Skip to content
ContentLora

    Tip: press / anywhere to search.

    product

    Retatrutide

    Also known as LY3437943

    Retatrutide is an investigational weekly injection from Eli Lilly that activates three hormone receptors: GIP, GLP-1 and glucagon.[1] In the peer-reviewed phase 3 TRIUMPH-1 trial the top dose produced a mean 25.0% weight loss at 80 weeks by intention-to-treat (28.3% in Lilly's efficacy analysis). Lilly plans to file it with the FDA in early 2027.[2][3]

    Editor reviewedStrict sourcingUpdated GLP-1 and metabolic medicineHealth and medicineLife sciences
    Key facts

    Retatrutide is a “triple agonist” and the next step in eli-lilly‘s strategy of building more receptor activity into a single molecule.[1] tirzepatide activates the GIP and GLP-1 receptors. Retatrutide adds the glucagon receptor.[4][1] As of October 2026 it is still investigational, with full phase 3 results now published for people with and without type 2 diabetes.[2][5]

    Phase 2

    In a 2023 phase 2 trial of 338 adults with obesity or overweight, retatrutide produced dose-dependent weight loss. At 48 weeks the 12 mg group lost a mean 24.2%, versus 2.1% on placebo.[6] Gastrointestinal adverse events were the most common and were dose-related.[6]

    Phase 3: TRIUMPH

    On 21 May 2026 Lilly reported topline results from TRIUMPH-1. The trial randomised 2,339 adults with obesity or overweight plus a weight-related condition, without diabetes. Lilly said participants on 12 mg lost an average 28.3% of body weight at 80 weeks, and 45.3% of them lost 30% or more.[7] Its release gave 25.9% at 9 mg and 19.0% at 4 mg, and an average 30.3% at 104 weeks in a pre-specified extension of 532 participants with a starting BMI of 35 or more.[8] Discontinuations due to adverse events were 11.3% at 12 mg versus 4.9% on placebo.[9]

    The full results appeared in the New England Journal of Medicine on 29 September 2026. Under the paper’s primary treatment-regimen (intention-to-treat) estimand, which counts everyone randomised whether or not they kept taking the drug, mean weight change at 80 weeks was -17.6%, -23.7% and -25.0% at 4, 9 and 12 mg, versus -3.9% with placebo.[2] Lilly’s May figures came from an efficacy estimand, which estimates the effect in people who stay on treatment, so they are higher.[2] TRIUMPH-1 also showed less knee pain in 574 participants with knee osteoarthritis and fewer breathing interruptions in 243 participants with obstructive sleep apnea.[10]

    TRIUMPH-2, published in The Lancet the same week, enrolled 1,152 adults with obesity and type 2 diabetes. Mean weight change at 80 weeks was -11.9%, -16.8% and -18.8% across the three doses, versus -5.1% with placebo.[5] Weight loss was smaller than in TRIUMPH-1, which excluded people with diabetes.[5][2]

    Safety signals

    Gastrointestinal effects were the most common adverse events in both trials.[2][5] TRIUMPH-2 also reported more hypotension and dysesthesia, an abnormal skin sensation, with retatrutide than with placebo. Permanent discontinuation for adverse events or death was 12% at 9 mg and 8% at 12 mg, versus 5% on placebo.[11] Regulators will judge these signals when Lilly files.[3]

    Regulatory path and grey market

    By August 2026 Lilly reported positive data from three more phase 3 obesity trials. It said the data package was complete for obesity, obstructive sleep apnea and knee osteoarthritis pain, and that it plans to file in the first quarter of 2027.[3] Meanwhile retatrutide is sold illegally online. In August 2026 Lilly stressed that no retatrutide medicine was approved anywhere, filed six lawsuits against US sellers, and said it had reported more than 14,000 websites, adverts and listings.[12]

    Where it fits

    If approved, retatrutide would compete at the high-efficacy end of the market. Novo Nordisk’s cagrisema, another high-efficacy candidate, was under FDA review in late 2026.[13] Trial weight-loss figures are not directly comparable across programmes, because populations, durations and statistical estimands differ.[14][2] For how triple agonism works, see how GLP-1 drugs work.

    Questions readers ask

    Is retatrutide approved?

    No. As of October 2026 it is investigational. Lilly plans to submit a Biologics License Application to the FDA in the first quarter of 2027.[1][3]

    What makes retatrutide a "triple agonist"?

    It activates three receptors, GIP, GLP-1 and glucagon. Tirzepatide activates two and semaglutide one.[1][4]

    What side effects were seen in trials?

    In TRIUMPH-1 the most common adverse events were nausea, diarrhoea, constipation and vomiting. At the 12 mg dose, 11.3% of participants stopped because of adverse events, versus 4.9% on placebo.[9]

    Why do different retatrutide weight-loss figures circulate?

