Retatrutide

The short version

I take retatrutide. As of November 2026 it is investigational and not approved: Lilly, its maker, calls it "an investigational molecule that cannot be legally sold or marketed for human use," and the FDA says it has "not been found safe and effective for any condition"^1,2. Lilly plans to apply for FDA approval in the first quarter of 2027¹.
In the phase 3 TRIUMPH-1 trial of 2,339 adults with obesity and no diabetes, 80 weeks of once-weekly retatrutide cut body weight by 17.6% (4 mg), 23.7% (9 mg), and 25.0% (12 mg), versus 3.9% on placebo³.
In other trials it lowered HbA1c in type 2 diabetes, liver fat, and the severity of sleep apnea^4,5,6.
The most common side effects are gastrointestinal. In TRIUMPH-2, 12% on 9 mg and 8% on 12 mg stopped treatment for adverse events or death, versus 5% on placebo^3,7.
Nobody knows yet what it does to heart attacks and strokes, what happens after stopping, or what years of use look like: heart events in TRIUMPH-3 were too few to show a benefit, and the trials ran 40 to 80 weeks^1,4,3.

How I use it

I take retatrutide. Everything else on this page is what the trials used, not my routine.

Where it stands as of November 2026

Not approved. Lilly's July 23, 2026 press release calls retatrutide "an investigational molecule that cannot be legally sold or marketed for human use"¹. Healio, a medical news site, reported on August 14, 2026 that it had not yet been reviewed by the FDA⁸.
Filing plan. In the same release, Lilly said it is completing the chemistry, manufacturing, and controls data package for a biologics license application and plans to submit it to the FDA in the first quarter of 2027¹. I found no sign of a filing or an approval in the sources I opened as of November 5, 2026.
What the FDA says. The FDA's page on unapproved GLP-1 drugs, current as of October 1, 2026, says retatrutide "cannot be used in compounding under federal law" and that it and cagrilintide have "not been found safe and effective for any condition." It says FDA has warned companies that "have illegally sold unapproved drugs containing semaglutide, tirzepatide, retatrutide, survodutide or mazdutide that are falsely labeled 'for research purposes' or 'not for human consumption,'" and that "the agency urges consumers not to purchase these products which are of unknown quality and may be harmful to their health." It has also warned telehealth companies "for marketing unapproved drugs such as retatrutide"².
Counterfeits. Healio also reported that Lilly had sued six companies it says sell counterfeit, unapproved versions of retatrutide⁸.

The protocol

This is what the trials used, not a prescription and not advice for anyone.

Parameter	What the trials used
Route and schedule	Once-weekly injection under the skin^9,3
Phase 2 doses	1, 4, 8, or 12 mg a week for 48 weeks, with 2 mg and 4 mg starting doses compared^9,5
Phase 3 doses	4, 9, or 12 mg a week for 80 weeks in TRIUMPH-1 and TRIUMPH-2 and for 40 weeks in TRANSCEND-T2D-1; 9 or 12 mg for 80 weeks in TRIUMPH-3^3,7,4,1
Starting dose	In phase 2, starting at 2 mg rather than 4 mg partly eased the gastrointestinal side effects⁹
Who was studied	Adults with obesity or overweight, some with type 2 diabetes, sleep apnea, knee osteoarthritis, or established cardiovascular disease^3,7,6,1

Why it works

Retatrutide activates three hormone receptors: GIP, GLP-1, and glucagon⁹. The abstracts and pages I opened do not explain how the three split the work, so I am not going to guess.

What the research says

Moderate Weight loss in obesity without diabetes. The phase 2 trial randomized 338 adults to once-weekly retatrutide or placebo. At 24 weeks weight fell 7.2% (1 mg) to 17.5% (12 mg) versus 1.6% on placebo, and at 48 weeks 8.7% (1 mg) to 24.2% (12 mg) versus 2.1%⁹. In the phase 3 TRIUMPH-1 trial (2,339 adults, 80 weeks), weight fell 17.6%, 23.7%, and 25.0% on 4, 9, and 12 mg versus 3.9% on placebo (P<0.001), counting everyone randomized³. That is the peer-reviewed result, published in the New England Journal of Medicine in November 2026. Eli Lilly funded both trials^9,3.

