The most common adverse events reported in the Phase 3 retatrutide trials were gastrointestinal — nausea, diarrhea, constipation and vomiting — and they became more frequent as the dose rose. The rates that matter are the ones read against placebo: in TRIUMPH-4, nausea was reported by 43.2% on 12 mg against 10.7% on placebo. The adverse event most specific to retatrutide is dysesthesia, an altered skin sensation, reported by 20.9% on that same arm against 0.7% on placebo.
Retatrutide is investigational. It has no approved label, so no regulator has yet reviewed and published its safety profile. Everything below is taken from Lilly's trial disclosures and, for one trial, a peer-reviewed publication.
What this page is not
This is a report of published trial results, not medical advice, not a safety label, and not a list of what any individual should expect. Participants in these trials were screened, supervised and dose-escalated by clinicians. If you are considering any drug, that is a conversation for a doctor.
The rate on its own means nothing
A page that tells you 43% of people had nausea has told you almost nothing, because it has not told you what happened to the people who got the injection with no drug in it. In TRIUMPH-4 that figure was 10.7%. In TRANSCEND-T2D-1 the placebo nausea rate was 3.7%. The same symptom, in the same programme, at wildly different background rates — because the populations, the durations and the questions asked of participants were different.
So every table below carries its placebo column, and the trials are kept separate rather than pooled into one tidy list. Averaging across them would produce a number that is easier to read and no longer refers to anything.
Tolerability and effect move together
This is the single most important thing on the page, and it is the thing most often left out. The doses that produced the largest weight loss are the doses that produced the most nausea, the most vomiting, the most dysesthesia and the most people stopping.
In TRIUMPH-1, discontinuation because of adverse events ran 4.1% on 4 mg, 6.9% on 9 mg and 11.3% on 12 mg, against 4.9% on placebo. In TRIUMPH-4 it reached 18.2% on 12 mg against 4.0% on placebo. Those headline weight-loss figures of 28% come from the 12 mg arms. A summary that quotes the efficacy of the highest dose alongside a general reassurance about tolerability is quietly describing two different groups.
Adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes.
Adverse event
9 mg
12 mg
Placebo
Diarrhea
30.1%
24.4%
8.7%
Nausea
21.7%
22.4%
5.8%
Constipation
18.0%
15.7%
7.1%
Decreased appetite
13.5%
14.5%
3.0%
Hyperglycemia
3.9%
3.1%
13.4%
Dysesthesia
6.4%
6.4%
1.3%
Urinary tract infection
6.1%
7.0%
5.3%
Stopped treatment because of an adverse event: 9.8% (9 mg) and 13.5% (12 mg), compared with 4.8% on placebo.
Lilly reported these events as generally mild to moderate, with the majority resolving during treatment.
Hyperglycemia is the one row here that runs the other way — 13.4% on placebo against 3.9% and 3.1% on retatrutide. This trial enrolled people with severe obesity, many of them with type 2 diabetes, and the placebo arm was not receiving a drug that lowers blood glucose.
Adults with obesity or overweight and at least one weight-related comorbidity, without diabetes.
Adverse event
4 mg
9 mg
12 mg
Placebo
Nausea
28.6%
38.4%
42.4%
14.8%
Diarrhea
25.2%
34.1%
32.0%
13.5%
Constipation
23.8%
25.9%
26.1%
10.9%
Vomiting
10.6%
22.8%
25.3%
4.8%
Dysesthesia
5.1%
12.3%
12.5%
0.9%
Urinary tract infection
7.5%
8.8%
8.4%
5.3%
Upper respiratory tract infection
14.2%
12.2%
13.1%
11.6%
Stopped treatment because of an adverse event: 4.1% (4 mg), 6.9% (9 mg) and 11.3% (12 mg), compared with 4.9% on placebo.
Lilly reported that the dysesthesia and urinary tract infection events were generally mild to moderate, that the majority resolved during treatment, and that most participants continued taking retatrutide.
Lilly's characterisation: “The types of adverse events seen were generally consistent with trials of other incretin-based therapies.”
Adults with type 2 diabetes inadequately controlled on diet and exercise alone; mean diabetes duration 2.5 years.
Adverse event
4 mg
9 mg
12 mg
Placebo
Nausea
16.4%
19.5%
26.5%
3.7%
Diarrhea
18.7%
26.3%
22.8%
4.5%
Vomiting
15.7%
15.0%
17.6%
2.2%
Dysesthesia
4.5%
2.3%
4.4%
0.0%
Urinary tract infection
0.7%
1.5%
2.9%
0.0%
Stopped treatment because of an adverse event: 2.2% (4 mg), 4.5% (9 mg) and 5.1% (12 mg), compared with 0.0% on placebo.
Lilly stated that these events occurred primarily during dose escalation.
Lilly reported the dysesthesia events as generally mild, with a majority resolving during treatment.
The Lancet publication adds what a press release does not carry: no severe hypoglycaemia occurred in any group, 490 of 537 participants (91%) completed the treatment period on study drug, and two deaths occurred during the trial, both in the 4 mg group and both reported as unrelated to the study drug.
Lilly's characterisation: “Consistent with the types of adverse events seen in clinical trials for other incretin-based therapies.”
NCT05931367 · 68 weeks · Disclosed December 11, 2025
Topline only
Adults with obesity or overweight and knee osteoarthritis, without diabetes.
