Liraglutide vs semaglutide
Liraglutide and semaglutide are both acylated GLP-1 receptor agonists with FDA labels, differing in sequence homology to human GLP-1, dosing interval and half-life. 1,2 A randomized head-to-head trial (STEP 8) compared once-weekly semaglutide 2.4 mg with once-daily liraglutide 3.0 mg for weight management in adults without diabetes. 3
Side by side
| Field | Liraglutide | Semaglutide |
|---|---|---|
| Class | GLP-1 receptor agonist 1 | GLP-1 receptor agonist 2 |
| Mechanism / receptors | Acylated human GLP-1 receptor agonist with 97% sequence homology to endogenous GLP-1(7-37). 1 | Selective GLP-1 receptor agonist described as a GLP-1 analogue with 94% sequence homology to human GLP-1. 2 |
| Origin | Acylated GLP-1 analogue, stable against DPP-4 and neutral endopeptidase degradation. 1 | Modified GLP-1 analogue with a C18 fatty di-acid and DPP-4 stabilization at position 8. 2 |
| Half-life | Plasma half-life of approximately 13 hours; the label ties this to once-daily use. 1 | Approximately 1 week (per label). 2 |
| Highest trial phase | Approved; phase 3 (SCALE) 4 | Approved; phase 3 (STEP) 5 |
| FDA status | Saxenda: chronic weight management in adults and in pediatric patients 12 years and older with body weight above 60 kg and obesity. Victoza: type 2 diabetes in adults and pediatric patients 10 years and older, and cardiovascular-event risk reduction in adults with type 2 diabetes and established CV disease. 1,6 | Wegovy: cardiovascular-event risk reduction, chronic weight management in adults and in patients 12 years and older with obesity, and noncirrhotic MASH. 2 |
| Published outcomes (weight) | SCALE (56 weeks, no type 2 diabetes): mean loss 8.4 kg vs 2.8 kg with placebo. 4 | STEP 1 (68 weeks, no diabetes): mean change -14.9% vs -2.4% with placebo. 5 |
| Head-to-head (STEP 8) | Liraglutide 3.0 mg daily: mean change -6.4% at week 68. 3 | Semaglutide 2.4 mg weekly: mean change -15.8% at week 68 (difference vs liraglutide -9.4 percentage points). 3 |
| Safety signals | Boxed warning for thyroid C-cell tumors in rats and mice; common adverse reactions include nausea, diarrhea, constipation and vomiting. 1 | Boxed warning for thyroid C-cell tumors in rodents; pancreatitis and gallbladder warnings. 2 |
| Evidence level | Regulatory and randomized phase 3 human evidence 1,4 | Regulatory and randomized phase 3 human evidence 2,5 |
Liraglutide: what the data says
SCALE randomized 3,731 adults without type 2 diabetes who had obesity, or overweight with dyslipidemia or hypertension, 2:1 to liraglutide 3.0 mg once daily or placebo for 56 weeks. 4 Mean weight loss was 8.4 kg with liraglutide and 2.8 kg with placebo; 63.2% versus 27.1% lost at least 5% of body weight. 4 Serious events occurred in 6.2% of the liraglutide group and 5.0% of the placebo group. 4
The Saxenda label's pooled table reports nausea in 39.3% versus 13.8% with placebo, diarrhea in 20.9% versus 9.9%, and vomiting in 15.7% versus 3.9%. 1 The Victoza label describes liraglutide's use in type 2 diabetes and lists a boxed warning for thyroid C-cell tumors. 6
Semaglutide: what the data says
STEP 1 randomized 1,961 adults with obesity or overweight and without diabetes 2:1 to semaglutide 2.4 mg weekly or placebo for 68 weeks; mean weight change was -14.9% versus -2.4%. 5 The Wegovy label's pooled table reports nausea in 44% versus 16% with placebo, diarrhea in 30% versus 16%, and vomiting in 24% versus 6%. 2
STEP 8 randomized 338 adults in an open-label comparison of semaglutide 2.4 mg weekly versus liraglutide 3.0 mg daily, each with matched placebo, over 68 weeks. 3 Weight reductions of at least 10%, 15% and 20% were reported for 70.9%, 55.6% and 38.5% of the semaglutide group versus 25.6%, 12.0% and 6.0% of the liraglutide group. 3
Key research differences
- Dosing interval and half-life differ: the liraglutide label describes a plasma half-life of about 13 hours consistent with once-daily use, while the semaglutide label describes a half-life of about 1 week. 1,2
- In STEP 8 (338 adults without diabetes, 68 weeks, open-label), mean weight change was -15.8% with semaglutide and -6.4% with liraglutide, versus -1.9% with pooled placebo. 3
- Discontinuation for any reason in STEP 8 was 13.5% with semaglutide and 27.6% with liraglutide, while gastrointestinal adverse events were reported by 84.1% and 82.7%, respectively. 3
- Labeled uses differ: liraglutide is marketed as Saxenda for weight management and as Victoza for type 2 diabetes, whereas the semaglutide weight-management label (Wegovy) also lists cardiovascular-event risk reduction and MASH. 1,2,6
- Sequence homology to human GLP-1 is described as 97% for liraglutide (relative to GLP-1(7-37)) and 94% for semaglutide. 1,2
Where the evidence is limited
STEP 8 was open-label for the semaglutide-versus-liraglutide comparison and enrolled adults without diabetes, so its findings do not directly describe other populations or the type 2 diabetes setting. 3 Cross-label adverse-reaction percentages come from different trial pools and the labels warn they cannot be directly compared. 1,2 Head-to-head data in type 2 diabetes were not part of the sources reviewed here. 6
Frequently asked questions
Have liraglutide and semaglutide been compared directly for weight management?
Do both carry a boxed warning?
How long does each molecule persist in the body according to its label?
References
- SAXENDA (liraglutide) injection, prescribing information FDA label (DailyMed). 2026
- WEGOVY (semaglutide) injection, prescribing information FDA label (DailyMed). 2026
- Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial JAMA. 2022
- A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity and Prediabetes) N Engl J Med. 2015
- Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) N Engl J Med. 2021
- VICTOZA (liraglutide) injection, prescribing information FDA label (DailyMed). 2025
For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.