What is the role of GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Saxenda) (liraglutide) and semaglutide (Wegovy) (semaglutide), in weight loss?

From the Guidelines

GLP-1 receptor agonists, such as semaglutide (Wegovy) and liraglutide (Saxenda), are effective medications for weight loss in adults with obesity, with semaglutide demonstrating a mean weight loss of 14.9-16.0% over 68 weeks, compared to 2.4-5.7% with placebo 1. These medications work by mimicking the action of the naturally occurring hormone GLP-1, which regulates appetite and food intake. When administered, they slow gastric emptying, increase feelings of fullness, reduce hunger, and decrease caloric intake by acting on appetite centers in the brain. Some key points to consider when using these medications include:

• Typical dosing for liraglutide is a daily injection at a target dose of 3.0 mg, while semaglutide is given as a weekly injection starting at 0.25 mg and gradually increasing to 2.4 mg.
• Patients using these medications can expect weight loss of approximately 5-10% with liraglutide and 15-20% with semaglutide over 68 weeks of treatment.
• Common side effects include nausea, vomiting, diarrhea, and constipation, which often improve over time.
• These medications are most effective when combined with lifestyle modifications including diet and exercise, and require ongoing use to maintain weight loss benefits.
• They should be prescribed under medical supervision and are contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. It's also important to note that semaglutide has been shown to reduce the risk of cardiovascular events in adults with overweight or obesity without diabetes, with a hazard ratio of 0.80 (95% CI, 0.72-0.90) compared to placebo 1. Overall, semaglutide is the preferred choice for weight loss due to its superior efficacy and safety profile compared to liraglutide, as demonstrated in the STEP trials and other studies 1.

From the FDA Drug Label

Liraglutide lowers body weight through decreased calorie intake. Liraglutide does not increase 24-hour energy expenditure. GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. SAXENDA is a glucagon like peptide 1 (GLP-1) receptor agonist indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: • Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity • Adults with overweight in the presence of at least one weight-related comorbid condition

The role of GLP-1 receptor agonists, such as liraglutide (Saxenda) and semaglutide (Wegovy), in weight loss is to:

• Lower body weight through decreased calorie intake
• Regulate appetite and calorie intake by binding to and activating the GLP-1 receptor in the brain
• Be used in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients with obesity or overweight with at least one weight-related comorbid condition 2, 2, 2.

From the Research

GLP-1 Receptor Agonists in Weight Loss

• GLP-1 receptor agonists, such as liraglutide and semaglutide, have been shown to be effective in promoting weight loss in people with obesity or overweight 3, 4, 5, 6, 7.
• Semaglutide 2.4mg has been found to have an absolute advantage in weight loss and decreased HbA1c, but also has a higher incidence of total adverse events and can cause hypoglycemia 3.
• Liraglutide 3.0mg was less effective than semaglutide 2.4mg, but still had a significant weight loss effect, although with a higher incidence of serious adverse events 3.

Efficacy of GLP-1 Receptor Agonists

• A systematic review and 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 3.
• Another study found that semaglutide was well tolerated and showed clinically relevant weight loss compared to placebo at all doses 5.
• A randomized clinical trial found that once-weekly subcutaneous semaglutide 2.4mg resulted in significantly greater weight loss than once-daily subcutaneous liraglutide 3.0mg at 68 weeks 7.

Safety of GLP-1 Receptor Agonists

• The most common adverse events associated with GLP-1 receptor agonists are dose-related gastrointestinal symptoms, primarily nausea 5, 7.
• Semaglutide 2.4mg had a higher incidence of total adverse events and hypoglycemic events compared to liraglutide 3.0mg and semaglutide 1.0mg 3.
• Liraglutide 3.0mg had a higher incidence of serious adverse events compared to semaglutide 2.4mg and semaglutide 1.0mg 3.