Retatrutide: Complete UK Research Guide (2025)

What Is Retatrutide?

Retatrutide is an investigational peptide developed by Eli Lilly, the same pharmaceutical company behind tirzepatide (sold as Mounjaro and Zepbound). It belongs to a new class of compounds called triple agonists because it activates three different hormone receptors in the body.

The compound is sometimes called "Triple G" because it targets three receptors that all play a role in glucose and energy regulation. Eli Lilly has filed for the brand name Alluvi for the eventual commercial product.

Retatrutide represents the next step in incretin-based research. While semaglutide targets one receptor (GLP-1) and tirzepatide targets two (GLP-1 and GIP), retatrutide adds a third target: the glucagon receptor.

How Does Retatrutide Work?

To understand retatrutide, you first need to know about the three receptors it targets. Each one plays a different role in how the body handles food, energy, and fat storage.

GLP-1 Receptor (Glucagon-Like Peptide-1)

GLP-1 is a hormone released by your gut after eating. It tells your brain you're full, slows down how fast food leaves your stomach, and helps control blood sugar by triggering insulin release.

Drugs like semaglutide (Ozempic, Wegovy) work by mimicking GLP-1. They make you feel fuller for longer and reduce appetite.

GIP Receptor (Glucose-Dependent Insulinotropic Polypeptide)

GIP is another gut hormone released after meals. It also stimulates insulin release and appears to affect how the body stores and uses fat. Research suggests GIP may enhance the effects of GLP-1 when both are activated together.

Tirzepatide (Mounjaro) targets both GLP-1 and GIP receptors, which may explain why it produces greater weight loss than GLP-1-only drugs in clinical trials.

Glucagon Receptor

This is what makes retatrutide different. Glucagon is a hormone that raises blood sugar by telling the liver to release stored glucose. It also increases energy expenditure and promotes the breakdown of fat for fuel.

Adding glucagon receptor activation to the mix may help the body burn more calories and fat, even at rest. This third mechanism could explain the higher weight loss percentages seen in retatrutide trials compared to tirzepatide.

Why Triple Action Matters

By targeting all three receptors, retatrutide affects appetite, digestion, insulin response, and energy expenditure at the same time. Early research suggests this combination produces greater metabolic effects than targeting one or two receptors alone.

Clinical Trial Results

Retatrutide has shown strong results in clinical trials, with weight loss percentages exceeding those seen with tirzepatide and semaglutide.

Phase 2 Trial Data

The main Phase 2 trial results were published in The New England Journal of Medicine in 2023. This 48-week study tested different doses of retatrutide in adults with obesity.

At the highest dose (12mg), participants lost an average of 24.2% of their body weight in less than a year. Some participants in the 12mg group lost over 30% of their starting weight.

For comparison:

• Semaglutide (Wegovy) produces around 15-17% weight loss over 68 weeks
• Tirzepatide (Mounjaro) produces around 20-22% weight loss over 72 weeks

Phase 3 Trials

Several Phase 3 trials are currently underway to confirm these results in larger populations. These trials are testing retatrutide for:

• Obesity and weight management
• Type 2 diabetes
• Cardiovascular outcomes
• Non-alcoholic fatty liver disease (NAFLD/NASH)

Phase 3 trials typically take 2-3 years to complete. Based on current timelines, regulatory submissions could begin in 2026-2027.

Other Findings

Beyond weight loss, the Phase 2 trial showed improvements in several metabolic markers:

• Reduced HbA1c (blood sugar control marker)
• Lower triglycerides
• Reduced liver fat
• Improved blood pressure
• Better cholesterol profiles

Retatrutide Dosage Information

Clinical trials have tested several dosage levels of retatrutide. Understanding these protocols helps researchers plan appropriate studies.

Titration Schedule from Clinical Trials

Retatrutide is administered once weekly via subcutaneous injection. Clinical trials used a gradual dose increase (titration) to reduce side effects:

This slow increase allows the body to adjust to the medication and reduces the severity of gastrointestinal side effects. Jumping straight to higher doses increases nausea and vomiting.

