Retatrutide (LY3437943)

Triple GLP-1/GIP/Glucagon Agonist · Weight Loss & Diabetes

Overview

Novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials demonstrated 24.2% weight loss at 48 weeks—the highest recorded for obesity medications.

Activates GLP-1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.

Clinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.

Continuous weight loss with no plateau at 48 weeks suggests greater long-term potential.

Addresses obesity through appetite suppression, energy expenditure, and metabolic efficiency.

HbA1c reductions up to 2.16% with 82% achieving target levels below 6.5%.

Mechanism

Novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials demonstrated 24.2% weight loss at 48 weeks—the highest recorded for obesity medications.

Activates GLP-1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.

Clinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.

Research areas

Novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials demonstrated 24.2% weight loss at 48 weeks—the highest recorded for obesity medications.
Activates GLP-1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.
Clinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.
Continuous weight loss with no plateau at 48 weeks suggests greater long-term potential.
Addresses obesity through appetite suppression, energy expenditure, and metabolic efficiency.
HbA1c reductions up to 2.16% with 82% achieving target levels below 6.5%.
Balanced glycemic control with minimal hypoglycemia risk.
Marked improvements in sensitivity with potential for reduced exogenous insulin requirements.
Non-HDL cholesterol reductions up to 26.9%, triglyceride reductions up to 40.6%.
Consistent decreases in systolic and diastolic blood pressure across trials.
Up to 82% reduction in liver fat with normalization in 90% of participants.

Research notes

Gastrointestinal effects (nausea, vomiting, diarrhea)—typically mild to moderate
Heart rate increases—common especially in first 24 weeks
Appetite suppression
Mild dehydration
Severe persistent nausea or vomiting preventing adequate nutrition
Signs of pancreatitis: severe abdominal pain radiating to back
Severe hypoglycemia symptoms: confusion, dizziness, sweating
Excessive weight loss (>3 lbs per week consistently or >25% total body weight)
Gallbladder problems: severe right upper abdominal pain
Personal or family history of medullary thyroid carcinoma
MEN2 syndrome
Severe renal impairment
Triple agonism means triple GI effects. GLP-1, GIP, and glucagon all slow gastric emptying and affect GI motility. Combining three mechanisms means more nausea, diarrhea, and vomiting, especially during dose escalation. However, most people tolerate it by week 4-8 as their body adapts.

AXIOM catalogue

Retatrutide — research-use catalogue record with strengths and available batch details where listed.

References

FAQs

What makes retatrutide's 24.2% weight loss so much higher than semaglutide's 15-20%?

Retatrutide is a triple agonist activating GLP-1, GIP, and glucagon receptors simultaneously. GLP-1 suppresses appetite, GIP improves insulin sensitivity, and glucagon increases energy expenditure and fat oxidation. Semaglutide only activates GLP-1. The triple mechanism addresses obesity through three distinct pathways, explaining the superior results.

Does retatrutide actually reduce liver fat, or just overall fat loss?

It specifically targets liver fat. Clinical trials showed up to 82% liver fat reduction and complete normalization in 90% of participants at 24 weeks. This isn't just general weight loss—it's preferential hepatic fat oxidation, making retatrutide potentially valuable for NAFLD/MASH, not just obesity.

Could I eventually stop taking retatrutide, or do I need it forever?

Unknown. Phase 2 trials ran 48 weeks—long enough to achieve 24% weight loss but not long enough to study discontinuation. Clinical experience with semaglutide suggests weight returns if stopped. Phase 3 TRIUMPH trials (results expected 2026) should provide data on maintenance therapy vs. indefinite use.