GLP Medications

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This incretin hormone plays an active role in your digestion and appetite. Incretins, hormones released by your digestive tract, are sent out after you’ve eaten a meal. They help control blood sugar spikes, lower blood sugar, and slow down how quickly food leaves your stomach, allowing you to feel full longer. For many people, this can be the help they need to reduce their calorie intake to start losing weight and becoming healthier. 

Semaglutide, Tirzepatide, and Retatrutide are injectable medications that help with weight loss and blood sugar control. They work by mimicking natural hormones in your body that regulate appetite and blood sugar.  

All three medications are given as once-weekly injections (though semaglutide also comes as a daily pill). They all work by reducing appetite and helping you feel full longer.[5][3][8]  

In terms of effectiveness for weight loss:  

- Semaglutide: approximately 15-17% weight loss [3][4] at 72 weeks.

- Tirzepatide: approximately 15-21% weight loss [10][9] at 72 weeks.

- Retatrutide: approximately 17-24% weight loss (in early studies) [5][13] at 48 weeks.

For blood sugar control in people with type 2 diabetes, all three medications are effective, with tirzepatide and retatrutide showing slightly better results than semaglutide in research studies.[6][14][11] 

Semaglutide works by copying a single hormone called GLP-1, which helps you feel full and reduces your appetite. It is[1] FDA-approved for treating type 2 diabetes and for weight management in people with obesity or who are overweight with weight-related health problems. Semaglutide comes as a once-weekly injection or as a daily pill.[2][1]  

In clinical studies, people taking semaglutide for weight loss lost an average of about 15-17% of their body weight over approximately 2 years. Semaglutide has also been shown to reduce the risk of heart attacks, strokes, and other cardiovascular problems in people with heart disease and obesity.[3][4][2][5]  

Tirzepatide is a dual-action medication that mimics two hormones: GLP-1 and GIP. This combination appears to make it more effective than medications that only target GLP-1. Tirzepatide is[6][7][5][8] FDA-approved for treating type 2 diabetes and for weight management in people with obesity. It is given as a once-weekly injection.[2]  

In clinical studies, people taking tirzepatide for weight loss lost an average of about 15-21% of their body weight over 72 weeks (about 1.5 years). Head-to-head studies show that tirzepatide typically produces slightly more weight loss than semaglutide—about 4-5% more on average.[9][8][10][3]  

Retatrutide is a triple-action medication that targets three hormones: GLP-1, GIP, and glucagon that is currently in FDA clinical trials and is considered investigational. The addition of glucagon activity may help increase the body's energy burning and improve fat metabolism in the liver. Retatrutide is[11][5][12] not yet FDA-approved and is still being studied in clinical trials.[11]  

In early research studies, people taking Retatrutide lost an average of about 17-24% of their body weight over 48 weeks (about 1 year)! This represents the highest weight loss seen so far among these types of medications, though more research is needed to confirm these results.[5][13][14] 

The most common side effects for all three medications are digestive problems, including nausea, diarrhea, vomiting, and constipation. Other side effects, not listed, have been reported. These side effects are usually mild to moderate and often improve over time.[5][15][7] They tend to be more common with higher doses and when starting treatment.[11][15]  

Tirzepatide and retatrutide may cause slightly more digestive side effects than semaglutide, particularly at higher doses. Retatrutide can also increase heart rate.[13][11][16]  

All three medications carry warnings about potential risks of pancreatitis (inflammation of the pancreas), gallbladder problems, and low blood sugar (especially when combined with other diabetes medications).[11][15][7]  

- Semaglutide: Fully FDA-approved and available by prescription [2]  

- Tirzepatide: Fully FDA-approved and available by prescription [2]  

- Retatrutide: Not FDA-approved; only available through participation in clinical research studies [11] or compounding pharmacies. 

