What is the comparative efficacy of liraglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist) vs semaglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

From the Guidelines

Semaglutide is generally more effective than liraglutide for weight loss, with clinical trials showing that semaglutide produces average weight loss of 15-17% of body weight after one year, compared to liraglutide which typically achieves 5-10% weight loss. The superior efficacy of semaglutide is likely due to its longer half-life and higher affinity for the GLP-1 receptor, allowing for weekly rather than daily dosing 1. Both medications work by mimicking the incretin hormone GLP-1, which increases insulin secretion, delays gastric emptying, reduces appetite, and increases satiety.

Key Differences Between Semaglutide and Liraglutide

• Semaglutide has a longer half-life, approximately one week, compared to liraglutide's 13 hours, allowing for weekly dosing 1
• Semaglutide has a higher affinity for the GLP-1 receptor, leading to greater efficacy in weight loss 1
• Clinical trials have shown that semaglutide produces greater weight loss, with a mean weight loss of 14.9% and 16.0% in the STEP 1 and STEP 3 trials, respectively, compared to liraglutide's mean weight loss of 8.0% in a clinical trial of 3731 individuals with obesity 1

Recommendations for Use

• Semaglutide should be started at a dose of 0.25 mg weekly, increasing monthly to the target dose of 2.4 mg, to minimize gastrointestinal side effects 1
• Liraglutide should be started at a dose of 0.6 mg daily, increasing weekly to 3 mg daily, to minimize gastrointestinal side effects 1
• Both medications should be used in conjunction with reduced calorie intake and increased physical activity for maximum effectiveness 1

Recent Evidence

A recent study published in 2024 found that semaglutide produced a significant reduction in weight after 68 weeks, with a mean weight change of −15.8%, compared to liraglutide's mean weight change of −6.4% 1. This study supports the use of semaglutide as a more effective treatment for weight loss compared to liraglutide.

From the Research

Comparative Efficacy of Liraglutide and Semaglutide for Weight Loss

• The comparative efficacy of liraglutide and semaglutide for weight loss has been evaluated in several studies 2, 3, 4, 5, 6.
• A systematic review and network meta-analysis found that semaglutide 2.4mg had the best weight loss effect, followed by liraglutide 3.0mg, semaglutide 1.0mg, and liraglutide 1.8mg 2.
• A retrospective observational cohort study found that both liraglutide and semaglutide were effective in reducing weight, with no significant difference between the two drugs, but semaglutide was more effective in reducing HbA1c levels 3.
• A randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial found that semaglutide was well tolerated and showed clinically relevant weight loss compared with placebo at all doses, with estimated mean weight loss ranging from -6.0% to -13.8% 4.
• A randomised, double-blind, phase 3a trial found that oral semaglutide was non-inferior to subcutaneous liraglutide in decreasing HbA1c and superior in decreasing bodyweight compared with both liraglutide and placebo at week 26 5.
• A randomised, open-label, 68-week, phase 3b trial found that once-weekly subcutaneous semaglutide resulted in significantly greater weight loss at 68 weeks compared with once-daily subcutaneous liraglutide, with a mean weight change from baseline of -15.8% vs -6.4% 6.

Safety and Tolerability

• The safety and tolerability of liraglutide and semaglutide have been evaluated in several studies 2, 3, 4, 5, 6.
• A systematic review and network meta-analysis found that the total incidence of adverse events was higher with semaglutide 2.4mg compared with liraglutide 3.0mg, liraglutide 1.8mg, and semaglutide 1.0mg 2.
• A retrospective observational cohort study found that both liraglutide and semaglutide were well tolerated, with no significant difference in adverse events between the two drugs 3.
• A randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial found that semaglutide was generally well tolerated, with no new safety concerns, and the most common adverse events were dose-related gastrointestinal symptoms 4.
• A randomised, double-blind, phase 3a trial found that oral semaglutide had a similar safety and tolerability profile to subcutaneous liraglutide 5.
• A randomised, open-label, 68-week, phase 3b trial found that gastrointestinal adverse events were reported by 84.1% of participants with semaglutide and 82.7% with liraglutide 6.