---
title: "Dysesthesia"
definition: "An abnormal sensation that may include tingling, numbness, burning, or altered touch perception, typically in the extremities. A safety signal reported in retatrutide's Phase 3 trials, not seen with semaglutide or tirzepatide."
url: https://retatrutide.med/glossary/dysesthesia
category: "condition"
source: retatrutide.med
sourceType: "glossary term"
license: CC-BY-NC-SA-4.0
canonical: https://retatrutide.med/glossary/dysesthesia
---
## Dysesthesia

Dysesthesia refers to an unpleasant abnormal sensation that occurs either spontaneously or in response to a normally non-painful stimulus. Reported sensations include tingling, numbness, burning, prickling, or altered touch perception, typically affecting the hands, feet, or other peripheral areas of the body. Dysesthesia is distinct from paresthesia (which is the broader category of altered sensation including non-unpleasant tingling) and from neuropathic pain.

In retatrutide clinical development, dysesthesia was reported as a new safety signal in Phase 3 trials at rates that exceeded placebo. The mechanism is not fully established but is most likely related to the glucagon receptor component of retatrutide's triple-agonist mechanism — semaglutide (GLP-1 alone) and tirzepatide (GIP/GLP-1) have not reported a comparable signal, and survodutide (GLP-1/glucagon dual agonist) is being monitored for the same finding.

Reported dysesthesia incidence at the 12 mg dose:

- **TRIUMPH-4** (obesity + knee osteoarthritis, 68 weeks): 20.9% versus 0.7% on placebo
- **TRIUMPH-1** (obesity, no T2D, 80 weeks): 12.5% versus 0.9% on placebo

In both trials, dysesthesia events were predominantly mild to moderate in severity, typically emerged during the dose escalation phase, and most participants continued treatment. The lower TRIUMPH-1 rate compared to TRIUMPH-4 may reflect differences in baseline comorbidity and population age. Full characterization of the signal is expected with the peer-reviewed publication and additional TRIUMPH program readouts.