Retatrutide Phase 2 Trial Results: What the NEJM Study Actually Found

Retatrutide has generated substantial scientific and public interest following clinical trials investigating its potential use in obesity. The first major published human study was a Phase 2 randomised, placebo-controlled trial published in the New England Journal of Medicine in 2023 (Jastreboff et al., 2023).

The study reported substantial reductions in body weight over 48 weeks, particularly at the higher investigational doses, while also documenting gastrointestinal adverse events, treatment discontinuations, and dose-related increases in heart rate (Jastreboff et al., 2023).

Importantly, this was a clinical trial of an investigational pharmaceutical compound under controlled research conditions. It should not be confused with products sold online or through other unregulated channels under the name “retatrutide” (Jastreboff et al., 2023; TGA, 2026a).

What Is Retatrutide?

Retatrutide, also known by the development code LY3437943, is an investigational triple hormone-receptor agonist that activates the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors (Jastreboff et al., 2023). The Phase 2 study was designed to investigate the dose-response relationship for retatrutide in adults with obesity or overweight who did not have type 2 diabetes (Jastreboff et al., 2023).

How Was the Phase 2 Trial Designed?

The Phase 2 trial enrolled 338 adults with obesity or overweight and without type 2 diabetes (Jastreboff et al., 2023). Participants were randomly assigned to receive placebo or different doses of once-weekly retatrutide — 1mg, 4mg, 8mg, or 12mg — for 48 weeks (Jastreboff et al., 2023).

The primary endpoint was the percentage change in body weight from baseline at 24 weeks, while weight change at 48 weeks and predefined weight-loss thresholds were among the secondary outcomes (Jastreboff et al., 2023). Because the study was randomised and placebo-controlled, it provides substantially stronger evidence about the effects observed within the trial than uncontrolled anecdotal reports or laboratory studies. However, a Phase 2 trial remains part of the clinical development process and does not by itself establish long-term safety or regulatory approval.

What Weight Loss Did the Trial Report?

The study found a dose-related reduction in body weight. At 48 weeks, the least-squares mean percentage change in body weight was:

Treatment	Mean change in body weight at 48 weeks
Placebo	−2.1%
Retatrutide 1mg	−8.7%
Retatrutide 4mg	−17.1%
Retatrutide 8mg	−22.8%
Retatrutide 12mg	−24.2%

(Jastreboff et al., 2023)

The researchers also reported that the weight-loss curve had not clearly reached a plateau by the end of the 48-week treatment period (Jastreboff et al., 2023). This does not mean that an individual taking retatrutide would necessarily experience a 24.2% reduction in body weight. The figure is a trial-level least-squares mean result from a specific population, dose, and study period, rather than a prediction for an individual patient.

How Many Participants Reached Different Weight-Loss Thresholds?

The trial also reported the proportion of participants achieving at least 5%, 10%, and 15% weight reduction at 48 weeks. For participants receiving 4mg, 92% achieved at least 5% weight loss, 75% achieved at least 10%, and 60% achieved at least 15% (Jastreboff et al., 2023). For 8mg, the corresponding figures were 100%, 91%, and 75%. For 12mg, they were 100%, 93%, and 83%. For comparison, 27% of participants receiving placebo achieved at least 5% weight loss, 9% achieved at least 10%, and 2% achieved at least 15% (Jastreboff et al., 2023).

These results demonstrate the magnitude of the effects observed in this particular clinical trial, but they should not be interpreted as a guarantee of individual treatment response.

What Side Effects Were Reported?

During the treatment period, adverse events were reported in 70% of participants receiving placebo and in 73% to 94% of participants receiving retatrutide, with the highest rates reported in the 8mg and 12mg groups (Jastreboff et al., 2023).

