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Clinical Studies and Weight Loss: A Guide to Semaglutide, Tirzepatide, and Retatrutide This document provides a simple overview of three peptides – Semaglutide, Tirzepatide, and Retatrutide, These are currently being used with great success for weight loss and blood sugar control. It's important to remember that this information is for general knowledge, and you should always talk to your doctor before starting any new medication. Semaglutide (Sem) GLP-1 (Ozempic, Wegovy) How it works: Semaglutide mimics a natural hormone in your body called GLP-1. This hormone helps regulate your appetite and blood sugar. What it's used for: Treating type 2 diabetes by controlling blood sugar. Helping with weight loss and maintaining weight loss in people with obesity or those that are overweight and have at least one weight-related health condition. Lowering the risk of heart attack, stroke, and other heart-related problems in people with type 2 diabetes and heart disease. Weight Loss Results: Demonstrated clinically significant and sustained weight loss over extended periods (up to 4 years) in individuals with obesity and those that were overweight, even without type 2 diabetes (SELECT trial). Results show an average of 10.2% weight reduction at 208 weeks compared to placebo. Used for chronic weight management in conjunction with diet and exercise. Important Considerations: May not be suitable for people with a history of pancreatitis, thyroid cancer, or severe digestive problems. It should not be used in people with type 1 diabetes, or diabetic ketoacidosis. It may increase risk of pulmonary aspiration during operations. It may worsen diabetic retinopathy. Can cause side effects like nausea, vomiting, diarrhea, and other gastrointestinal issues. Benefits: Has been on the market the longest amount of time and has a great deal of supporting data. Has shown to reduce cardiovascular risk. Tirzepatide (Tir) GLP-2 (Mounjaro, Zepbound) How it works: Tirzepatide activates two hormone receptors (GIP and GLP-1), which may lead to even greater effects on appetite and blood sugar control compared to Semaglutide. The addition of GIP receptor activation appears to enhance the effects of the medication. What it's used for: Helping with weight loss in people with obesity or those that are overweight and have at least one weight-related health condition. The FDA has approved Zepbound for the treatment of moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity. Treating type 2 diabetes. Weight Loss Results: Average weight loss of 20.2% at 72 weeks (SURMOUNT-5 trial). Approved for chronic weight management in adults with obesity or those that are overweight with at least one weight-related condition. Studies show a 47% greater relative weight loss when compared to Semaglutide. Important Considerations: Should not be used by individuals with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2). Should be used cautiously in patients with severe gastrointestinal diseases or a history of pancreatitis. Can cause side effects like nausea, vomiting, diarrhea, constipation, indigestion, and other gastrointestinal issues. Benefits: May offer superior weight loss results. New research shows that Tirzepatide can effectively lower inflammation. Retatrutide (Ret) GLP-3 How it works: Retatrutide is a "tri-agonist," meaning it activates three hormone receptors (GLP-1, GIP, and glucagon). What it's used for: Currently being studied for weight loss. Weight Loss Results: Phase II trials showed significant weight reduction, with average losses of 17.5% and 24.4% at 24 and 48 weeks, respectively. Early clinical trials indicate potentially higher weight loss than both Semaglutide and Tirzepatide. Important Considerations: Like the other two medications, gastrointestinal side effects are possible.. Benefits: Shows very promising early results for significant weight loss. Current Research of Interest Click on the title links below for more information FDA Approves First Medication for Obstructive Sleep Apnea Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial Semaglutide for weight loss - what you need to know Long-term weight loss effects of Semaglutide in obesity without diabetes in the SELECT trial SEMAGLUTIDE: Weight loss, glycemic control and safety profile in obese patients with and without type-II Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity Tirzepatide Outperforms Semaglutide in Weight Loss Trial The power of three: Retatrutide's role in modern obesity and diabetes therapy Recent advances in peptide-based therapies for obesity and type 2 diabetes Stanford-Naturally occurring molecule rivals Ozempic in weight loss, sidesteps side effects Semaglutide - Mayo Clinic

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