Important Considerations  

Compounded versions of investigational drugs are not approved by the FDA and may pose safety risks.[15] If receiving via compounding, choose a reputable in person clinic that is well established, like Revive Medical. Avoid telehealth companies and research peptide companies who offer low quality and dangerous products with very little, if any, oversight. 

All of these medications require a prescription and medical supervision. They work best when combined with healthy eating and regular physical activity. Weight regain is common if the medication is stopped, so these are typically considered long-term treatments.[2][8][15]  

This comparison provides a clear, accessible overview of the three medications while emphasizing that retatrutide remains investigational. The document focuses on practical differences in efficacy, safety, and availability that would be most relevant to patients making treatment decisions with their healthcare providers.  

1.  RYBELSUS. Food and Drug Administration. Updated date: 2025-10-17.

2.  FDA Orange Book. FDA Orange Book.

3.  Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ, Horn DB, le Roux CW, et al. The New England Journal of Medicine. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394.

4. Semaglutide as a Promising Antiobesity Drug. Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity. 2019;20(6):805-815. doi:10.1111/obr.12839.

5. New Molecules and Indications for GLP-1 Medicines. Gonzalez-Rellan MJ, Drucker DJ. JAMA. 2025;:2838996. doi:10.1001/jama.2025.14392.

6. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Davies MJ, Aroda VR, Collins BS, et al. Diabetes Care. 2022;45(11):2753-2786. doi:10.2337/dci22-0034.

7. Tirzepatide: A Review in Type 2 Diabetes. France NL, Syed YY. Drugs. 2024;84(2):227-238. doi:10.1007/s40265-023-01992-4.

8. Clinical Management of Obesity – Third Edition. Caroline M. Apovian MD, Louis Aronne MD, Sarah R. Barenbaum MD. The Obesity Society (2025).

9. Obesity Management in Adults: A Review. Elmaleh-Sachs A, Schwartz JL, Bramante CT, et al. JAMA. 2023;330(20):2000-2015. doi:10.1001/jama.2023.19897.

10. Subcutaneously Administered Tirzepatide vs Semaglutide for Adults With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. Karagiannis T, Malandris K, Avgerinos I, et al. Diabetologia. 2024;67(7):1206-1222. doi:10.1007/s00125-024-06144-1.

11. Retatrutide, a GIP, GLP-1 and Glucagon Receptor Agonist, for People With Type 2 Diabetes: A Randomised, Double-Blind, Placebo and Active-Controlled, Parallel-Group, Phase 2 Trial Conducted in the USA. Rosenstock J, Frias J, Jastreboff AM, et al. Lancet (London, England). 2023;402(10401):529-544. doi:10.1016/S0140-6736(23)01053-X.

12. The Power of Three: Retatrutide's Role in Modern Obesity and Diabetes Therapy. Abdul-Rahman T, Roy P, Ahmed FK, et al. European Journal of Pharmacology. 2024;985:177095. doi:10.1016/j.ejphar.2024.177095.

13. Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. Sinha B, Ghosal S. Obesity (Silver Spring, Md.). 2025;. doi:10.1002/oby.24360.

14. Beyond GLP-1: Efficacy and Safety of Dual and Triple Incretin Agonists in Personalized Type 2 Diabetes Care-a Systematic Review and Network Meta-Analysis. Yan K, Yu H, Blaise B. Acta Diabetologica. 2025;:10.1007/s00592-025-02534-y. doi:10.1007/s00592-025-02534-y.

15. 2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on Medical Weight Management for Optimization of Cardiovascular Health: A Report of the American College of Cardiology Solution Set Oversight Committee. Gilbert O, Gulati M, Gluckman TJ, et al. Journal of the American College of Cardiology. 2025;86(7):536-555. doi:10.1016/j.jacc.2025.05.024.

16. Evaluation and Comparison of Efficacy and Safety of Tirzepatide and Semaglutide in Patients With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis. Ding Y, Shi Y, Guan R, et al. Pharmacological Research. 2024;199:107031. doi:10.1016/j.phrs.2023.107031.