Moderate Weight and blood sugar in type 2 diabetes. In TRIUMPH-2 (1,152 adults, 80 weeks), weight fell 11.9%, 16.8%, and 18.8% on 4, 9, and 12 mg versus 5.1% on placebo⁷. In a phase 2 diabetes trial of 281 adults, HbA1c fell 2.02 percentage points on retatrutide 12 mg versus 0.01 on placebo and 1.41 on dulaglutide at 24 weeks, and weight fell 16.94% versus 3.00% on placebo at 36 weeks¹⁰. In the 40-week TRANSCEND-T2D-1 trial of 537 adults, HbA1c fell 1.69, 1.86, and 1.94 points on 4, 9, and 12 mg versus 0.81 on placebo, and no severe hypoglycemia was reported⁴.

Moderate Knee osteoarthritis pain. Among the 574 TRIUMPH-1 participants with knee osteoarthritis, the WOMAC pain score fell 3.2, 3.5, and 3.6 points on 4, 9, and 12 mg versus 1.9 on placebo in the trial's main analysis for this outcome, and 3.4, 3.9, and 4.1 versus 2.5 counting everyone randomized. On the 9 mg and 12 mg doses, that is 1.4 to 1.8 points more than placebo³.

Moderate Sleep apnea. In TRIUMPH-1-OSA (243 participants without diabetes), the apnea-hypopnea index fell by 22.9, 34.3, and 31.7 events per hour on 4, 9, and 12 mg versus 9.9 on placebo at 80 weeks. In TRIUMPH-2-OSA (448 participants with diabetes), it fell 19.2, 24.7, and 25.4 versus 10.3⁶. Those are drops from high starting points (58.6 and 55.9 events per hour), and the abstract does not say how many people reached a normal range⁶.

Early Severe obesity with heart disease, from a company press release that is not yet peer-reviewed. Lilly's July 23, 2026 release reports TRIUMPH-3, an 80-week trial of 1,949 adults with a BMI of 35 or more and established cardiovascular disease: weight fell 21.6% on 9 mg and 22.6% on 12 mg versus 3.2% on placebo, by the efficacy estimand explained below. Major heart events were fewer than expected in both groups (44 on retatrutide and 52 on placebo for a five-part composite), and the hazard ratio of 0.82 has a 95% CI of 0.55 to 1.22, which includes no effect¹. These are company figures, and I treat them as preliminary.

Early Liver fat. In a phase 2a trial of 98 adults with metabolic dysfunction-associated steatotic liver disease, drawn from the phase 2 obesity trial, liver fat fell 42.9% (1 mg), 57.0% (4 mg), 81.4% (8 mg), and 82.4% (12 mg) at 24 weeks versus a 0.3% rise on placebo, and 27% to 86% reached normal liver fat (under 5%) versus none on placebo⁵. The abstract reports liver fat, not liver scarring or liver outcomes.

Early Lean mass. In a body composition substudy of the phase 2 diabetes trial (189 enrolled, DXA scans at 36 weeks), total fat mass fell 26.1% on 8 mg and 23.2% on 12 mg versus 4.5% on placebo, and the authors report that the share of weight lost as lean mass was similar to other obesity treatments¹¹. Only 155 people had a baseline scan and 103 finished with both scans, and the abstract gives no lean-mass numbers, so I cannot say how many pounds of muscle or other lean tissue that is¹¹.

Two ways to count weight loss

The journal papers count everyone randomized, including people who stopped the drug (the treatment-regimen estimand)^3,7. Lilly's July 23, 2026 press release leads with the efficacy estimand, which estimates the result had everyone stayed on the drug¹. For TRIUMPH-2 at 12 mg, that is 18.8% in the Lancet paper and 20.8% in Lilly's release^7,1. For TRIUMPH-1 at 12 mg, the journal paper reports 25.0%, while a Pharmacy Times report of Lilly's May 21, 2026 topline announcement gave 28.3% without naming the analysis^3,12. The higher number is a fair answer to "what happens if you stay on it," not the average across everyone who started.

