Retatrutide Side Effects: What Trials Actually Reported

The most common side effects of retatrutide in trials were gastrointestinal: nausea, diarrhoea, vomiting and constipation, more often at higher doses. Phase 3 trials also reported dysaesthesia, an altered skin sensation, in up to 20.9% of participants on the highest dose in one trial. Everything below comes from Lilly-funded trials, where participants were supervised and received pharmaceutical-grade drug. For efficacy and the programme overview see our Phase 3 article.

Key points

• In the Phase 2 obesity trial (338 adults, 48 weeks), nausea affected 11% on placebo and 45% on the 12 mg arm; across all retatrutide arms, 8% stopped treatment because of an adverse event, against 0% on placebo [1].
• Dysaesthesia was 7% on retatrutide against 1% on placebo in Phase 2 [1], and rose to 12.5% (TRIUMPH-1) and 20.9% (TRIUMPH-4) at the highest dose in Lilly’s Phase 3 reports [5][6].
• Phase 2 reported 15 serious adverse events in 13 participants (4% in both the retatrutide and placebo groups) and one death, from drowning, judged by the investigator as unrelated [1]. Lilly’s Phase 3 releases do not report serious events or deaths [5][6][7].
• Retatrutide is not approved by any regulator we checked. Products sold online as retatrutide have no safety data and no quality guarantee [12][13][14].

What are the side effects of retatrutide?

The Phase 2 obesity paper (Jastreboff et al., NEJM 2023) randomised 338 adults with obesity to weekly retatrutide or placebo for 48 weeks; 337 took at least one dose. It was funded by Eli Lilly [1]. The authors wrote that the most frequent events were gastrointestinal, mostly mild to moderate, and more frequent at higher doses [1]. “Gastrointestinal adverse events” means nausea, diarrhoea, vomiting, constipation and similar digestive complaints [1].

Beyond that, the paper reported decreased appetite (18% overall), fatigue (7%) and raised lipase, a pancreatic enzyme, in 5% [1]. Increases in heart rate were dose-dependent, peaked at 24 weeks and then declined; the numerical values sit in supplementary tables we did not open [1]. Cardiac arrhythmias, a category that includes supraventricular arrhythmias and conduction disorders, were reported in 6% of retatrutide participants overall (14% in one 8 mg arm) and in 3% on placebo; one severe event of prolonged QT interval occurred in a participant also taking ondansetron [1]. Hypersensitivity events were reported in 9% on retatrutide against 3% on placebo, and injection-site reactions in 2% on retatrutide [1].

How common is nausea?

In the Phase 2 obesity trial, nausea affected 11% of 70 placebo participants, 14% on 1 mg, 18% and 36% in the two 4 mg arms, 17% and 60% in the two 8 mg arms, and 45% on 12 mg (62 participants) [1]. The two arms at each of the 4 mg and 8 mg levels differed in the starting dose, and the paper found events less frequent after the lower start [1]. Vomiting followed the same pattern, from 1% on placebo to 19% on 12 mg [1].

In Lilly’s Phase 3 topline releases (company-reported figures), nausea ran like this:

Trial	Population, duration	Nausea, retatrutide arms	Nausea, placebo
TRIUMPH-1 [6]	2,339 adults with obesity, 80 weeks	28.6% (4 mg), 38.4% (9 mg), 42.4% (12 mg)	14.8%
TRIUMPH-4 [5]	445 adults with knee osteoarthritis, 68 weeks	38.1% (9 mg), 43.2% (12 mg)	10.7%
TRIUMPH-2 [7]	1,152 adults with type 2 diabetes, 80 weeks	13.7%, 20.8%, 28.0% (4, 9, 12 mg)	8.0%
TRIUMPH-3 [7]	1,949 adults with BMI of 35 or more and cardiovascular disease, 80 weeks	21.7% (9 mg), 22.4% (12 mg)	5.8%

The Lancet paper on TRIUMPH-2 gives nausea as 14% (40 of 292), 21% (59 of 284) and 28% (80 participants) against 8% (23 of 289) [9].

What is dysaesthesia?

Dysaesthesia is an abnormal skin sensation. The Phase 2 paper grouped “cutaneous hyperesthesia and skin sensitivity” events: heightened or altered sensation of the skin [1]. They affected 7% of retatrutide participants and 1% on placebo, none were severe or serious, none came with visible skin findings, and none led to stopping treatment [1]. The paper’s special-interest table lists “hyperesthesia or related adverse event” at 13% on 12 mg and 14% in one 8 mg arm [1]. The registry record for the same trial lists allodynia (pain from a touch that is not normally painful) in 4 participants on 12 mg and none elsewhere [2].

