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Side effects

Retatrutide side effects

In clinical trials, the most common retatrutide side effects were digestive: nausea, diarrhea, vomiting, constipation and decreased appetite, rising with dose.1812 Abnormal skin sensations (dysesthesia) and low blood pressure were also more frequent than with placebo, and heart rate rose with dose.21 Long-term safety is still being studied.3

This page summarizes published sources for information only. It is not medical advice and does not tell anyone to use a product. Questions about your own health belong with a licensed clinician. For questions about an order or a product, contact us.

Most common: digestive side effects

Gastrointestinal events were the most common adverse events in the phase 1b, phase 2 and phase 3 trials.415 In the phase 2 obesity trial they were dose-related, mostly mild to moderate, and partly reduced by a lower starting dose.1 In the 40-week TRANSCEND-T2D-1 trial they subsided over time.6

Side effect Retatrutide Placebo Trial
Nausea 14% (4 mg), 21% (9 mg), 28% (12 mg) 8% TRIUMPH-22
Nausea 45% (28 of 62) on 12 mg 11% (8 of 70) Phase 2 obesity7
Nausea 21.7% (9 mg), 22.4% (12 mg) 5.8% TRIUMPH-3 topline9
Nausea 38.1% (9 mg), 43.2% (12 mg) 10.7% TRIUMPH-4 topline8
Diarrhea 27% (4 mg), 34% (9 mg), 34% (12 mg) 13% TRIUMPH-22
Diarrhea 30.1% (9 mg), 24.4% (12 mg) 8.7% TRIUMPH-3 topline9
Diarrhea 34.7% (9 mg), 33.1% (12 mg) 13.4% TRIUMPH-4 topline8
Vomiting 19% (12 of 62) on 12 mg 1% (1 of 70) Phase 2 obesity7
Vomiting 20.4% (9 mg), 20.9% (12 mg) 0.0% TRIUMPH-4 topline8
Constipation 16% (10 of 62) on 12 mg 3% (2 of 70) Phase 2 obesity7
Constipation 18.0% (9 mg), 15.7% (12 mg) 7.1% TRIUMPH-3 topline9
Constipation 21.8% (9 mg), 25.0% (12 mg) 8.7% TRIUMPH-4 topline8
Decreased appetite 29% (18 of 62) on 12 mg 9% (6 of 70) Phase 2 obesity7
Decreased appetite 13.5% (9 mg), 14.5% (12 mg) 3.0% TRIUMPH-3 topline9
Decreased appetite 19.0% (9 mg), 18.2% (12 mg) 9.4% TRIUMPH-4 topline8

TRIUMPH-2 is a published phase 3 trial of 1,152 adults with type 2 diabetes over 80 weeks.2 "Phase 2 obesity" is the registry's posted results for the 48-week trial of 338 adults.71 TRIUMPH-3 (1,949 adults, 80 weeks) and TRIUMPH-4 (445 adults, 68 weeks) figures are company-reported toplines.98

Other effects seen more often than with placebo

  • Abnormal skin sensations (dysesthesia): 4%, 6% and 7% on 4, 9 and 12 mg in TRIUMPH-2, versus 1% on placebo.2 Company toplines reported 6.4% in both TRIUMPH-3 dose groups versus 1.3%, and 8.8% and 20.9% in TRIUMPH-4 versus 0.7%.98 Lilly called them generally mild to moderate in TRIUMPH-3, and generally mild and rarely a reason to stop in TRIUMPH-4.98 A 2026 pharmacovigilance review describes dysesthesia, particularly burning skin sensations, with GLP-1 receptor drugs and notes it in retatrutide trials.10
  • Low blood pressure (hypotension): 1%, 5% and 6% on 4, 9 and 12 mg in TRIUMPH-2, versus under 1% on placebo.2
  • Faster heart rate: in the 48-week phase 2 obesity trial, heart rate rose with dose, peaked at 24 weeks and then declined.1
  • Urinary tract infections: the TRIUMPH-3 topline reported 6.1% and 7.0%, versus 5.3% on placebo, and called them generally mild to moderate.9 In the phase 2 diabetes trial, 5 of 46 people on 12 mg had one, versus 2 of 45 on placebo.11

Stopping because of side effects

More people stopped retatrutide than placebo because of adverse events:

  • TRIUMPH-2: 4%, 12% and 8% on 4, 9 and 12 mg, versus 5% on placebo (adverse events or death).2
  • TRIUMPH-3 topline: 9.8% and 13.5% on 9 and 12 mg, versus 4.8%.9
  • TRIUMPH-4 topline: 12.2% and 18.2%, versus 4.0%.8 Lilly said these rates were highly correlated with starting BMI and included stops for perceived excessive weight loss.8 In people with a starting BMI of 35 or higher, they were 8.8% and 12.1%, versus 4.8%.8
  • TRANSCEND-T2D-1: 2% to 5%, versus 0% on placebo.6

Rare and serious events

The two phase 2 trials (338 adults with obesity and 281 with type 2 diabetes) recorded isolated serious events:711

  • Acute pancreatitis: 1 of 62 people on 12 mg in the obesity trial, and 2 cases in the diabetes trial (0.5 mg and 8 mg groups).711
  • Gallbladder inflammation (cholecystitis): 1 acute case in 35 people on 8 mg in the obesity trial, and 1 chronic case in 24 people on 8 mg in the diabetes trial.711
  • Diabetic ketoacidosis: 1 of 46 people on 12 mg in the diabetes trial.11
  • QT prolongation on the heart tracing: 1 of 62 people on 12 mg.7

Single cases like these cannot show whether the drug caused them. No severe low blood sugar (hypoglycemia) was reported in the phase 2 diabetes trial (281 adults) or the phase 3 TRANSCEND-T2D-1 trial (537 adults).126

Reports from outside trials

  • Persistent vomiting: a woman in her mid-20s came to hospital after 5 days of persistent nausea and repeated vomiting.13 She had received 4 weekly, stepped-up injections of an unverified product reported to contain retatrutide, given in a wellness setting by a self-described life coach, and the authors rated the link as probable.13
  • Ketosis in type 1 diabetes: a man in his mid-30s with type 1 diabetes injected an online product marketed as retatrutide.14 He developed severe vomiting, diarrhea and ketosis (4.3 mmol/L), then repeated low blood sugar during recovery.14 His stool culture also grew Shigella, so the authors could not separate the effects of the infection and the product.14
  • Liver injury in Australia: health officials in Victoria linked six cases of acute liver toxicity to unapproved products labeled retatrutide, possibly from a contaminant.15
  • Social media reports: a 2026 study analyzed 148,640 retatrutide-related Reddit posts and comments from 38,936 users.16 Among 7,823 users reporting current use and at least one symptom, with weight-loss and appetite-suppression terms excluded, the most common were increased appetite (17.1%), fatigue (15.2%), increased energy (12.4%) and nausea (11.6%), then food craving (7.3%), insomnia (6.1%) and faster heart rate (4.8%).16 The authors call the findings hypothesis-generating: the reports may reflect other peptides used at the same time or misattribution, and these users may not represent all users.16

Warnings

  • Unapproved products: FDA urges consumers not to purchase unapproved retatrutide falsely labeled for research, which it says is of unknown quality and may be harmful.17
  • Injection risk: FDA notes that injectable products bypass some of the body's defenses against toxins and microorganisms, so they can cause serious harm.18
  • Signs of liver injury: Victoria's health department strongly advises people not to use unapproved peptide products, including products labeled retatrutide.15 It tells anyone who develops tiredness, abdominal pain, itchy skin, dark urine, yellow eyes or skin, or easy bruising after using them to seek medical attention promptly.15
  • Type 1 diabetes: retatrutide has no established role in it, and a case report describes dangerous ketosis and later repeated low blood sugar.14
  • Unknown long-term effects: the TRIUMPH-3 cardiovascular comparison was not conclusive, and the heart and kidney outcomes trial runs to about February 2029.93
  • Adults only in trials: published phase 3 trials enrolled adults aged 18 or older.26

More on Retatrutide

  • Retatrutide dosage

    Published dosing information for Retatrutide from clinical trials, with its source, and why it is not advice for you.

Frequently asked questions

What are the potential side effects of taking retatrutide?

In trials, the most common were digestive: nausea, diarrhea, vomiting, constipation and decreased appetite.812 In the 80-week TRIUMPH-2 trial, nausea affected 28% of people on 12 mg versus 8% on placebo, and diarrhea 34% versus 13%.2 Dysesthesia and low blood pressure were also more common than with placebo.2

How long does it take to have side effects from retatrutide?

