Weight Loss
What to Know About GLP-1 Medications and Weight Management Programs
Learn how Eden connects patients to licensed providers to explore GLP-1 medications as part of medical weight management programs.
Retatrutide vs. Semaglutide Medications: A Comparative Overview
Carson @ Eden
Compare GLP-1 medications like semaglutide with retatrutide, a triple agonist under study. See how they differ in efficacy, safety, and approval status.
Key takeaways
- GLP-1 medications like semaglutide are FDA-approved, while retatrutide is investigational and still in clinical trials 1 2.
- Semaglutide is associated with approximately 15% weight loss over 68 weeks, whereas retatrutide showed up to 24.2% weight loss over 48 weeks 1 2.
- Retatrutide reduced HbA1c by up to 2.2%, compared to 1.5% with semaglutide 3 4.
- Both therapies may cause gastrointestinal side effects. Retatrutide’s long-term safety remains under investigation 1 2.
GLP-1 receptor agonists, such as semaglutide, are FDA-approved medications used to manage type 2 diabetes and support chronic weight management. In contrast, retatrutide is an investigational triple-hormone receptor agonist that targets GLP-1, GIP, and glucagon receptors. It is currently under clinical evaluation and not approved for use.
This article compares semaglutide and retatrutide based on available clinical research, focusing on mechanism of action, clinical outcomes, and safety.
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider. Eden connects individuals with licensed providers who offer personalized treatment plans.
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
Clinical Efficacy
Weight Reduction
- Semaglutide (2.4 mg weekly):
In the STEP 1 trial, semaglutide led to approximately 15% mean weight loss over 68 weeks.
86.4% of participants achieved ≥5% weight loss 1. - Retatrutide (12 mg weekly):
In a 48-week phase 2 trial, retatrutide led to up to 24.2% mean weight loss.
100% achieved ≥5% weight loss, and 88% achieved ≥15% weight loss 2.
Glycemic Control
- Semaglutide:
Reduced HbA1c by approximately 1.5% in individuals with type 2 diabetes 3 - Retatrutide:
In a phase 2 study, HbA1c reduction reached 2.2% in participants with type 2 diabetes 4
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. It has shown encouraging results in early studies, including up to 24.2% weight loss and greater HbA1c reductions compared to existing GLP-1 therapies. However, it remains under clinical investigation and is not FDA-approved.
In contrast, GLP-1 receptor agonists such as semaglutide are FDA-approved and supported by extensive clinical data for both weight management and glycemic control.
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 prescribe personalized GLP-1 medications. Your provider will guide your treatment, monitor for side effects, and adjust your care plan as needed.
Disclaimer: The FDA does not approve compounded medications for safety, quality, or manufacturing. Prescriptions and a medical evaluation are required for certain products. The information provided on this blog is for general informational purposes only. It is not intended as a substitute for professional advice from a qualified healthcare professional and should not be relied upon as personal health advice. The information contained in this blog is not meant to diagnose, treat, cure, or prevent any disease. Readers are advised to consult with a qualified healthcare professional for any medical concerns, including side effects. Use of this blog's information is at your own risk. The blog owner is not responsible for any adverse effects or consequences resulting from the use of any suggestions or information provided in this blog.
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References
- Wilding JPH, et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
- Jastreboff AM, et al. (2023). Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- Zweck E, Westenfeld R, Szendroedi J. Oral Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 https://www.nejm.org/doi/10.1056/NEJMc1913157
- Abdrabou Abouelmagd, A., … (2025). Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials. Baylor University Medical Center Proceedings, 38(3), 291–303. https://pmc.ncbi.nlm.nih.gov/articles/PMC12026077/