Phase 3 rates, as Lilly reported them: TRIUMPH-1 5.1%, 12.3% and 12.5% on 4, 9 and 12 mg against 0.9% on placebo [6]; TRIUMPH-4 8.8% (9 mg) and 20.9% (12 mg) against 0.7% [5]; TRIUMPH-2 4.5%, 5.6%, 7.3% against 0.7%, and TRIUMPH-3 6.4% on both doses against 1.3% [7]. The Lancet TRIUMPH-2 paper reports 4%, 6% and 7% against 1% [9]. Lilly describes the events as generally mild to moderate [5][6]. How long they last, and whether they resolve, is not stated in the releases we read [5][6][7]. The rate rises with dose across Phase 3 reports, but no source we opened explains the mechanism.

Do people stop treatment because of side effects?

In Phase 2, adverse events led to stopping the study drug in 0% on placebo and between 6% and 16% across retatrutide arms, 8% overall; the highest figure was 16% on 12 mg. GI events were the most common reason [1]. Phase 3 reports of discontinuation due to adverse events:

• TRIUMPH-1: 4.1%, 6.9%, 11.3% (4, 9, 12 mg) against 4.9% on placebo [6].
• TRIUMPH-4: 12.2% (9 mg) and 18.2% (12 mg) against 4.0%; among those with BMI of 35 or more, 8.8% and 12.1% against 4.8%. Lilly says rates correlated with baseline BMI and that some people stopped over perceived excessive weight loss [5].
• TRIUMPH-2: 3.8%, 11.6%, 7.7% against 4.9%; TRIUMPH-3: 9.8% and 13.5% against 4.8% [7].
• The Lancet TRIUMPH-2 abstract reports permanent discontinuation due to adverse events or death at 4% (4 mg), 12% (9 mg), 8% (12 mg) and 5% on placebo, a different measure from Lilly’s [9].

Has retatrutide caused serious adverse events in trials?

Serious events have been reported, at rates similar to placebo in Phase 2. In the obesity trial, 15 serious events occurred in 13 participants: 3 of 70 on placebo and 10 of 267 across retatrutide arms [1][2]. The registry lists, among retatrutide participants, a stroke in 2 people (1 mg arm), acute pancreatitis (12 mg), acute cholecystitis (gallbladder inflammation), acute kidney injury, heart failure, a prolonged QT interval, and a death from drowning [2]. One participant in the 12 mg arm had acute pancreatitis, which the paper confirmed as a special-interest event [1]. No medullary thyroid cancer or C-cell hyperplasia was reported [1].

In the Phase 2 diabetes trial (Lancet 2023, Rosenstock et al.; 281 US adults, 36 weeks), the abstract reports no severe hypoglycaemia and no deaths [3]. Gastrointestinal events affected 35% of retatrutide participants (67 of 190), 13% on placebo and 35% on dulaglutide, with 50% (12 of 24) in the 8 mg fast-escalation arm [3]. The registry record lists 11 of 190 retatrutide participants with serious events (3 of 45 on placebo), including acute pancreatitis in 2 and atrial fibrillation in 1 [4]. Funded by Lilly [3].

In Phase 3, the Lancet TRIUMPH-2 abstract (1,152 randomised) reports 7 deaths: 2, 3 and 1 on the 4, 9 and 12 mg doses and 1 on placebo, all judged by investigators to be unrelated to treatment [9]. It also reports hypotension (low blood pressure) in 1%, 5% and 6% against under 1% [9]. The Lilly releases for TRIUMPH-1, -2, -3 and -4 report no serious-event, death or heart-rate figures [5][6][7]. The NEJM abstracts for TRIUMPH-1 and the sleep apnoea trials (691 randomised) say only that gastrointestinal events were most common [8][10]. We did not open any Phase 3 full text.

Regulatory status

• United States, 2026-11-09: not approved. Lilly said on 2026-07-23 it plans to submit a Biologics License Application in the first quarter of 2027 [7]. Our search of the openFDA Drugs@FDA data returned no entry for retatrutide, while the same query found tirzepatide [12].
• United Kingdom: the MHRA said on 2026-07-24 that retatrutide is not authorised there and that anyone selling it is acting illegally [13].
• EU and Germany: not checked; we did not open the EMA or BfArM registers.
• Prescription status: none, because no authorisation exists. The registry lists an expanded-access record, which is a trial-style exception, not an approval [11].
• “Research use only” is a seller’s label. In an FDA warning letter dated 2026-08-24 the agency called such products unapproved new drugs and said the label did not change their intended human use [14].

Risks and unknowns

The trial figures describe supervised adults on pharmaceutical-grade drug, in studies of 36 to 80 weeks, funded by Lilly. They do not describe products sold online as retatrutide. The MHRA says such products have not been tested for safety, quality or effectiveness and may not contain retatrutide [13]. A certificate of analysis tests a sample, not safety; see what a COA proves and what it does not.