Trial reports do not give an exact time to onset.16 In the phase 2 obesity trial, digestive side effects were dose-related and fewer when treatment started at 2 mg rather than 4 mg.1 In the 40-week TRANSCEND-T2D-1 trial, they were mostly mild to moderate and subsided over time.6 Heart rate increases peaked at 24 weeks and then declined.1

What are the potential drug interactions with retatrutide peptide?

Lilly ran interaction studies with midazolam, warfarin and caffeine (completed 2023) and with metoprolol (completed 2025), but as of October 2026 no results are posted.1920 A 2023 paper by Lilly scientists is titled as showing that retatrutide delays gastric emptying; its methods could not be checked.21 The label of the approved GLP-1 drug Wegovy warns that slower stomach emptying may affect absorption of oral medicines.22

Is retatrutide safe?

Its safety is still being studied.3 Trials of up to 80 weeks found mostly digestive side effects, plus more dysesthesia and low blood pressure than placebo.2 A 10,000-person heart and kidney outcomes trial is not due to finish until about 2029.3 FDA says retatrutide has not been found safe and effective for any condition.17 Products sold outside trials add risks of wrong content and contamination.2315

Does retatrutide cause muscle loss?

Some of the weight lost is lean mass.24 In a phase 2 substudy of adults with type 2 diabetes, total fat mass fell 23.2% on 12 mg at 36 weeks, versus 4.5% on placebo.24 The share of weight lost as lean mass was similar to other obesity treatments.24 The study did not show muscle gain.24

Written by D2C Peptides Editorial Team.

Pending qualified review.

Updated .

Sources

  1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine (PubMed record, National Library of Medicine), 2023.
  2. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. The Lancet (PubMed record, National Library of Medicine), 2026.
  3. ClinicalTrials.gov NCT06383390 (TRIUMPH-Outcomes). ClinicalTrials.gov, National Library of Medicine, 2026.
  4. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet (PubMed record, National Library of Medicine), 2022.
  5. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). New England Journal of Medicine (PubMed record, National Library of Medicine), 2026.
  6. 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. The Lancet (PubMed record, National Library of Medicine), 2026.
  7. ClinicalTrials.gov NCT04881760: A Study of LY3437943 in Participants Who Have Obesity or Are Overweight (posted results: adverse events). ClinicalTrials.gov, National Library of Medicine, 2023.
  8. Lilly's 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 (press release, December 11, 2025; PR Newswire copy on Finviz). Eli Lilly and Company via PR Newswire, 2025.
  9. What are the results of retatrutide from TRIUMPH-3 in adults with severe obesity and established cardiovascular disease? (Lilly Medical answer, last reviewed July 23, 2026). Eli Lilly and Company (Lilly Medical), 2026.
  10. Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review. European Journal of Clinical Pharmacology (PubMed record, National Library of Medicine), 2026.
  11. ClinicalTrials.gov NCT04867785: A Study of LY3437943 in Participants With Type 2 Diabetes (posted results: adverse events). ClinicalTrials.gov, National Library of Medicine, 2023.
  12. 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. The Lancet (PubMed record, National Library of Medicine), 2023.
  13. Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide. BMJ Case Reports (PubMed record, National Library of Medicine), 2026.
  14. Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis. Cureus (PubMed record, National Library of Medicine), 2026.
  15. Toxicity linked to unapproved peptide product labelled Retatrutide (health alert, issued 19 June 2026). Department of Health, Victoria (Australia), 2026.
  16. Self-Reported Adverse Effects Among Social Media Users Taking Nonapproved Retatrutide. JAMA Network Open (PubMed Central full text), 2026.
  17. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. Food and Drug Administration, 2026.
  18. Warning Letter to Gram Peptides (MARCS-CMS 721806), March 31, 2026. U.S. Food and Drug Administration, 2026.
  19. ClinicalTrials.gov NCT05445232: A Drug-Drug Interaction (DDI) Study of LY3437943 in Obese Participants. ClinicalTrials.gov, National Library of Medicine, 2023.
  20. ClinicalTrials.gov NCT06808802: Effect of retatrutide on metoprolol pharmacokinetics. ClinicalTrials.gov, National Library of Medicine, 2025.
  21. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes, Obesity and Metabolism (PubMed record, National Library of Medicine), 2023.
  22. WEGOVY (semaglutide) injection, prescribing information (2021 approval label). U.S. Food and Drug Administration (Drugs@FDA), 2021.
  23. Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia. Drug and Alcohol Review (PubMed Central full text), 2026.
  24. 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 (PubMed record, National Library of Medicine), 2025.