Side effects and stopping

Stomach. In TRIUMPH-2, diarrhea occurred in 27%, 34%, and 34% on 4, 9, and 12 mg versus 13% on placebo, and nausea in 14%, 21%, and 28% versus 8%⁷. In the phase 2 diabetes trial, 35% of retatrutide participants had mild-to-moderate gastrointestinal adverse events versus 13% on placebo¹⁰. In the phase 2 obesity trial, these events were dose-related and mostly mild to moderate, and a lower starting dose partly eased them⁹.
Dysesthesia (an abnormal sensation) occurred in 4%, 6%, and 7% on 4, 9, and 12 mg versus 1% on placebo in TRIUMPH-2⁷, and in 6.4% on both 9 mg and 12 mg versus 1.3% in TRIUMPH-3, per Lilly's release, which says the cases were generally mild to moderate and most resolved during treatment¹.
Low blood pressure. In TRIUMPH-2, hypotension occurred in 1%, 5%, and 6% on 4, 9, and 12 mg versus under 1% on placebo⁷.
Stopping because of side effects. In TRIUMPH-2, permanent discontinuation due to adverse events or death was 4% (4 mg), 12% (9 mg), 8% (12 mg), and 5% (placebo)⁷. In TRIUMPH-3, per Lilly's release, discontinuation due to adverse events was 9.8% and 13.5% versus 4.8%¹. In TRANSCEND-T2D-1 it was 2% to 5% versus 0%⁴. A Pharmacy Times report of Lilly's TRIUMPH-1 topline gives 4.1%, 6.9%, and 11.3% versus 4.9%¹².
Heart rate. In phase 2, dose-dependent heart rate increases peaked at 24 weeks and declined afterward⁹.
Deaths. In TRIUMPH-2, two participants died in the 4 mg group, three in the 9 mg group, one in the 12 mg group, and one on placebo, and the investigators judged all of the deaths unrelated to the study drug⁷. In TRANSCEND-T2D-1, two people died, both on 4 mg, and both deaths were judged unrelated⁴.

Cautions

It is not approved, so there is no FDA label, no approved dose, and no approved use^1,2.
The trials ran 40 to 80 weeks, so they do not show long-term safety^3,4. None of the sources I opened report what happens after stopping.
Most of the evidence comes from Lilly's own program: Lilly funded the trials, its press-release figures are not peer-reviewed, and its release leads with the more favorable analysis^3,7,1.
The FDA has warned about products falsely labeled "for research purposes" and urges consumers not to buy them². A 2026 case report described a woman in her mid-20s with five days of nausea, vomiting, and loose stools after weekly injections of a product reported to contain retatrutide that was never verified; her symptoms resolved within a week¹³.
The body composition data rest on one 36-week substudy with no lean-mass numbers in its abstract¹¹.
I haven't researched how it interacts with a multi-day fast like my monthly one, so this page says nothing about that.