Gastrointestinal side effects were the most frequently reported adverse events among participants receiving retatrutide — nausea, diarrhoea, vomiting, and constipation, occurring more frequently than with placebo. These events occurred primarily during dose escalation, were predominantly mild to moderate, and were more frequent at higher doses. Gastrointestinal adverse events were partially mitigated when participants began treatment at 2mg rather than 4mg before escalation (Jastreboff et al., 2023).

Discontinuation due to adverse events occurred in 6% to 16% of participants receiving retatrutide, compared with none of the participants receiving placebo, with gastrointestinal events the most common cause (Jastreboff et al., 2023).

Serious adverse events were reported in both treatment and placebo groups, with no clear imbalance across the retatrutide dose groups. Fifteen serious adverse events occurred among 13 participants during the trial, including one case of acute pancreatitis in a participant receiving retatrutide (Jastreboff et al., 2023). The presence of serious adverse events in a clinical trial does not by itself establish that the investigational treatment caused each event — determining causality requires clinical assessment of individual cases and comparison with expected background risk.

Heart rate increased in a dose-dependent manner among participants receiving retatrutide, peaking at approximately 24 weeks before declining during the remainder of the study period (Jastreboff et al., 2023).

Skin sensitivity — cutaneous hyperesthesia, meaning increased sensitivity of the skin — was reported in 7% of participants receiving retatrutide compared with 1% receiving placebo. These events were not classified as severe or serious (Jastreboff et al., 2023).

One death occurred during the trial. An external committee reviewing the case was unable to determine whether it was cardiovascular-related, and the event was adjudicated as undetermined. No participant experienced clinically significant hypoglycaemia during the treatment period (Jastreboff et al., 2023).

What Does This Phase 2 Study Actually Prove?

The results provide evidence that retatrutide produced substantial weight reduction in the population studied over 48 weeks (Jastreboff et al., 2023). The randomised, placebo-controlled design provides a stronger basis for evaluating treatment effects than uncontrolled reports or anecdotal experiences.

However, the study does not establish the long-term safety of retatrutide beyond the period studied. It also does not establish how every individual will respond to treatment, nor does it establish the safety or composition of products sold outside the controlled clinical-trial environment. These distinctions matter because the TGA has warned that unapproved peptide products may not have been evaluated for safety, quality, or effectiveness, and may contain inaccurate amounts of active ingredients, undisclosed substances, or contaminants (TGA, 2026a).

Phase 2 Was Not the End of the Research

Since the 2023 Phase 2 publication, retatrutide has progressed into multiple Phase 3 clinical trials as part of Eli Lilly’s TRIUMPH development programme (Eli Lilly, 2026a). In May 2026, Eli Lilly reported topline results from TRIUMPH-1, a Phase 3 study involving adults with obesity or overweight and at least one weight-related comorbidity who did not have diabetes. The company reported that participants receiving the 12mg dose lost an average of 28.3% of body weight at 80 weeks in that study (Eli Lilly, 2026a).

In July 2026, Eli Lilly announced topline results from two additional Phase 3 trials. TRIUMPH-2, in adults with obesity and type 2 diabetes, reported weight loss of up to 20.8% at 80 weeks on the 12mg dose. TRIUMPH-3, in adults with severe obesity and established cardiovascular disease, reported weight loss of up to 22.6% at 80 weeks on the 12mg dose (Eli Lilly, 2026b). These later Phase 3 findings are relevant to understanding the evolving evidence base, but they do not change the regulatory status of retatrutide in Australia. It’s also worth distinguishing company-reported topline results from final peer-reviewed publications — detailed results from TRIUMPH-2 and TRIUMPH-3 were, as of the announcement, still to be presented at future medical meetings and published in peer-reviewed journals (Eli Lilly, 2026b).

Is Retatrutide Approved in Australia?

No. Retatrutide is not an approved therapeutic good in Australia. The TGA identifies retatrutide among unapproved peptide products and states that unapproved peptide products have not been evaluated by the TGA for safety, quality, or effectiveness (TGA, 2026a). Retatrutide should not be presented to Australian consumers as an approved weight-loss medicine.

