What is retatrutide and how does it work?

Retatrutide is a triple agonist peptide that targets GLP-1, GIP, and glucagon receptors simultaneously. It suppresses appetite and slows gastric emptying (via GLP-1), improves insulin sensitivity and lipid metabolism (via GIP), and increases energy expenditure and liver fat oxidation (via glucagon). This three-pronged mechanism produced up to 24.2% weight loss in phase 2 trials.

When will retatrutide be FDA-approved?

Retatrutide is currently in phase 3 clinical trials. Data readouts are expected in late 2026 to early 2027. If results are positive, FDA submission could come in 2027 with potential approval in 2028. However, regulatory timelines are uncertain and dependent on trial outcomes and safety data.

How does retatrutide compare to tirzepatide?

Retatrutide produced 24.2% weight loss in phase 2 vs tirzepatide's 22.5% in phase 3 (SURMOUNT-1). The key difference is retatrutide's glucagon receptor component, which increases energy expenditure — an effect neither semaglutide nor tirzepatide provides. Phase 3 data will determine how the two compare in larger populations.

Phase 2 trial data showed a safety profile similar to other GLP-1 medications — primarily gastrointestinal side effects (nausea, diarrhea) that were most common during dose escalation. Phase 3 trials involving thousands of participants will provide more comprehensive safety data. The glucagon component is a novel element whose long-term safety profile is still being established.

Can I get retatrutide now?

Retatrutide is not yet approved or commercially available. It is only accessible through enrollment in clinical trials. Research-grade versions may be available from peptide research suppliers, but these are unregulated and sold for research use only. The approved commercial version is at least 2 years away.

Retatrutide Phase 3 Results: What We Know So Far (2026)

What Is Retatrutide?

Retatrutide (LY3437943) is a first-in-class triple agonist peptide developed by Eli Lilly that targets three receptors simultaneously: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon. This triple mechanism distinguishes it from semaglutide (GLP-1 only) and tirzepatide (GLP-1 + GIP), positioning retatrutide as potentially the most effective weight loss peptide in development.^[1]

The addition of glucagon receptor agonism is the key innovation. Glucagon increases energy expenditure, promotes hepatic fat oxidation, and reduces liver fat — effects that complement the appetite suppression and metabolic improvements delivered by GLP-1 and GIP activation. For background on how GLP-1 agonists work, see our GLP-1 Guide.

Phase 2 Results: Record-Breaking Weight Loss

The phase 2 trial of retatrutide, published in the New England Journal of Medicine in 2023, produced the highest weight loss ever reported for any obesity medication:

12 mg dose: 24.2% mean body weight loss at 48 weeks (compared to 2.1% with placebo)
8 mg dose: 22.8% weight loss
4 mg dose: 17.1% weight loss
Participants losing >25% body weight: Over 50% at the 12 mg dose

These numbers exceeded tirzepatide's SURMOUNT-1 results (22.5% at 15 mg over 72 weeks) despite a shorter treatment period. Importantly, the weight loss curves had not fully plateaued at 48 weeks, suggesting even greater reductions with longer treatment.^[1]

The Phase 3 Program: What We Know

Eli Lilly launched the phase 3 TRIUMPH program for retatrutide in late 2023. As of early 2026, the program includes multiple trials:

TRIUMPH-1: Retatrutide for adults with obesity or overweight with at least one weight-related comorbidity. This is the registration trial that will likely form the basis of FDA submission.
TRIUMPH-2: Retatrutide in adults with type 2 diabetes, evaluating both glycemic control and weight loss.
TRIUMPH-3: Retatrutide for MASH (metabolic dysfunction-associated steatohepatitis, formerly NASH). The glucagon receptor component is particularly relevant here, as glucagon drives hepatic fat oxidation.
TRIUMPH-4: Retatrutide in adolescents with obesity.

Phase 3 trials typically enroll larger populations (3,000-5,000+ participants) and run for 52-76 weeks. The primary endpoints will include percent change in body weight, proportion of participants achieving clinically meaningful weight loss thresholds (5%, 10%, 15%, 20%), and safety/tolerability.

The Triple Agonist Advantage

Understanding why three receptors outperform two requires looking at what each contributes:

Receptor	Primary Effects	Compound Targeting It
GLP-1	Appetite suppression, slowed gastric emptying, insulin secretion	Semaglutide, tirzepatide, retatrutide
GIP	Enhanced insulin sensitivity, lipid metabolism, potential nausea reduction	Tirzepatide, retatrutide
Glucagon	Increased energy expenditure, hepatic fat oxidation, liver fat reduction	Retatrutide only

The glucagon component is what separates retatrutide from the current generation. While GLP-1 and GIP reduce caloric intake, glucagon increases caloric expenditure — attacking the energy balance equation from both sides simultaneously. This may explain why retatrutide achieves weight loss approaching surgical outcomes without the irreversibility of bariatric surgery.

For detailed comparisons, see our retatrutide vs tirzepatide and retatrutide vs semaglutide analysis pages.

Safety and Side Effects

In the phase 2 trial, retatrutide's side effect profile was broadly similar to other GLP-1-based therapies:

Gastrointestinal: Nausea (25-35%), diarrhea (20-25%), vomiting (10-15%), constipation (10-15%) — comparable to tirzepatide and somewhat less than semaglutide
Dose-dependent: Side effects were most common during dose escalation and decreased with continued use
Discontinuation rate: 6-10% due to adverse events, consistent with other GLP-1 agonists
Heart rate: Small increases in heart rate were observed (1-3 bpm), consistent with the glucagon component increasing metabolic rate

The phase 3 trials will provide critical data on rare adverse events (pancreatitis, gallbladder disease, thyroid tumors) that require larger sample sizes to characterize accurately. The glucagon receptor component also raises theoretical concerns about blood glucose elevation in fasting states, though the phase 2 data showed improved glycemic control overall.

Projected Timeline and Approval

Based on publicly available information from Eli Lilly:

Phase 3 enrollment: Completed through 2024-2025
Phase 3 data readout: Expected late 2026 to early 2027
FDA submission: Likely 2027, contingent on positive phase 3 results
Potential approval: 2028 at the earliest, assuming standard FDA review timeline

Lilly has stated that retatrutide is a high priority in their obesity pipeline. Given the company's track record with tirzepatide (which moved from phase 3 to approval in approximately 18 months), the timeline could be accelerated if the data is strong. However, regulatory timelines are inherently uncertain, and any safety signal could delay the process significantly.

What This Means for the Obesity Treatment Landscape

If retatrutide's phase 3 data confirms the phase 2 results, it would represent a step-change in medical obesity treatment. Weight loss approaching 25-30% bridges the gap between pharmacotherapy and bariatric surgery (which typically produces 25-35% weight loss). This could fundamentally alter the treatment algorithm for severe obesity.

The competitive landscape is also evolving. Survodutide (Boehringer Ingelheim's GLP-1/glucagon dual agonist) and CagriSema (Novo Nordisk's cagrilintide + semaglutide combination) are also in late-stage development. See our weight loss goal page for a comprehensive view of all compounds in this space.