From the Guidelines
GLP-1 receptor agonists, particularly semaglutide, are the most effective treatment options for weight loss in individuals with obesity or overweight conditions, with a mean weight loss of 14.9% to 16.0% at 68 weeks, as demonstrated in the STEP trials 1.
Treatment Options
The most commonly prescribed GLP-1 receptor agonists include:
- Semaglutide (Wegovy), typically starting at 0.25mg weekly and gradually increasing to 2.4mg weekly over 16-20 weeks
- Liraglutide (Saxenda), starting at 0.6mg daily and increasing to 3.0mg daily These medications work by mimicking the hormone GLP-1, which helps regulate appetite and food intake by increasing feelings of fullness, slowing stomach emptying, and affecting brain centers that control hunger.
Efficacy and Safety
Studies have shown that GLP-1 receptor agonists result in substantially greater weight loss in those without diabetes (mean weight loss 6.1–17.4%) compared with patients with diabetes (4–6.2%) 1. The STEP trials demonstrated that weekly semaglutide (2.4 mg) reduced the mean body weight from baseline by 14.9% in patients who were non-diabetic, overweight or obese 1. Common side effects include nausea, vomiting, diarrhea, and constipation, which typically improve over time.
Lifestyle Modifications and Long-term Treatment
For optimal results, GLP-1 receptor agonists should be used alongside lifestyle modifications including calorie reduction and increased physical activity. Treatment is typically long-term as weight regain commonly occurs when medication is discontinued, with a mean weight regain of 11.6% of lost weight after cessation of semaglutide 1. Regular medical follow-up is essential to monitor progress and manage any side effects.
Cardiovascular Benefits
GLP-1 receptor agonists have also been shown to decrease 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) in the SELECT study 1. The cardioprotective effects of GLP-1 receptor agonists are mediated by several mechanisms, including improved myocardial substrate utilization, anti-inflammatory and anti-atherosclerotic effects, reduced myocardial ischemia injury, and lower systemic and pulmonary vascular resistance 1.
From the Research
Treatment Options for Weight Loss using GLP-1 Receptor Agonists
- GLP-1 receptor agonists have been shown to be effective in achieving substantial weight loss and improving cardiometabolic risk factors 2
- Liraglutide, a GLP-1 receptor agonist, has been associated with a mean weight loss of 4-7 kg, with more than 50% of treated individuals achieving 5% or more weight loss 2
- Semaglutide, another GLP-1 receptor agonist, has been shown to have a greater impact on weight loss, with a mean weight loss of 9-16 kg, and more than 50% of treated individuals achieving 10-15% or more weight loss 2
- Tirzepatide, a dual GIP/GLP-1 receptor agonist, has been shown to induce a weight loss of about 20% in obese people without diabetes 3
Comparison of Different GLP-1 Receptor Agonists
- Semaglutide has been shown to have a greater mean weight loss compared to liraglutide and dulaglutide 4
- Tirzepatide has been shown to have a greater mean weight loss compared to semaglutide 4
- The most frequently encountered adverse events with GLP-1 receptor agonists are gastrointestinal symptoms, including nausea, vomiting, obstipation, or diarrhea 3, 2, 4
Potential Approaches to Potentiate Weight Loss
- Increasing the drug dosage, as there is a demonstrated dose-response relationship 5
- Add-on therapy with a sodium-glucose cotransporter type 2 inhibitor, which exerts a complementary action through urinary calorie loss (glucosuria) 5
- Combination of the effects of two incretin hormones (GLP-1 and GIP), as with the potent dual agonist tirzepatide 5