Retatrutide is an investigational peptide being studied for obesity, type 2 diabetes and several related metabolic conditions. Unlike compounds that target only the GLP-1 receptor, retatrutide activates three hormone receptors at once: GIP, GLP-1 and glucagon.

Clinical trials have reported substantial effects on body weight and blood glucose, while more recent Phase 3 research has also examined outcomes including knee osteoarthritis pain and obstructive sleep apnoea.

The evidence has developed quickly. Early Phase 2 results published in the New England Journal of Medicine established a strong clinical signal, and multiple Phase 3 trials reported or published in 2026 have considerably expanded the evidence base.

Retatrutide remains investigational and is not approved by the Therapeutic Goods Administration (TGA) in Australia for therapeutic use. 

What Is Retatrutide?

Retatrutide, also known by the development code LY3437943, is a single molecule developed by Eli Lilly.

It is described as a triple hormone receptor agonist because it activates three receptors:

• glucose-dependent insulinotropic polypeptide (GIP)
• glucagon-like peptide-1 (GLP-1)
• glucagon

This distinguishes retatrutide from single-receptor GLP-1 compounds and dual GIP and GLP-1 receptor agonists.

The term “reta peptide” is also sometimes used informally online when referring to retatrutide. People searching for what reta peptide does are generally asking about the same investigational compound and its three-receptor mechanism.

How Does Retatrutide Work?

Retatrutide has attracted scientific interest because the three receptors it activates are involved in different but overlapping aspects of metabolism and energy regulation.

GLP-1 Receptor

GLP-1 is an incretin hormone involved in glucose-dependent insulin secretion, appetite signalling and gastric emptying.

Activation of this pathway is already well established in metabolic research.

GIP Receptor

GIP is another incretin hormone involved in glucose-dependent insulin signalling and metabolic regulation.

Combining GIP and GLP-1 activity is already an established area of research. Retatrutide adds a third receptor pathway to that combination.

Glucagon Receptor

Glucagon has a different metabolic role and is involved in hepatic glucose regulation and energy metabolism.

Adding glucagon receptor agonism is one of the main features that distinguishes retatrutide from earlier incretin-based compounds.

Current human studies show the effects of the complete molecule. They do not allow every observed clinical outcome to be cleanly attributed to one individual receptor.

What Does Retatrutide Do According to Clinical Trials?

The strongest human evidence currently comes from studies investigating obesity and type 2 diabetes.

The clinical program has progressed from Phase 2 studies into several large Phase 3 trials.

The distinction between these evidence types matters. Peer-reviewed studies have undergone formal scientific review and generally provide substantially more detail than company-issued topline results.

What Did the Phase 2 Obesity Trial Show?

One of the studies that brought retatrutide widespread scientific attention was a Phase 2 trial published in the New England Journal of Medicine in 2023.

The randomised, double-blind, placebo-controlled trial involved 338 adults with obesity, or overweight plus at least one weight-related condition.

At 48 weeks, mean body-weight changes were:

• 8.7% reduction in the 1 mg group
• 17.1% reduction across the combined 4 mg groups
• 22.8% reduction across the combined 8 mg groups
• 24.2% reduction in the 12 mg group
• 2.1% reduction with placebo

The most commonly reported adverse events were gastrointestinal and were generally mild to moderate. Researchers also reported dose-dependent increases in heart rate, which peaked during the trial and subsequently declined. We examine the retatrutide side effects reported across the Phase 2 and Phase 3 trials separately, including how they vary by dose and what remains unknown.

The study established a strong clinical signal, but it involved several hundred participants. Larger Phase 3 trials were needed to determine whether those findings would hold across broader populations.

Read the peer-reviewed Phase 2 study in the New England Journal of Medicine.

What Do the Latest Phase 3 Retatrutide Trials Show?

The evidence base expanded significantly in 2026, with several Phase 3 studies either producing peer-reviewed results or having topline findings announced by Lilly.

The Phase 3 evidence also includes TRANSCEND-T2D-2, a head-to-head trial comparing retatrutide with semaglutide. Our ⁠retatrutide vs Ozempic analysis examines the reported differences in weight loss, blood sugar control and adverse events.

TRIUMPH-1

TRIUMPH-1 studied more than 2,300 participants with obesity or overweight and at least one weight-related condition, without type 2 diabetes.

Lilly reported in May 2026 that participants receiving 12 mg retatrutide had an average body-weight reduction of 28.3% after 80 weeks. The company also reported that 45.3% of participants in that group lost at least 30% of their starting body weight.

An extension involving participants who began with a BMI of at least 35 reported an average reduction of 30.3% at 104 weeks.

These figures were initially released as company-reported Phase 3 topline results. The complete TRIUMPH-1 results were subsequently published in the New England Journal of Medicine on 29 September 2026.

See Lilly’s published TRIUMPH-1 topline results.

TRANSCEND-T2D-1

The evidence for type 2 diabetes became stronger in June 2026 when results from the Phase 3 TRANSCEND-T2D-1 trial were published in The Lancet.

The randomised, double-blind trial involved 537 adults whose type 2 diabetes was inadequately controlled with diet and exercise.

After 40 weeks, retatrutide produced greater reductions in HbA1c than placebo across the studied groups. Body weight was also reduced, with the largest mean reduction reported in the 12 mg group.

This provides peer-reviewed Phase 3 evidence that retatrutide can affect both glycaemic control and body weight in the population studied. 

Read the peer-reviewed TRANSCEND-T2D-1 study published in The Lancet.

TRIUMPH-2 and TRIUMPH-3

In July 2026, Lilly announced topline results from two further Phase 3 studies.

