Understanding Retatrutide and Semaglutide: Key Differences in Development and Use

Mechanism of Action

Semaglutide

• Mimic the GLP-1 incretin hormone
  
• May enhance insulin secretion in response to elevated blood glucose
  
• May suppress glucagon secretion
  
• Slow gastric emptying
  
• Promote satiety
  
  

Retatrutide

• Triple agonist targeting GLP-1, GIP, and glucagon receptors
  
• GLP-1 and GIP pathways may increase insulin secretion and satiety
  
• Glucagon receptor activation may promote energy expenditure
  
• Designed to address multiple metabolic pathways for a comprehensive treatment effect ²

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Clinical Efficacy

Clinical Research: Weight Reduction

• Semaglutide (2.4 mg weekly):
  In the STEP 1 trial, semaglutide was associated with an average weight loss of approximately 15% over 68 weeks. In that study, 86.4% of participants achieved at least 5% weight loss. These results were observed in a clinical setting using an FDA-approved medication under provider supervision.¹
• Retatrutide (12 mg weekly):
  In a 48-week phase 2 trial, the investigational drug retatrutide was associated with up to 24.2% average weight loss in certain populations. In that trial, 100% of participants achieved at least 5% weight loss, and 88% achieved 15% or more. Retatrutide has not been approved for use and remains under clinical investigation.²
  
  

Glycemic Control

• Semaglutide:
  In clinical trials involving individuals with type 2 diabetes, semaglutide has been associated with an average HbA1c reduction of approximately 1.5%.³
• Retatrutide:
  In a phase 2 study, the investigational drug retatrutide was associated with HbA1c reductions of up to 2.2% in participants with type 2 diabetes.⁴ Retatrutide is not FDA-approved and remains under clinical investigation.

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Safety and Side Effects

GLP-1 Medications

• Common side effects may include nausea, vomiting, diarrhea, and constipation
  
• Rare but serious risks may include gallbladder disease and pancreatitis
  
• Side effects are often temporary and may improve over time ¹
  
  

Retatrutide

• Similar gastrointestinal symptoms have been observed in trials
  
• Long-term safety and tolerability remain under investigation
  
• More data are needed to establish safety in larger populations ²
  
  

Conclusion

Retatrutide is an investigational medication that targets GLP-1, GIP, and glucagon receptors. Early clinical studies have reported promising findings, including weight loss and HbA1c reductions in specific trial populations. However, retatrutide is still in development and has not been approved by the FDA.

In contrast, GLP-1 receptor agonists such as semaglutide are FDA-approved and have been studied extensively for type 2 diabetes management and chronic weight control. All treatment decisions should be made in consultation with a licensed provider.

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For individuals considering metabolic treatment options, consultation with a licensed healthcare provider is essential to evaluate eligibility, medical history, and therapeutic goals.

Eden connects patients with licensed providers who can assess your eligibility for GLP-1 medications. Your provider will guide your treatment, monitor for side effects, and adjust your care plan as needed.

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