Why is my heart racing on retatrutide?
In trials of retatrutide, increases in heart rate were observed. Researchers attribute this to retatrutide activating three receptors at once (GLP-1, GIP, and glucagon), and glucagon can stimulate the heart. In the Phase 2 TRIUMPH trial, the average heart-rate increase peaked around week 24 and then came back down; the Phase 3 TRIUMPH-4 trial showed a small average increase, with overall blood pressure improving. Retatrutide is investigational and not approved; any decision about it, and any symptom you notice, belongs with a licensed provider.
- Phase 2 TRIUMPH (Jastreboff et al., NEJM 2023, NCT04881760): dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter; 338 adults with obesity without type 2 diabetes
- Phase 3 TRIUMPH-4 (68 weeks, n=751 on trial doses): heart rate +a small increase average; systolic BP -8.0 mmHg; diastolic BP -4.3 mmHg
- Overall cardiovascular picture in TRIUMPH-4 was positive despite the heart rate increase
- Mechanism: glucagon receptor activation directly increases heart rate (chronotropy); semaglutide and tirzepatide do not activate glucagon receptors
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