Not established in the sources we opened: long-term safety beyond 80 weeks (one extension ran to 104 weeks, with no safety rates given [6]); cardiovascular and kidney outcomes (the TRIUMPH-Outcomes trial, NCT06383390, is active and has no posted results [11]); numerical Phase 3 heart-rate data; use in children, pregnancy or people with serious liver or kidney disease; interactions; Phase 3 serious-event rates from Lilly’s releases; and the duration of dysaesthesia. Phase 2 data come from small arms (23 to 69 participants per arm), so rare events cannot be ruled in or out. Lilly’s own releases are topline and company-reported, and peer-reviewed numbers can differ. On weight loss, one separate open question is body composition; see GLP-1 weight loss and lean mass evidence. Background on a different issue, compounded GLP-1 products, is in our FDA rules explainer.

Frequently asked questions

What are the side effects of retatrutide? In trials, mainly nausea, diarrhoea, vomiting and constipation, plus dysaesthesia, decreased appetite and a dose-related heart-rate rise in Phase 2 [1][5][6]. Most events were reported as mild to moderate.

How common is nausea? It depended on dose and trial. Phase 2 reported 11% on placebo and 45% on 12 mg; Lilly’s TRIUMPH-1 reported 14.8% on placebo and 42.4% on 12 mg [1][6].

What is dysaesthesia? An altered or heightened skin sensation. In TRIUMPH-4, 20.9% on the 12 mg arm and 0.7% on placebo reported it, mostly mild according to Lilly [5].

Is retatrutide safe? Trials found a profile Lilly describes as consistent with other incretin drugs, with serious-event rates similar to placebo in Phase 2 [1][6]. Long-term and outcomes data are missing, and no trial data apply to products sold online [11][13].

Is retatrutide FDA-approved? No, as of 2026-11-09. Lilly plans a US filing in the first quarter of 2027 [7][12].

Research-use-only listings are on the retatrutide compound page.

Sources

1. Jastreboff AM et al., “Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial,” N Engl J Med 389:514-526 (2023), DOI 10.1056/NEJMoa2301972, full text read through a hosted PDF copy; supplementary tables not opened. https://gwern.net/doc/longevity/glp/retatrutide/2023-jastreboff.pdf
2. ClinicalTrials.gov, NCT04881760, results and adverse-event tables (results first posted 2023-09-13); counts summed by us. https://clinicaltrials.gov/api/v2/studies/NCT04881760
3. Rosenstock J et al., retatrutide in type 2 diabetes, Phase 2, Lancet (2023), PMID 37385280, abstract through Europe PMC. https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:37385280&resultType=core&format=json&src=med
4. ClinicalTrials.gov, NCT04867785, results and adverse-event tables (results first posted 2023-07-03); counts summed by us. https://clinicaltrials.gov/api/v2/studies/NCT04867785
5. Eli Lilly and Company, TRIUMPH-4 topline release (2025-12-11), PR Newswire copy. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html
6. Eli Lilly and Company, TRIUMPH-1 topline release (2026-05-21), PR Newswire copy. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html
7. Eli Lilly and Company, TRIUMPH-2 and TRIUMPH-3 topline release (2026-07-23), PR Newswire copy. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html
8. “Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity” (TRIUMPH-1), N Engl J Med (online 2026-09-29), PMID 42814954, abstract through Europe PMC. https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:42814954&resultType=core&format=json&src=med
9. “Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2),” The Lancet (online 2026-09-29), PMID 42810372, abstract through Europe PMC. https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:42810372&resultType=core&format=json&src=med
10. “Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea,” N Engl J Med (online 2026-10-21), PMID 42904878, abstract through Europe PMC. https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:42904878&resultType=core&format=json&src=med
11. ClinicalTrials.gov, query for intervention “retatrutide” (API v2, read 2026-11-09); includes NCT06383390 and expanded-access record NCT07629401. https://clinicaltrials.gov/api/v2/studies?query.intr=retatrutide
12. openFDA, Drugs@FDA API query for active ingredient retatrutide (no match) with tirzepatide as a control (read 2026-11-09). https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:retatrutide&limit=1
13. MHRA, “No summer shortcut for safe weight loss,” GOV.UK (2026-07-24). https://www.gov.uk/government/news/no-summer-shortcut-for-safe-weight-loss
14. U.S. FDA, warning letter to Peak Performance Peptides, ref. 735127 (2026-08-24). https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-performance-peptides-735127-08242026

Not verified and not cited as fact: a patient-guide figure of about 6.7 beats per minute heart-rate rise at 12 mg and a Pharmacy Times summary of Phase 2 discontinuation rates (search snippets only; the paper itself is cited instead); TGA and EMA statements; TRANSCEND results; Phase 3 full texts.

This article is information, not medical advice.