Why is my heart racing on retatrutide?
Heart rate increases are expected on retatrutide. This is because retatrutide activates three receptors at once - GLP-1, GIP, and glucagon - and glucagon directly stimulates the heart. In the Phase 2 TRIUMPH trial, heart rate increases peaked around week 24 and then came back down. Phase 3 TRIUMPH-4 averaged a 5 to 7 bpm increase at the 12 mg dose, with overall blood pressure actually improving. Call a doctor if your resting heart rate stays above 100 bpm or if you have palpitations with chest pain or dizziness.
- 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 12 mg): heart rate +5 to 7 bpm 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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