    Lilly's May 2026 topline used an efficacy estimand (28.3% at 12 mg), which assumes people stayed on treatment. The NEJM paper's primary treatment-regimen estimand counts everyone randomised and gives 25.0% versus 3.9% on placebo.[2]

    Can people buy retatrutide now?

    No retatrutide medicine is approved anywhere. Lilly says products sold online are illegal and unverified, and it has sued sellers.[12]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      Retatrutide is an investigational agonist of three receptors, GIP, GLP-1 and glucagon. confirmedas of 2026-10-10

    2. [2]

      The peer-reviewed TRIUMPH-1 report (NEJM, 29 September 2026) gave mean weight changes at 80 weeks of -17.6%, -23.7% and -25.0% with retatrutide 4, 9 and 12 mg versus -3.9% with placebo under the treatment-regimen (intention-to-treat) estimand; Lilly's May topline figures of 19.0%, 25.9% and 28.3% used the efficacy estimand. confirmedas of 2026-09-29

    3. [3]

      As of August 2026, Lilly said three additional phase 3 retatrutide obesity trials were positive, that the data package was complete for obesity, obstructive sleep apnea and knee osteoarthritis pain, and that it plans to submit a Biologics License Application to the FDA in the first quarter of 2027. confirmedas of 2026-08-05

    4. [4]

      Tirzepatide is a single molecule that activates both the GIP and GLP-1 receptors. confirmedas of 2026-10-10

    5. [5]

      In the phase 3 TRIUMPH-2 trial of 1,152 adults with obesity and type 2 diabetes (The Lancet, September 2026), mean weight change at 80 weeks was -11.9%, -16.8% and -18.8% with retatrutide 4, 9 and 12 mg versus -5.1% with placebo; gastrointestinal events were the most common adverse events. confirmedas of 2026-09-29

    6. [6]

      In a 2023 phase 2 trial of 338 adults, retatrutide 12 mg produced a mean 24.2% weight loss at 48 weeks versus 2.1% with placebo; the most common adverse events were gastrointestinal and dose-related. confirmedas of 2023-06-26

    7. [7]

      Lilly reported on 21 May 2026 that in the phase 3 TRIUMPH-1 trial of 2,339 adults with obesity or overweight without diabetes, retatrutide 12 mg produced an average 28.3% weight loss at 80 weeks. confirmedas of 2026-05-21

    8. [8]

      In TRIUMPH-1, average weight loss at 80 weeks was 25.9% at 9 mg and 19.0% at 4 mg of retatrutide, and in a pre-specified 104-week extension of 532 participants with baseline BMI of 35 or more, the 12 mg group lost an average 30.3%. reportedas of 2026-05-21

    9. [9]

      In TRIUMPH-1, discontinuation due to adverse events was 11.3% at the 12 mg retatrutide dose versus 4.9% with placebo; the most common adverse events were gastrointestinal. confirmedas of 2026-05-21

    10. [10]

      In TRIUMPH-1, retatrutide also reduced knee osteoarthritis pain in 574 participants with the condition and reduced apnea-hypopnea events in 243 participants with obstructive sleep apnea, compared with placebo. confirmedas of 2026-09-29

    11. [11]

      In TRIUMPH-2, hypotension and dysesthesia (abnormal skin sensations) were more frequent with retatrutide than placebo, and permanent discontinuation for adverse events or death was 12% at 9 mg and 8% at 12 mg versus 5% with placebo. confirmedas of 2026-09-29

    12. [12]

      In August 2026 Lilly said no retatrutide medicine had been approved anywhere, filed six lawsuits against US sellers of black-market retatrutide and said it had reported more than 14,000 websites, ads and listings marketing it illegally. confirmedas of 2026-08-12

    13. [13]

      Novo Nordisk submitted CagriSema to the US FDA in December 2025 based on REDEFINE 1 and 2, with a decision anticipated by late 2026. confirmedas of 2026-09-21

    14. [14]

      On 23 February 2026 Novo Nordisk reported that CagriSema failed to show non-inferiority to tirzepatide 15 mg in the open-label REDEFINE 4 trial, with weight loss of 20.2% versus 23.6% at 84 weeks under the treatment-regimen estimand. confirmedas of 2026-02-23

    Revision history (2)
    1. Page created.
    2. Refresh: added peer-reviewed TRIUMPH-1 (NEJM) and TRIUMPH-2 (Lancet) results, the estimand difference behind the 28.3% topline, knee-osteoarthritis and sleep-apnea outcomes, and Lilly's action against black-market retatrutide.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "Retatrutide." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/retatrutide

    Spotted an error? Suggest a correction or emailcorrections@contentlora.com.

    Keep exploring

    Connections
    Eli Lilly and Compa… Developed byTirzepatide Adds glucagon receptor to…CagriSema Rival next-generation can…
    ☰ Contents