What retatrutide dysesthesia is
Dysesthesia is an unpleasant or abnormal skin sensation. Lilly defines it in the retatrutide trials as "a skin burning sensation and related adverse events".[1] The phase 2 obesity trial described the same signal as skin sensitivity or hyperesthesia, reported in 7% of people on retatrutide against 1% on placebo. None of those cases was severe and none led to stopping treatment.[8]
Not an injection-site reactionDysesthesia is a sensation in the skin, not redness or swelling where the needle went in. The trials counted injection-site reactions separately (see below).
Retatrutide skin sensitivity rates in every trial
Dysesthesia appeared in every phase 3 trial reported so far, at different rates:
| Trial | Population | 4 mg | 9 mg | 12 mg | Comparator |
|---|---|---|---|---|---|
| TRIUMPH-1[4] | Obesity, no diabetes | 5.1% | 12.3% | 12.5% | 0.9% placebo |
| TRIUMPH-1 knee substudy[3] | Obesity + knee osteoarthritis | 6.3% | 16.8% | 15.3% | 0.7% placebo |
| TRIUMPH-4[5][3] | Obesity + knee osteoarthritis | – | 8.8% | 20.9% | 0.7% placebo |
| TRIUMPH-2[6] | Obesity + type 2 diabetes | 4.5% | 5.6% | 7.3% | 0.7% placebo |
| TRANSCEND-T2D-2[7] | Type 2 diabetes | – | 4.8% | 6.5% | 2.7% semaglutide 2 mg |
Patterns in the data
- It rises with dose. In TRIUMPH-1 the rate went from 5.1% on 4 mg to about 12% on 9 and 12 mg.[4]
- It was lower in people with type 2 diabetes. TRIUMPH-2 and TRANSCEND-T2D-2 reported 4.5% to 7.3%, against up to 20.9% in the knee osteoarthritis trials.[6][7][3]
- It is not unique to retatrutide. 2.7% of people on semaglutide reported it in TRANSCEND-T2D-2, and 0.7% to 0.9% on placebo in the other trials.[7][4]
How serious retatrutide skin sensitivity was
In the trial reports, dysesthesia was mostly mild and rarely caused people to stop treatment. The TRIUMPH-4 paper describes the events as "generally mild", and Lilly's medical information says most cases were mild to moderate.[3][1] The share of people who stopped treatment for any side effect is on the retatrutide side effects page.
Skin sensitivity vs injection-site reactions
Injection-site reactions were reported separately, and at lower rates than dysesthesia on the 12 mg dose in TRIUMPH-4:[3]
| Trial | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| TRIUMPH-4 | – | 8.8% | 6.1% | 2.7% |
| TRIUMPH-1 knee substudy | 7.7% | 11.9% | 13.9% | 5.6% |
What is not known yet
- Why retatrutide causes it. The published papers do not establish a mechanism.
- When it starts, how long it lasts and whether it fades on continued treatment. These details are not in the published summaries.
- Whether rates change with the slower escalation schemes being tested in TRIUMPH-9. See the retatrutide clinical trials tracker.
The way retatrutide's doses were stepped up is on the retatrutide dosing page.
Frequently asked questions
What does retatrutide skin sensitivity feel like?
How common is dysesthesia on retatrutide?
Does retatrutide skin sensitivity go away?
Do tirzepatide or semaglutide cause dysesthesia?
In the head-to-head TRANSCEND-T2D-2 trial, 2.7% of people on semaglutide 2 mg reported dysesthesia, against 4.8% and 6.5% on retatrutide 9 and 12 mg.[7]
Sources
- Was dysesthesia reported as an adverse event in the retatrutide TRIUMPH trials?
- Schnitzer TJ et al. Retatrutide in obesity and knee osteoarthritis (TRIUMPH-4)
- Schnitzer TJ et al. Retatrutide in obesity and knee osteoarthritis (TRIUMPH-4, TRIUMPH-1-OA), author accepted manuscript
- Jastreboff AM et al. Retatrutide for obesity (TRIUMPH-1)
- Lilly: retatrutide delivered weight loss of up to 71.2 lbs in TRIUMPH-4
- Bellido V et al. Retatrutide in obesity with type 2 diabetes (TRIUMPH-2)
- Lilly: retatrutide vs semaglutide 2 mg in TRANSCEND-T2D-2
- Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial