1. Semaglutide (e.g., Ozempic, Wegovy):
• GLP-1 receptor agonist.
• Enhances insulin secretion, slows gastric emptying, and promotes satiety.
2. Tirzepatide (e.g., Mounjaro):
• Dual GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist.
• Adds a second pathway (GIP) that enhances insulin release and fat metabolism.
3. Retatrutide :
• Triple agonist targeting GLP-1, GIP, and glucagon receptors.
• Glucagon action may enhance energy expenditure and fat oxidation.

Benefits Comparison

1. Weight Loss

• Semaglutide: Associated with 15–20% body weight reduction in clinical trials at higher doses (e.g., Wegovy).
• Tirzepatide: Demonstrated superior weight loss, up to 22.5% in studies, likely due to its dual action.
• Retatrutide: Early trials report even greater weight loss, exceeding 24% in some cases, potentially making it the most effective.

2. Glycemic Control

• Semaglutide: Strongly improves HbA1c levels and reduces fasting glucose.
• Tirzepatide: Slightly superior to Semaglutide in HbA1c reduction due to its dual agonist mechanism.
• Retatrutide: Preliminary data suggests it may offer even better glycemic control by combining GLP-1, GIP, and glucagon effects.

3. Energy Expenditure

• Semaglutide and Tirzepatide: Focus on reducing appetite and caloric intake.
• Retatrutide: Adds glucagon receptor activation, which may boost energy expenditure and promote fat oxidation, offering a unique advantage.

4. Cardiovascular Benefits

• Semaglutide: Proven cardiovascular benefits, including reduced risk of heart attack and stroke.
• Tirzepatide: Emerging evidence suggests similar cardiovascular protection, possibly better than Semaglutide.
• Retatrutide: Cardiovascular outcomes are still being studied, but it could potentially provide similar or superior benefits.

5. Side Effects

• Semaglutide and Tirzepatide:Common side effects include nausea, vomiting, diarrhea, and gastrointestinal discomfort, typically dose-dependent.
• Retatrutide: Preliminary data shows similar gastrointestinal side effects, though tolerability remains under investigation.

Potential Advantages of Retatrutide

1. Greater Efficacy: Offers the most significant weight loss and glycemic control among the three drugs due to its triple-agonist mechanism.

2. Fat Oxidation: Unique glucagon activation may promote additional fat loss and metabolic benefits.
3. Next-Generation Option: As an investigational therapy, Retatrutide has the potential to address limitations of current treatments.

Summary

• Semaglutide: Highly effective and well-established, excellent for weight loss and diabetes control.
• Tirzepatide: More potent for weight loss and glycemic control due to dual agonism.
• Retatrutide: Data suggests it may surpass both in weight loss, glycemic control, and metabolic benefits due to its triple agonism.