What is the safety and efficacy of using Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Saxenda) (liraglutide) and semaglutide (Wegovy) (semaglutide), for cosmetic weight loss in individuals without obesity-related health conditions?

From the Guidelines

GLP-1 receptor agonists like liraglutide (Saxenda) and semaglutide (Wegovy) are not recommended for purely cosmetic weight loss in individuals without obesity-related health conditions. These medications are FDA-approved specifically for chronic weight management in adults with a BMI of 30 kg/m² or greater (obesity), or 27 kg/m² or greater (overweight) with at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia. While these medications have demonstrated efficacy with average weight loss of 5-15% of body weight when used alongside lifestyle modifications, they carry significant risks including gastrointestinal side effects (nausea, vomiting, diarrhea), pancreatitis, gallbladder disease, and potential thyroid tumors, as reported in a study published in JAMA 1. They also require ongoing use to maintain weight loss effects, with weight regain common upon discontinuation. Additionally, these medications are expensive (often $1,000-$1,500 monthly), frequently not covered by insurance for cosmetic purposes, and their long-term safety beyond clinical trial durations remains under investigation.

Key Considerations

• The use of GLP-1 receptor agonists for cosmetic weight loss is not supported by current evidence and guidelines, including those from the AGA 1.
• These medications have been shown to be effective for weight loss in individuals with obesity or overweight with weight-related complications, but their use in individuals without these conditions is not recommended.
• The potential risks and side effects of GLP-1 receptor agonists, such as pancreatitis and thyroid tumors, must be carefully considered, as highlighted in a study published in Obesity Reviews 1.
• Evidence-based lifestyle interventions, including dietary changes, regular physical activity, and behavioral modifications, remain the recommended first-line approach for individuals seeking weight management without obesity-related conditions.

Safety and Efficacy

• The safety and efficacy of GLP-1 receptor agonists have been evaluated in several studies, including the STEP trials, which demonstrated significant weight loss and improvement in weight-related comorbidities 1.
• However, these studies also highlighted the potential risks and side effects of these medications, including gastrointestinal side effects and pancreatitis.
• The long-term safety of GLP-1 receptor agonists beyond clinical trial durations remains under investigation, as noted in a study published in Diabetes Care 1.

Recommendations

• GLP-1 receptor agonists should not be used for purely cosmetic weight loss in individuals without obesity-related health conditions.
• These medications should only be used in individuals with a BMI of 30 kg/m² or greater (obesity), or 27 kg/m² or greater (overweight) with at least one weight-related comorbidity, and under the guidance of a healthcare professional.
• Evidence-based lifestyle interventions should be recommended as the first-line approach for individuals seeking weight management without obesity-related conditions.

From the Research

Safety and Efficacy of GLP-1 Receptor Agonists for Cosmetic Weight Loss

• The use of Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, for cosmetic weight loss in individuals without obesity-related health conditions has been studied in several trials 2, 3, 4, 5, 6.
• A study published in 2021 suggested that GLP-1 receptor agonists can be used for weight loss in patients who are overweight without weight-related comorbidity, with shared decision making to address each medication's key limitation 2.
• Another study published in 2021 discussed the mechanism of action of GLP-1 receptor agonists in weight loss and longer-term maintenance of weight loss, and the efficacy and safety of this treatment class 3.
• A living benefit-harm modelling study published in 2024 evaluated the benefit-harm balance of initiating GLP-1 receptor agonists versus placebo for weight loss in people living with overweight and obesity but without diabetes, and found that achieving a 10% weight loss with GLP-1 receptor agonist therapy outweighed the cumulative harms 4.
• A review published in 2024 discussed the use of oral GLP-1 receptor agonists for weight loss, including semaglutide, danuglipron, and orforglipron, with a focus on oral semaglutide 5.
• A report published in 2022 discussed the evidence supporting the use of GLP-1 receptor agonists to treat obesity and their role as a cardioprotective drug, and highlighted the potential of GLP-1 receptor agonists to decrease cardiovascular risk 6.

Key Findings

• GLP-1 receptor agonists can produce significant weight loss in individuals without obesity-related health conditions 2, 3, 4.
• The safety and efficacy of GLP-1 receptor agonists for cosmetic weight loss depend on the specific medication and dose used, as well as individual patient factors 2, 3, 4.
• Oral semaglutide is a promising option for weight loss, with a focus on its potential to increase availability to patients 5.
• GLP-1 receptor agonists have been shown to decrease cardiovascular risk in patients with type 2 diabetes, and may have a similar effect in individuals without diabetes 6.

Medications and Doses

• Liraglutide 1.8 mg daily and 3.0 mg daily have been shown to produce significant weight loss 2, 3.
• Semaglutide 2.4 mg weekly has been investigated in phase III trials for obesity management 3.
• Oral semaglutide has been approved by the Food and Drug Administration for type 2 diabetes, but not for obesity alone 5.