References

Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Eli Lilly and Company press release (PR Newswire); copy read on BioSpace, July 23, 2026.ArticleRead
What it found: Company press release, not peer-reviewed: Lilly calls retatrutide an investigational once-weekly triple hormone receptor agonist and says it plans to submit a Biologics License Application to the FDA in Q1 2027. TRIUMPH-2 (1,152 people with type 2 diabetes and obesity or overweight, 80 weeks) reported weight loss of 12.7% to 20.8% versus 4.0% on placebo and A1C changes of -1.4% to -1.6% from a 7.7% baseline versus -0.2%; diarrhea ran 27.4% to 33.6% versus 13.2% on placebo and dysesthesia 4.5% to 7.3% versus 0.7%.
Limits: A company topline release with the efficacy estimand and no peer review; Lilly's own investor page answered 403 to our checks, so the link goes to the same release as reposted on BioSpace.
U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. Food and Drug Administration (fda.gov), October 1, 2026.Regulatory noticeRead
What it found: FDA page (content current as of October 1, 2026) saying retatrutide and cagrilintide cannot be used in compounding under federal law and have not been found safe and effective for any condition, that FDA has warned companies over unapproved products falsely labeled for research purposes, and that FDA urges consumers not to buy such products, which are of unknown quality.
Limits: The page shows no separate posted or updated date, so the date is the content-current date it states, and it is a regulatory statement, not a study.
Jastreboff AM, Kaplan LM, Davies MJ, Wilding JPH, Ahmad NN, Murray M, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. The New England Journal of Medicine. 2026;395(18):1781-1793.Randomized trialPubMed 42814954 · DOI
What it found: Phase 3 TRIUMPH-1 trial (NCT05929066) randomizing 2,339 adults with obesity and no diabetes to once-weekly retatrutide 4, 9, or 12 mg or placebo for 80 weeks. Weight changed -17.6%, -23.7%, and -25.0% versus -3.9% on placebo (P<0.001), WOMAC knee pain in the 574-person osteoarthritis subgroup fell 3.4, 3.9, and 4.1 points versus 2.5 (ITT estimand), and apnea-hypopnea events per hour in the 243-person sleep apnea subgroup fell 22.8, 34.3, and 32.1 versus 9.6 (ITT estimand).
Limits: Funded by Eli Lilly; the abstract gives no discontinuation or adverse event frequencies beyond saying gastrointestinal events were most common, and its weight results count everyone randomized (treatment-regimen estimand), which gives lower figures than the efficacy estimand Lilly's press releases lead with.
Bajaj HS, Welch M, Shah P, Luna E, Jaouimaa FZ, Liu B, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet (London, England). 2026;407(10546):2402-2413.Randomized trialPubMed 42250575 · DOI
What it found: Forty-week phase 3 trial (NCT06354660) of 537 adults with type 2 diabetes and HbA1c 7.0% to 9.5% randomized 1:1:1:1 to once-weekly retatrutide 4, 9, or 12 mg or placebo. HbA1c fell 1.69%, 1.86%, and 1.94% versus 0.81% on placebo, body weight fell 11.5%, 13.9%, and 15.3% versus 2.6%, discontinuations due to adverse events were 2% to 5% with retatrutide and 0% with placebo, no severe hypoglycemia was reported, and two deaths in the 4 mg group were unrelated to the study drug.
Limits: Funded by Eli Lilly and Company; 40 weeks in people with fairly recent diabetes (mean duration 2.5 years), so it cannot show long-term outcomes.
Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024;30(7):2037-2048.Randomized trialPubMed 38858523 · DOI
What it found: Randomized, double-blind, placebo-controlled phase 2a trial of 98 adults with metabolic dysfunction-associated steatotic liver disease given once-weekly retatrutide 1, 4, 8, or 12 mg or placebo for 48 weeks. At 24 weeks relative liver fat fell 42.9%, 57.0%, 81.4%, and 82.4% versus a 0.3% rise on placebo (all P < 0.001), and normal liver fat (under 5%) was reached by 27%, 52%, 79%, and 86% versus 0% on placebo.
Limits: Ninety-eight people and 24-week liver fat measures, with no biopsy outcomes or liver-disease events, and the study registration (NCT04881760) is the same as the phase 2 obesity trial, with Lilly employees among the authors.
Grunstein RR, Somers VK, Azarbarzin A, Malhotra A, Sands SA, Lucey BP, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. The New England Journal of Medicine. 2026.Randomized trialPubMed 42904878 · DOI
What it found: Two 80-week phase 3 sleep apnea trials, TRIUMPH-1-OSA (243 participants without type 2 diabetes) and TRIUMPH-2-OSA (448 participants with it), with a baseline apnea-hypopnea index of 58.6 and 55.9 events per hour. In TRIUMPH-1-OSA retatrutide 4, 9, and 12 mg cut the index by 22.9, 34.3, and 31.7 events per hour versus 9.9 on placebo, and in TRIUMPH-2-OSA by 19.2, 24.7, and 25.4 versus 10.3 (hybrid-treatment estimand).
Limits: Published ahead of print on October 21, 2026 (volume and pages not yet assigned in the record I opened), and the abstract gives no discontinuation or adverse event percentages.
