Retatrutide: US compassionate use explained

On 7 August 2026, the BMJ reported that retatrutide, Eli Lilly's triple GLP-1/GIP/glucagon receptor agonist, has opened to compassionate use in the United States^[1]. The timing followed public speculation that US President Donald Trump had been taking the drug. Retatrutide has not been approved by the FDA for any indication, but the compassionate use pathway under US law allows patients with serious or life-threatening conditions to access investigational medicines outside of clinical trials in certain circumstances.

What compassionate use means under US law

Compassionate use is the informal name for what the FDA formally calls expanded access. Under 21 CFR Part 312, Subpart I, a physician can apply on behalf of a patient to use an investigational drug outside a clinical trial when three conditions are met: the patient has a serious or immediately life-threatening condition, no comparable or satisfactory alternative therapy exists, and the potential patient benefit justifies the potential risk^[2]. The FDA grants the large majority of individual-patient requests it receives. In recent years the agency has reported approving more than 98% of emergency applications within 24 hours and more than 95% of non-emergency requests within 30 days.

There are three tiers. Individual patient access is the most common: a single physician applies for a single patient. Intermediate-size population access covers a small group of patients with the same condition. A treatment IND or treatment protocol is the broadest tier and is used when a drug is already in late-stage trials and is likely to be approved.

Where retatrutide stands in its clinical programme

Retatrutide completed TRIUMPH-1, a Phase 3 trial in 2,339 adults with obesity or overweight plus at least one weight-related comorbidity but without type 2 diabetes. The 12 mg weekly dose produced a mean 28.3% body-weight reduction at 80 weeks against 2.2% on placebo^[3]. The 9 mg dose produced 25.9% mean weight loss; the 4 mg dose 19.0%. In a 104-week extension subgroup, the 12 mg dose reached 30.3% mean reduction.

The Phase 2 data published in the New England Journal of Medicine in 2023 showed 24.2% mean body-weight reduction on the 12 mg dose at 48 weeks^[4]. A dose-dependent increase in heart rate was observed, peaking around week 24 and then declining. The dominant adverse events across both Phase 2 and TRIUMPH-1 are gastrointestinal and dose-dependent: nausea, vomiting, diarrhoea, and constipation, consistent with the broader incretin class.

TRIUMPH-1 is not the only Phase 3 readout. TRANSCEND-T2D-1, the type 2 diabetes trial, reported data in March 2026. Additional obesity studies, TRIUMPH-2 and TRIUMPH-3, have primary completion expected later in 2026^[3]. The cardiovascular outcomes trial TRIUMPH-Outcomes (NCT06383390) runs to 2029. Eli Lilly has not publicly stated an FDA submission timeline.

The gap between trial data and approved access

TRIUMPH-1 produced the largest mean weight loss reported in any Phase 3 incretin trial to date, surpassing SURMOUNT-1 for tirzepatide (20.9% at 72 weeks) and STEP-1 for semaglutide (14.9% at 68 weeks). But a topline trial result is not regulatory approval. Regulators review the full dataset, the safety database, the manufacturing specifications, and the proposed label before granting a marketing authorisation. That process takes months after the sponsor files.

Compassionate use fills part of that gap. A physician who has a patient with severe obesity and exhausted other approved options can apply to Eli Lilly for a drug supply and to the FDA for an IND. Both parties must agree. Lilly is under no legal obligation to supply the drug; the company decides whether its manufacturing capacity and the patient's clinical profile warrant participation.

The illicit market context

The compassionate use news sits alongside a parallel problem: a growing illicit and compounded retatrutide market. A July 2026 BMJ fact check by Elisabeth Mahase examined claims that a person had died after using an unapproved product labelled as retatrutide^[5]. A September 2026 analysis of products sold as retatrutide in Australia found labelling and composition inaccuracies, with references to counterfeit products linked to serious health risks including liver failure^[6].

The FDA has since September 2025 sent warning letters to compounding pharmacies selling unauthorised retatrutide. The agency's position is that retatrutide cannot be used in compounding under federal law because it is not on the 503A or 503B bulks list and is not in short supply as an approved product. That is a separate question from the formal expanded access pathway: an individual patient seeking legitimate compassionate use goes through physician and Lilly, not a compounding pharmacy.

What this means for patients now

Retatrutide is not approved. Approved options for obesity in the US include tirzepatide (Zepbound) and semaglutide (Wegovy). A patient who is not eligible for or not responding to approved options, and whose physician believes the Phase 3 evidence supports a trial, may ask their physician to pursue expanded access. There is no guarantee Lilly will agree to supply the drug, and the clinical criteria for serious conditions apply.

Patients should not seek retatrutide outside approved clinical trials or formal expanded access. Products sold on grey markets and compounding pharmacy channels lack the quality controls of the trials, and the risk profile of a mislabelled or contaminated product is categorically different from the risk profile documented in the TRIUMPH programme.

Consult a physician before drawing any conclusions about whether retatrutide would be appropriate in a specific clinical situation. This article describes the regulatory framework, not a treatment protocol.