What are the benefits of Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (glucagon-like peptide-1 receptor agonist) or semaglutide (glucagon-like peptide-1 receptor agonist), for weight loss?

From the Guidelines

GLP-1 receptor agonists, such as semaglutide and liraglutide, are highly effective for weight loss, with semaglutide showing the most impressive results of up to 15-20% weight reduction in clinical studies. The primary benefits of these medications include appetite suppression, delayed gastric emptying, and improved blood sugar control. Patients using these medications report feeling satisfied with smaller portions and experiencing fewer food cravings. Typical dosing involves weekly injections for semaglutide (starting at 0.25mg and gradually increasing to 2.4mg) or daily injections for liraglutide (building up to 3.0mg) 1.

Key Benefits of GLP-1 Receptor Agonists

• Appetite suppression through direct action on brain centers that control hunger
• Delayed gastric emptying which promotes feelings of fullness
• Improved blood sugar control
• Reduced cardiovascular risk, as shown in the SELECT study where semaglutide reduced the incidence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke in patients with pre-existing CVD who were overweight or obese, but without diabetes 1
• Improved liver function in fatty liver disease and better blood pressure control

Side Effects and Management

• Nausea, vomiting, and diarrhea are the most frequently reported adverse effects, which are dose-dependent and can be managed with slow titration and dietary adjustments 1
• Rare adverse effects include acute pancreatitis and cardiac arrhythmia/tachycardia, which require careful monitoring and management

Clinical Evidence

• The STEP trials demonstrated the efficacy of semaglutide for weight loss, with mean weight loss of 14.9% and 16.0% at 68 weeks, compared to 2.4% and 5.7% with placebo, respectively 1
• The SURMOUNT-1 trial showed a dose-dependent weight-loss benefit with tirzepatide, a combined GLP-1 and GIP receptor agonist, with a mean weight loss of up to 20.9% at 72 weeks 1

Recommendation

Semaglutide is the preferred GLP-1 receptor agonist for weight loss due to its superior efficacy and safety profile, as demonstrated in the most recent and highest-quality studies 1. However, liraglutide is also an effective option, particularly for patients who prefer daily injections or have concerns about the cost and availability of semaglutide. Ultimately, the choice of medication should be individualized based on patient preferences, medical history, and lifestyle.

From the FDA Drug Label

Semaglutide lowers fasting and postprandial blood glucose and reduces body weight. All pharmacodynamic evaluations were performed after 12 weeks of treatment (including dose escalation) at steady state with semaglutide 1 mg.

The GLP-1 receptor agonist, semaglutide, has been shown to have benefits for weight loss.

• It reduces body weight in patients with type 2 diabetes.
• The mechanism of weight loss is not fully explained in the provided text, but it is associated with a reduction in blood glucose and an increase in insulin secretion.
• Semaglutide also causes a delay in gastric emptying, which may contribute to weight loss. 2

From the Research

Benefits of GLP-1 Receptor Agonists for Weight Loss

The benefits of Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, for weight loss are numerous. Some of the key benefits include:

• Weight loss: GLP-1 receptor agonists have been shown to result in significant weight loss in obese individuals, with studies demonstrating an average weight loss of 5-15% 3, 4, 5, 6.
• Improved metabolic parameters: GLP-1 receptor agonists have been shown to improve metabolic parameters such as glucose metabolism, hypertension, and dyslipidemia 4, 6, 7.
• Reduced cardiovascular risk: GLP-1 receptor agonists have been shown to reduce cardiovascular risk factors such as triglycerides and increase HDL cholesterol, and have also been shown to reduce cardiovascular mortality and non-fatal myocardial infarction or stroke 7.
• Improved liver function: GLP-1 receptor agonists have been shown to improve liver function in patients with metabolic dysfunction-associated steatotic liver disease 7.

Mechanism of Action

The mechanism of action of GLP-1 receptor agonists involves mimicking the effects of the incretin hormone GLP-1, which is involved in regulating appetite and food intake. GLP-1 receptor agonists have been shown to reduce food intake and increase satiety, leading to weight loss 3, 5.

Clinical Evidence

Clinical trials have demonstrated the efficacy and safety of GLP-1 receptor agonists for weight loss. For example, liraglutide 3 mg daily has been associated with greater weight loss than placebo or orlistat in patients without type 2 diabetes 6. Semaglutide 2.4 mg sc has also been shown to result in significant weight loss and improvements in cardiometabolic parameters 7.

Potential for Future Treatment

The use of GLP-1 receptor agonists for weight loss represents a promising approach for the treatment of obesity. Future studies are needed to fully elucidate the potential of these agents for weight loss and to determine their long-term safety and efficacy 3, 4, 5, 6, 7.