TRIUMPH-2 studied 1,152 adults with type 2 diabetes and obesity or overweight. Lilly reported mean body-weight reductions of up to 20.8% at 80 weeks, along with reductions in HbA1c.

TRIUMPH-3 involved 1,949 participants with severe obesity and established cardiovascular disease. Participants receiving the highest studied dose had a reported average body-weight reduction of 22.6% at 80 weeks.

The cardiovascular findings require careful interpretation.

TRIUMPH-3 reported improvements in several cardiovascular risk markers, including triglycerides, blood pressure and waist circumference. However, the study did not establish that retatrutide reduces major cardiovascular events such as cardiovascular death, heart attack or stroke.

Improvement in cardiovascular risk factors is not the same as demonstrating fewer cardiovascular events. 

See Lilly’s TRIUMPH-2 and TRIUMPH-3 topline results.

What Else Is Retatrutide Being Studied For?

The retatrutide research program now extends beyond body weight and blood glucose.

TRIUMPH-1 included participant groups with knee osteoarthritis and moderate-to-severe obstructive sleep apnoea.

Lilly reported reductions of up to 73.1% in knee osteoarthritis pain and up to 60.6% in obstructive sleep apnoea severity in the relevant study populations. 

These findings do not mean retatrutide should simply be described as a treatment for either condition. They show that researchers are examining whether broader metabolic changes associated with retatrutide translate into measurable improvements in obesity-related complications.

Current or planned research has also examined or is examining:

• cardiovascular and kidney outcomes
• chronic low back pain
• weight maintenance
• metabolic dysfunction-associated steatotic liver disease
• obesity and overweight with additional metabolic conditions

The answer to “what does retatrutide do?” is therefore becoming broader as the clinical program develops.

What Does the Research Not Tell Us Yet?

The headline results are notable, but important questions remain unresolved.

Long-Term Cardiovascular Outcomes

Changes in blood pressure, lipids or other cardiovascular risk markers do not automatically establish protection against cardiovascular events.

A dedicated outcomes trial is evaluating cardiovascular and kidney endpoints in a much larger population. Until that evidence is available, claims about cardiovascular protection would go beyond what the current evidence supports.

Long-Term Safety

Retatrutide has now been studied in thousands of participants, but it remains investigational. Our analysis of whether retatrutide is safe looks at the Phase 2 and Phase 3 safety evidence in more detail, including serious adverse events and what remains unknown.

Safety evidence will continue to develop through longer trials, larger populations and regulatory review.

Durability of the Observed Effects

Longer-term evidence is also needed to determine how durable the observed changes are over several years and what happens when treatment is changed or discontinued.

The Contribution of Each Receptor

Retatrutide activates GIP, GLP-1 and glucagon receptors simultaneously.

Clinical studies tell researchers what happens when the complete molecule is used, but they do not allow each outcome to be cleanly assigned to an individual receptor pathway.

Is Retatrutide Approved in Australia?

No.

As of August 2026, retatrutide remains investigational and is not included in the Australian Register of Therapeutic Goods as an approved therapeutic product. Our analysis of whether retatrutide is available in Australia explains the current TGA status and Australian availability in more detail.

The Therapeutic Goods Administration has specifically identified retatrutide among unapproved peptide products being promoted and supplied in Australia.  

In June 2026, the TGA and Australia’s Chief Medical Officer issued a joint statement warning about the growing availability and use of unapproved peptide products. The TGA states that products not included in the ARTG have not been evaluated by the regulator for therapeutic safety, quality or effectiveness. 

The regulator has also made clear that describing a peptide as “research use only” does not, by itself, change its regulatory status or remove applicable importation, advertising or supply obligations.

This regulatory status is separate from the clinical research described throughout this article.

Retatrutide Research in Australia

Australia has participated directly in retatrutide clinical research.

The Phase 3 TRIUMPH-1 study included Australian research locations in New South Wales, Queensland, South Australia and Victoria.

For information on research-only supply, batch documentation and account access in Australia, see our Retatrutide Australia page.

Research, possession, importation and supply of peptide products in Australia remain subject to applicable Commonwealth, state and territory requirements.  

Key Takeaways

Retatrutide is an investigational triple hormone receptor agonist that activates GIP, GLP-1 and glucagon receptors in a single molecule.

Clinical research has reported substantial effects on body weight, while peer-reviewed Phase 3 evidence also shows effects on glycaemic control in people with type 2 diabetes.

More recent Phase 3 programs are examining a broader range of outcomes, including knee osteoarthritis pain, obstructive sleep apnoea and cardiovascular and kidney outcomes.

Important questions remain around long-term safety, durability and cardiovascular outcomes.

Retatrutide remains investigational and is not currently approved by the TGA for therapeutic use in Australia.

Research Sources

Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine, 2023.

Bajaj HS, et al. Efficacy and Safety of Retatrutide in People With Type 2 Diabetes and Inadequate Glycaemic Control With Diet and Exercise TRANSCEND-T2D-1. The Lancet, 2026.

ClinicalTrials.gov TRIUMPH-1, NCT05929066.

Eli Lilly and Company TRIUMPH-1 Phase 3 Topline Results, May 2026.

Eli Lilly and Company TRIUMPH-1 Additional Obesity, Osteoarthritis and Obstructive Sleep Apnoea Findings, June 2026.

Eli Lilly and Company TRIUMPH-2 and TRIUMPH-3 Phase 3 Topline Results, July 2026.

ClinicalTrials.gov TRIUMPH-Outcomes, NCT06383390.

Therapeutic Goods Administration Understanding Your Responsibilities When Importing, Compounding and Supplying Unapproved Peptide Products, April 2026.

Therapeutic Goods Administration and Australian Chief Medical Officer Concerns Regarding the Public Health Risks Associated With Unapproved Peptide Products, June 2026.