Bellido V, le Roux CW, Ekinci EI, Bjornstad P, Frias JP, Giblin K, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet (London, England). 2026;408(10563):1455-1472.Randomized trialPubMed 42810372 · DOI
What it found: Phase 3 trial at 92 centers in eight countries of 1,152 adults with obesity and type 2 diabetes randomized 1:1:1:1 to retatrutide 4, 9, or 12 mg or placebo. At week 80 body weight fell 11.9%, 16.8%, and 18.8% versus 5.1% on placebo (treatment-regimen estimand); diarrhea occurred in 27%, 34%, and 34% versus 13%, nausea in 14%, 21%, and 28% versus 8%, and dysesthesia in 4%, 6%, and 7% versus 1%. Permanent discontinuation due to adverse events or death was 4% (4 mg), 12% (9 mg), 8% (12 mg), and 5% (placebo).
Limits: Funded by Eli Lilly and Company; 80 weeks in adults with type 2 diabetes, so it cannot show long-term safety or results in people without diabetes.
Monostra M. Eli Lilly files lawsuits against six companies for allegedly selling retatrutide. Healio, August 14, 2026.ArticleRead
What it found: Healio news report that Lilly sued six companies it says sell counterfeit, unapproved versions of retatrutide, that retatrutide had not yet been reviewed by the FDA, that Lilly plans to submit a biologics license application in the first quarter of 2027, and that an FDA statement of June 15 said retatrutide and cagrilintide are not FDA approved for any condition and cannot be used in compounding under federal law.
Limits: A secondary news report, used only for the FDA-review status and the lawsuits; the FDA's own page is the primary source for the FDA's statements.
Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. The New England Journal of Medicine. 2023;389(6):514-526.Randomized trialPubMed 37366315 · DOI
What it found: Phase 2 double-blind placebo-controlled trial of once-weekly retatrutide for 48 weeks in 338 adults with obesity or overweight. Mean weight change at 24 weeks ran from -7.2% (1 mg) to -17.5% (12 mg) versus -1.6% on placebo, and at 48 weeks from -8.7% (1 mg) to -24.2% (12 mg) versus -2.1%; the most common adverse events were gastrointestinal, dose-related, mostly mild to moderate, and partly eased by a lower starting dose (2 mg versus 4 mg).
Limits: A phase 2 trial funded by Eli Lilly with 338 people for 48 weeks, and the abstract gives no discontinuation figure.
Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet (London, England). 2023;402(10401):529-544.Randomized trialPubMed 37385280 · DOI
What it found: Phase 2 trial of 281 adults with type 2 diabetes at 42 US centers given weekly retatrutide, placebo, or dulaglutide 1.5 mg. At 24 weeks HbA1c fell 0.43% to 2.02% on retatrutide versus 0.01% on placebo and 1.41% on dulaglutide, weight fell 3.19% to 16.94% at 36 weeks, gastrointestinal events were mild to moderate in 35% (67 of 190), and no severe hypoglycemia or deaths were reported.
Limits: A phase 2 dose-finding trial of 24 to 36 weeks, funded by the drug's developer, so it cannot show long-term safety or hard outcomes.
Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. The Lancet. Diabetes & Endocrinology. 2025;13(8):674-684.Randomized trialPubMed 40609566 · DOI
What it found: Body composition substudy of the phase 2 type 2 diabetes trial, with 189 participants enrolled and total fat mass measured by DXA at 36 weeks. Fat mass fell 26.1% on retatrutide 8 mg (pooled) and 23.2% on 12 mg versus 4.5% on placebo and 2.6% on dulaglutide, and the authors report that the proportion of lean mass loss to weight loss was similar to other obesity treatments.
Limits: Only 155 people had a baseline DXA scan and 103 completed treatment, the study ran 36 weeks in people with type 2 diabetes, funded by Eli Lilly, and the abstract gives no lean-mass numbers.
Halpern L. Retatrutide Delivers Bariatric-Level Weight Loss in Pivotal Phase 3 TRIUMPH-1 Trial. Pharmacy Times, May 21, 2026.ArticleRead
What it found: Trade-press report of Eli Lilly's May 21, 2026 topline announcement for TRIUMPH-1: at 80 weeks weight fell 19.0%, 25.9%, and 28.3% on retatrutide 4, 9, and 12 mg, and discontinuation due to adverse events was 4.1%, 6.9%, and 11.3% versus 4.9% on placebo; it says dysesthesia occurred in a subset, was generally mild, and most affected participants continued.
Limits: A news report of company topline results that does not say which estimand the weight figures use and gives no sample size, and the peer-reviewed NEJM paper now supersedes it.
Buzzi RM, Huber LC. Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide. BMJ Case Reports, 2026.ArticlePubMed 42843917 · DOI
What it found: Case report of a woman in her mid-20s with five days of nausea, vomiting, and loose stools that persisted despite intravenous fluids, metoclopramide, ondansetron, and domperidone, after weekly injections of an unverified product reported to contain retatrutide. Symptoms resolved within one week and the Naranjo score of 7 indicated probable causality.
Limits: One person, and the product was never verified to contain retatrutide, so it shows a risk of unverified products and says nothing about the drug as given in trials.