SAXENDA® (LIRAGLUTIDE)





Acronyms


DRUGS IN CLASS


MECHANISM OF ACTION


FDA-APPROVED INDICATIONS


WEIGHT LOSS


RCT
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. (
RCT
SCALE prediabetic extension study - Liraglutide vs Placebo for New-onset Diabetes in Overweight Prediabetic Adults, Lancet (2017) [PubMed abstract]
  • This substudy of the SCALE study took patients who were prediabetic at enrollment (N=2254 | liraglutide - 1505, placebo 749) and treated them for an additional 104 weeks (160 weeks total). The substudy's primary outcome 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.
RCT
STEP 8 trial - Wegovy vs Saxenda for Weight Loss in Overweight Adults, JAMA (2022) [PubMed abstract]
  • The STEP 8 trial enrolled 338 adults with BMI ≥ 30 or ≥ 27 and 1 or more weight-related comorbidities
Main inclusion criteria
  • Adults ≥ 18 years
  • BMI ≥ 30 or ≥ 27 with one weight-related condition (OSA, hyperlipidemia, CVD, hypertension)
  • ≥ 1 self-reported unsuccessful dietary weight loss effort
Main exclusion criteria
  • Diabetes
  • HgA1C ≥ 6.5%
  • Weight change ≥ 5 kg in last 90 days
Baseline characteristics
  • Average age 49 years
  • Female sex - 78.4%
  • Average BMI - 38
  • Average weight - 231 lbs (105 kg)
Randomized treatment groups
  • Group 1 (126 patients): Wegovy (semaglutide) 2.4 mg once weekly
  • Group 2 (127 patients): Saxenda (liraglutide) 3 mg once daily
  • Group 3 (85 patients): Placebo
  • Patients were randomized 3:1 to Wegovy or matching placebo or 3:1 to Saxenda or matching placebo. Wegovy and Saxenda treatment group assignments were not blinded.
  • Wegovy was titrated to 2.4 mg over 16 weeks. A 1.7 mg maintenance dose was permitted if 2.4 mg could not be tolerated
  • Saxenda was titrated over 4 weeks. If 3.0 mg dose was not tolerated, treatment could be restarted, with reescalation over 4 weeks.
Primary outcome: Percentage change from baseline in body weight at week 68
Results

Duration: 68 weeks
Outcome Wegovy Saxenda Comparisons
Primary outcome (% weight loss) 15.8% 6.4% p<0.001
People with ≥ 10% weight loss 71% 26% p<0.001
People with ≥ 20% weight loss 39% 6% p<0.001
Actual weight loss 34 lbs (15.3 kg) 15 lbs (6.8 kg) diff 8.5, 95%CI[11.2 to 5.7]
Discontinued treatment 13.5% 27.6% N/A
Nausea 61% 59% N/A
Constipation 39% 32% N/A
Diarrhea 28% 18% N/A
Vomiting 25% 21% N/A
  • Weight loss for the pooled placebo groups was 1.9%
  • Among subjects who did not stop treatment, 86.2% received the 2.4-mg dose of semaglutide and 95.7% received the 3.0-mg dose of liraglutide

Findings: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.


WEIGHT LOSS IN CHILDREN


RCT
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.

RCT
SCALE Kids - Liraglutide vs Placebo in Children 6 to <12 Years with Obesity, NEJM (2025) [PubMed abstract]
  • SCALE Kids enrolled 82 children aged 6 to <12 years old with obesity
Main inclusion criteria
  • Age 6 to <12 years
  • Age- and sex-adjusted BMI ≥ 95th percentile
  • History of failed weight loss
  • Pubertal Tanner stage 1 through 5
Main exclusion criteria
  • Type 1 diabetes
  • Secondary causes of obesity
  • History of depression
  • Significant psychiatric disorder
Baseline characteristics
  • Average age 10 years
  • Male - 54%
  • BMI ≥95% to <120% - 24%
  • BMI ≥120% to <140% - 37%
  • BMI ≥140% - 39%
  • Mean BMI - 31
  • Mean % of 95th percentile - 137%
  • Mean weight - 70 kg (154 lbs)
  • Insulin resistance - 20%
  • Impaired glucose tolerance - 12%
  • Type 2 diabetes - 0%
  • Average HgA1C - 5.4%
Randomized treatment groups (2:1)
  • Group 1 (56 patients): Liraglutide with a target of 3 mg subcutaneously once daily
  • Group 2 (26 patients): Placebo
  • All participants received lifestyle interventions consisting of individualized diet and exercise counseling
  • Liraglutide was initiated at a dose of 0.6 mg/day for 1 week for participants with a body weight at randomization of at least 45 kg (99 lbs) (0.3 mg/day for 1 week for those with a body weight at randomization of <45 kg (99 lbs)). Dosing was increased in increments of 0.6 mg per week over a maximum of 8 weeks (for participants with a body weight of ≥ 45 kg (99 lbs)) or 10 weeks (for those with a body weight <45 kg (99 lbs) until a once-daily dose of 3.0 mg or the maximum tolerated dose was reached.
Primary outcome: The percentage change in the body mass index (BMI)
Results

Duration: 56 weeks
Outcome Liraglutide Placebo Comparisons
Primary outcome (% change in BMI) -5.8% 1.6% p<0.001
Percent increase in body weight 1.6% 10.0% p=0.001
BMI reduction of ≥ 5% 46% 9% p=0.02
Increase in body weight 1.1 kg (2.4 lbs) 7.1 kg (16 lbs) diff −6.0 kg 95%CI [−9.3 to −2.7]
Discontinue drug due to side effects 11% 0% N/A
  • In the liraglutide group, 89% of participants reached the maximum dose of 3 mg/day
  • The most common adverse events in the liraglutide group were nausea, vomiting, and diarrhea. Three cases of vomiting were considered to be serious; however, none required hospitalization, and all resolved without sequelae. Gastrointestinal events were managed with antiemetic agents, antinausea medications, PPIs, and liraglutide dose reduction or interruption.

Findings: Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions.


SIDE EFFECTS


  • 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%














CONTRAINDICATIONS


PRECAUTIONS






DRUG INTERACTIONS



DOSING



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

LONG-TERM SAFETY


BIBLIOGRAPHY