Adverse event
9 mg
12 mg
Placebo
Nausea
38.1%
43.2%
10.7%
Diarrhea
34.7%
33.1%
13.4%
Constipation
21.8%
25.0%
8.7%
Vomiting
20.4%
20.9%
0.0%
Decreased appetite
19.0%
18.2%
9.4%
Dysesthesia
8.8%
20.9%
0.7%
Stopped treatment because of an adverse event: 12.2% (9 mg) and 18.2% (12 mg), compared with 4.0% on placebo.
Lilly reported the dysesthesia events as generally mild, and said they rarely led to treatment discontinuation.
Lilly stated that overall treatment discontinuation rates were similar across the retatrutide and placebo arms, that the adverse-event discontinuation rates were highly correlated with baseline BMI, and that they included discontinuations for perceived excessive weight loss. In participants whose baseline BMI was 35 or above, the rates were 8.8% (9 mg) and 12.1% (12 mg) against 4.8% on placebo.
Lilly's characterisation: “Consistent with the types of adverse events seen in clinical trials for other incretins.”
Dysesthesia, the one that is not a GLP-1 side effect
Nausea and diarrhea are what anyone familiar with this drug class expects. Dysesthesia is not. It means an altered or uncomfortable sensation in the skin — burning, tingling, prickling, sometimes described as crawling — occurring without an external cause.
The rates vary a great deal across the programme: 20.9% on 12 mg in TRIUMPH-4, 12.5% on 12 mg in TRIUMPH-1, 7.3% in TRIUMPH-2, 6.4% in TRIUMPH-3, and 4.4% in TRANSCEND-T2D-1 — against placebo rates between 0.0% and 1.3%. The spread across trials is wide enough that the honest summary is that this is a real, retatrutide-specific signal whose true frequency is not yet settled.
Lilly has consistently described these events as generally mild and rarely a reason for stopping. Neither the sponsor releases nor the one published paper report how long they lasted after treatment ended. That question is open.
What the topline releases do not contain
Four of the five readouts exist publicly only as press releases. A press release is a summary chosen by the company that makes the drug. It is not a safety table, and the gaps are worth naming precisely.
Serious adverse events. The releases give overall discontinuation rates but do not break out serious adverse events by arm.
Pancreatitis, gallbladder disease, thyroid findings. These are the events regulators scrutinise for this drug class. None of the Phase 3 releases addresses them.
Heart rate. The Phase 2 trial, published in the New England Journal of Medicine in 2023, reported dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards. None of the four Phase 3 topline releases mentions heart rate at all. That is not evidence the finding went away; it is evidence that a press release is not a safety report.
Duration and reversibility. How long events lasted, and what happened after participants stopped, is not disclosed.
Lilly has said detailed results will be presented at medical meetings and published in peer-reviewed journals. When they are, this page will be updated and the change logged on the updates page.
There is no approved safety label — and what that means
For an approved drug, the safety section of the label is the product of the FDA reading the full dataset, including the parts the sponsor would rather summarise. It lists contraindications, warnings, and every adverse reaction above a threshold. Retatrutide has none of this, because no application has been submitted. Lilly has said it plans to file in Q1 2027 — a company projection, not a regulatory date.
This has a direct consequence for anything sold as retatrutide online. In March 2026 the FDA issued a warning letter describing retatrutide products offered for sale as unapproved new drugs, notwithstanding “research use only” labelling. The adverse event rates on this page came from trials using a known compound, at measured doses, under supervision. None of those three conditions applies to a vial of unverified contents, and the rates here should not be read as describing it.
Sources, with the exact release each figure came from.
Questions
What are the most common side effects of retatrutide?
Across the Phase 3 trials the most frequently reported adverse events were gastrointestinal: nausea, diarrhea, constipation and vomiting. Rates depend on the dose and the trial. In TRIUMPH-4, nausea was reported by 43.2% of participants on the 12 mg dose against 10.7% on placebo. Lilly described these events as generally mild to moderate, with the majority resolving during treatment. These are sponsor-reported topline figures for an investigational drug; there is no approved safety label.
What is dysesthesia, and how often did it occur?
Dysesthesia is an altered or uncomfortable skin sensation — burning, tingling or crawling. It is the adverse event that most distinguishes retatrutide from the GLP-1 drugs already on the market. The highest rate reported was in TRIUMPH-4, where 20.9% of participants on 12 mg reported it against 0.7% on placebo. In the other trials the rates were lower, between 2.3% and 12.5% on retatrutide. Lilly described these events as generally mild and said they rarely led to stopping treatment.
Do the side effects get worse at higher doses?
In general yes, and so does the weight loss. Discontinuation because of adverse events rose from 4.1% on 4 mg to 11.3% on 12 mg in TRIUMPH-1, and from 12.2% on 9 mg to 18.2% on 12 mg in TRIUMPH-4, against 4.9% and 4.0% on placebo. The doses that produced the largest weight loss are the same doses that produced the most discontinuation. Any comparison that quotes the best efficacy number and the mildest tolerability number is describing two different groups of people.
Are retatrutide side effects worse than tirzepatide or semaglutide?
No published head-to-head trial answers that. Comparing rates across separate trials with different populations, durations and reporting conventions is not a valid comparison. TRIUMPH-5 is the trial that compares retatrutide with tirzepatide directly and is expected to complete in December 2026.
Does retatrutide have an FDA safety label or a warning list?
No. A label — with contraindications, warnings and a full adverse reactions table — is produced through FDA review, and retatrutide has not been submitted for review. Everything known publicly about its safety comes from trial reports. Anything sold as retatrutide outside a clinical trial has not been evaluated by the FDA, and its contents are unverified.