • History of failed dieting
Main exclusion criteria
  • Type 1 or 2 diabetes
  • Use of medications that cause weight gain or loss
  • Previous GLP-1 analog therapy
  • Previous bariatric surgery
  • History of pancreatitis
  • History of significant psychiatric disorder
Baseline characteristics
  • Average age 45 years
  • Female sex - 78%
  • Average weight - 233 lbs (106 kg)
  • Average BMI - 38
Randomized treatment groups (2:1 ratio)
  • Group 1 (2487 patients): Liraglutide 3 mg once daily
  • Group 2 (1244 patients): Placebo
  • Liraglutide was started at 0.6 mg once daily and increased in 0.6 mg increments at weekly intervals to 3 mg
  • All patients received counseling on lifestyle modification
Primary outcome: The three prespecified coprimary endpoints, assessed at week 56, were weight change from baseline, the proportion of patients who lost at least 5% of their baseline body weight, and the proportion of patients who lost more than 10% of their baseline body weight
Results

Duration: 56 weeks
Outcome Liraglutide Placebo Comparisons
Weight loss 18.5 lbs (8.4 kg) 6.2 lbs (2.8 kg) p<0.001
% weight loss 8% 2.6% p<0.001
Loss ≥ 5% body weight 63.2% 27.1% p<0.001
Loss > 10% body weight 33.1% 10.6% p<0.001
Nausea 40.2% 14.7% N/A
Diarrhea 20.9% 9.3% N/A
Constipation 20% 8.7% N/A
Vomiting 16.3% 4.1% N/A
Dropouts 28.1% 35.6% N/A

Findings: 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. (

SCALE prediabetic extension study - Liraglutide vs Placebo for New-onset Diabetes in Overweight Prediabetic Adults, Lancet (2017) [PubMed abstract]
  • This study is a substudy of the SCALE study. Patients who were prediabetics at enrollment to the SCALE study were treated for an additional 104 weeks (160 weeks total). The primary outcome of the extension study was average time to diabetes onset.


Duration: 160 weeks
Outcome Liraglutide Placebo Comparisons
New-onset diabetes 2% 6% N/A
Average time to diabetes onset 99 weeks 87 weeks p<0.0001
Weight loss 14.3 lbs (6.5 kg) 4.4 lbs (2 kg) p<0.0001
% weight loss 6.1% 1.9% p<0.0001
Loss ≥ 5% body weight 49.6% 23.7% p<0.0001
Loss > 10% body weight 24.8% 9.9% p<0.0001
Dropouts 47% 55% N/A

Findings: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3.0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes.





Saxenda vs Placebo for Weight Loss in Obese Adolescents, NEJM (2020) [PubMed abstract]
  • The trial enrolled 251 obese adolescents aged 12 - 17 years
Main inclusion criteria
  • 12 - 17 years old
  • BMI ≥ 30
  • No weight change ≥ 11 lbs within 90 days
  • Poor response to lifestyle therapy
Main exclusion criteria
  • Pre-pubertal
  • Body weight ≤ 132 lbs (60 kg)
  • Type 1 diabetes
Baseline characteristics
  • Average age 14.5 years
  • Female sex - 75%
  • Average body weight - 222 lbs (101 kg)
  • Average BMI - 35
  • Diabetes or prediabetes - 26%
Randomized treatment groups
  • Group 1 (125 patients): Liraglutide 3 mg subcutaneously once daily for 56 weeks
  • Group 2 (126 patients): Placebo
  • Dosing was started at 0.6 mg/day and titrated on a weekly basis to 3 mg/day (82% of patients in the liraglutide group achieved 3 mg/day)
  • There was a 12-week run-in period where all participants received lifestyle therapy
  • At the end of the 56 week treatment period, there was a 26-week follow-up period without treatment
Primary outcome: Change from baseline in the BMI standard-deviation score at week 56. The BMI standard-deviation score is a measure of the number of standard deviations from the population mean BMI, matched for age and sex
Results

Duration: 56 weeks
Outcome Liraglutide Placebo Comparisons
Primary outcome -0.23 0 difference −0.22 (−0.37 to −0.08)
BMI (absolute change) -1.39 +0.19 difference −1.58 (−2.47 to −0.69)
Body weight -4.97 lbs (2.26 kg) +4.95 lbs (2.25 kgs) difference −9.9 (−15.7 to −4.0)
Nausea 42.4% 14.3% p<0.001
Vomiting 34.4% 4% p<0.001
Gastroenteritis 12.8% 4.8% p=0.02
Dizziness 10.4% 3.2% p=0.02
Dropout rate 19.2% 20.6% N/A
  • During the 26-week drug-free follow-up period, the liraglutide group gained back the weight they loss plus an additional 3.7 lbs (1.7 kg) on average

Findings: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy.





  • Reference [1]
Side effect Saxenda Placebo
Nausea 39% 14%
Diarrhea 21% 10%
Constipation 19.4% 8.5%
Vomiting 15.7% 3.9%
Upset stomach 9.6% 2.7%
Abdominal pain 5.4% 3.1%
GERD 4.7% 1.7%
Burping 4.5% 0.2%
Flatulence 4% 2.5%































Saxenda titration schedule for adults and children ≥ 12 years old
Week Saxenda dose
1 0.6 mg once daily
2 1.2 mg once daily
3 1.8 mg once daily
4 2.4 mg once daily
5 and on 3 mg once daily
  • Dose is titrated to limit GI side effects
  • Consider delaying escalation for 1 week if patient cannot tolerate increase
  • Pediatric patients may lower dose to previous level if needed