What About Retatrutide Products Sold Online?

This is where the distinction between the clinical trial compound and products sold online becomes particularly important. The Phase 2 study investigated a controlled pharmaceutical product supplied within a clinical research environment (Jastreboff et al., 2023). A product purchased online under the name “retatrutide” is not automatically equivalent to the investigational product studied in that trial.

The TGA has warned that unapproved peptide products may have unknown or inaccurate contents, may be poorly labelled, may contain different amounts of active ingredient than stated, and may present risks including contamination and infection, particularly when supplied as injectable products (TGA, 2026a). In June 2026, the TGA and Australia’s Chief Medical Officer also reported serious adverse effects associated with unapproved peptide products, including liver damage and severe allergic reactions requiring hospitalisation (TGA, 2026b). The TGA subsequently reported that retatrutide was among illicit peptide products seized during an enforcement operation in New South Wales in August 2026 (TGA, 2026c).

For this reason, the results of a legitimate clinical trial should never be used as evidence that an unapproved product purchased online is safe, accurately manufactured, or equivalent to the investigational product studied by researchers.

What Does This Mean for Australian Consumers?

The clinical evidence for retatrutide is evolving, and the Phase 2 study provides important information about both its potential effects and its adverse-event profile. At the same time, retatrutide remains an investigational, unapproved therapeutic good in Australia, and the TGA continues to warn about the risks associated with unapproved peptide products (TGA, 2026a).

The appropriate conclusion is therefore not that the Phase 2 results make retatrutide an available Australian treatment. Rather, the trial demonstrates why retatrutide is being investigated as a potential future medicine, while the regulatory and safety questions surrounding its use outside approved clinical pathways remain important.

The Bottom Line

The 2023 NEJM Phase 2 trial found substantial, dose-dependent reductions in body weight among adults with obesity or overweight without type 2 diabetes who received retatrutide for 48 weeks — but also documented gastrointestinal adverse events, treatment discontinuations, and dose-related increases in heart rate, demonstrating that the investigational treatment was not without adverse effects (Jastreboff et al., 2023).

Retatrutide has since progressed into Phase 3 development, with additional results reported in 2026, although the medicine remains investigational and has not been approved by the TGA in Australia (Eli Lilly, 2026a; TGA, 2026a). Most importantly, evidence from a controlled clinical trial of pharmaceutical-grade investigational retatrutide should not be extrapolated to products sold online under the same name.

GL Vitality Drips does not coordinate access to retatrutide.

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References

1. Eli Lilly (2026a) Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial, 21 May. View the Healio report on the TRIUMPH-1 topline results (Accessed: 30 August 2026).
2. Eli Lilly (2026b) Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C, 23 July. View the Eli Lilly investor announcement on TRIUMPH-2 and TRIUMPH-3 (Accessed: 30 August 2026).
3. Jastreboff, A.M., Kaplan, L.M., Frías, J.P., Wu, Q., Du, Y., Gurbuz, S., Coskun, T., Haupt, A., Milicevic, Z. and Hartman, M.L. (2023) ‘Triple–hormone-receptor agonist retatrutide for obesity — A phase 2 trial’, New England Journal of Medicine, 389(6), pp. 514–526. View the full article in the New England Journal of Medicine (Accessed: 30 August 2026).
4. Therapeutic Goods Administration (2026a) Understanding your responsibilities when importing, compounding and supplying unapproved peptide products, 13 April. View the TGA safety alert on unapproved peptide products (Accessed: 30 August 2026).
5. Therapeutic Goods Administration (2026b) Concerns regarding the public health risks associated with unapproved peptide products, 19 June. View the TGA media release on public health risks (Accessed: 30 August 2026).
6. Therapeutic Goods Administration (2026c) TGA flexes its muscle against illegal peptides and steroids, 17 August. View the TGA media release on the NSW enforcement operation (Accessed: 30 August 2026).

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