From the Guidelines
No, a GLP-1 antagonist would not be effective for treating obesity, as the most recent and highest quality evidence supports the use of GLP-1 agonists, such as semaglutide and liraglutide, for weight loss. The medications that help with weight loss are actually GLP-1 agonists (not antagonists), which mimic the action of natural GLP-1 hormone, helping to regulate blood sugar and appetite 1. A GLP-1 antagonist would block the action of GLP-1, which would likely increase hunger and potentially lead to weight gain rather than weight loss. GLP-1 agonists work by slowing stomach emptying, increasing feelings of fullness, reducing appetite, and improving blood sugar control. They typically produce weight loss of 10-20% of body weight when used alongside lifestyle modifications, as seen in the STEP trials, which examined the efficacy of semaglutide 1.
Some key points to consider when using GLP-1 agonists for weight loss include:
- The importance of long-term use, as weight regain is common after cessation of treatment 1
- The potential for improved weight-related comorbidities and reduced risk of cardiovascular events 1
- The availability of different formulations, such as subcutaneous semaglutide and liraglutide, as well as oral semaglutide, which is not yet FDA approved for obesity alone 1
- The need for individualized treatment plans, taking into account patient values and preferences, as well as potential adverse effects and treatment discontinuation 1
Overall, the use of GLP-1 agonists, such as semaglutide and liraglutide, is supported by the most recent and highest quality evidence for the treatment of obesity, and GLP-1 antagonists are not recommended for this indication.
From the Research
GLP-1 Antagonist for Obesity
- There is no evidence to suggest that a GLP-1 antagonist is effective for treating obesity. In fact, the studies suggest that GLP-1 receptor agonists, not antagonists, are effective for obesity treatment 2, 3, 4, 5, 6.
- GLP-1 receptor agonists have been shown to achieve substantial weight loss and improve cardiometabolic risk factors, making them a promising approach for obesity treatment 2, 3, 4.
- The use of GLP-1 receptor agonists, such as liraglutide and semaglutide, has been evaluated in several clinical trials and has led to regulatory approval for weight loss in individuals with obesity, regardless of diabetes status 2, 6.
- The benefits of GLP-1 receptor agonists extend to other risk factors, such as glycemic control and blood pressure, and they are expected to have a critical role in the management of obesity in the coming years 2, 4.
Mechanism of Action
- GLP-1 receptor agonists work by activating the GLP-1 receptor, which helps to reduce body weight by promoting satiety and delaying gastric emptying 6.
- The extrapancreatic actions of GLP-1 receptor agonists, both peripheral and central, also contribute to their weight-loss effects 6.
Clinical Evidence
- Clinical trials have demonstrated that GLP-1 receptor agonists, such as liraglutide and semaglutide, can achieve significant weight loss, with mean weight losses ranging from 4-16 kg 2, 6.
- The use of GLP-1 receptor agonists has also been shown to improve cardiometabolic risk factors, such as glycemic control and blood pressure 2, 4.