Dosage Comparison Table

Reconstitution for Research

Research-grade retatrutide typically comes as a lyophilised (freeze-dried) powder that requires reconstitution before use.

Common reconstitution volumes are 2ml of bacteriostatic water per vial. This creates a solution where each 0.1ml contains a specific dose based on the vial content.

Always refer to specific product documentation for exact reconstitution instructions.

Retatrutide vs Tirzepatide vs Semaglutide

These three peptides are often compared because they all target incretin pathways. Here's how they differ:

Key Differences Explained

Mechanism: Retatrutide's addition of glucagon receptor activation sets it apart. This third target may increase calorie burning and fat breakdown beyond what GLP-1 and GIP can achieve alone.

Weight loss: In head-to-head terms, retatrutide produced 24% average weight loss in 48 weeks, while tirzepatide achieved 22% in 72 weeks and semaglutide achieved 15% in 68 weeks. Retatrutide achieved more weight loss in less time.

Approval status: Semaglutide and tirzepatide are already approved and available on prescription in the UK. Retatrutide is still in clinical trials and not yet approved anywhere in the world.

Side effects: All three peptides share similar gastrointestinal side effects (nausea, vomiting, diarrhoea). The rates appear comparable across trials, though direct comparison studies haven't been published yet.

Side Effects and Safety Considerations

Retatrutide's side effect profile is similar to other incretin-based peptides. Most side effects are gastrointestinal and tend to reduce over time.

Common Side Effects (from Phase 2 trials)

Gastrointestinal effects:

• Nausea (most common, especially during dose increases)
• Diarrhoea
• Vomiting
• Constipation
• Abdominal discomfort

These effects are typically mild to moderate and improve as the body adjusts. Slow dose titration helps reduce their severity.

Other reported effects:

• Decreased appetite (often considered a desired effect)
• Injection site reactions
• Fatigue
• Dizziness

Serious Adverse Events

Serious side effects were uncommon in clinical trials but have been reported with similar peptides:

• Pancreatitis: Inflammation of the pancreas. Symptoms include severe abdominal pain. This is rare but requires immediate medical attention.
• Gallbladder problems: Rapid weight loss can increase the risk of gallstones.
• Hypoglycaemia: Low blood sugar, primarily a concern when combined with other diabetes medications.

Who Should Avoid Retatrutide

Based on clinical trial exclusion criteria and class warnings for similar drugs:

• People with a personal or family history of medullary thyroid carcinoma
• People with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Those with a history of pancreatitis
• Pregnant or breastfeeding women
• People with severe gastrointestinal disease

Storage and Handling

Proper storage is essential for maintaining peptide stability and effectiveness.

Handling Tips

• Allow vials to reach room temperature before reconstituting
• Use bacteriostatic water for reconstitution (contains preservative)
• Add water slowly to avoid damaging the peptide
• Never shake vigorously – gentle swirling only
• Use sterile technique throughout

UK Availability and Regulatory Status

Retatrutide is not currently approved for use in the UK or anywhere else in the world. It remains an investigational compound undergoing clinical trials.

Current Status

• MHRA approval: Not submitted yet
• FDA approval: Not submitted yet
• EMA approval: Not submitted yet
• Clinical trials: Phase 3 ongoing

Expected Timeline

Based on typical drug development timelines:

• Phase 3 completion: 2026-2027
• Regulatory submission: 2027
• Potential approval: 2027-2028
• NHS availability: Would require additional NICE review after MHRA approval

These dates are estimates and subject to change based on trial results and regulatory processes.

Research Peptide Availability

Retatrutide is available from research peptide suppliers for laboratory and in-vitro research purposes. These products are not approved for human use and must be labelled accordingly.

Frequently Asked Questions

Summary

Retatrutide represents a new approach to metabolic research by targeting three hormone receptors instead of one or two. Early clinical trial data suggests it may produce greater weight loss than existing approved medications like tirzepatide and semaglutide.

For researchers interested in studying this compound, it's available through research peptide suppliers for laboratory purposes only.