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Individuals with the following conditions may be at heightened risk and should be assessed carefully: Pre-existing arrhythmias , including atrial fibrillation or supraventricular tachycardia, given the drug's association with elevated resting heart rate Heart failure , particularly where heart rate control is a key management goal Ischaemic heart disease , where any increase in myocardial oxygen demand could be clinically significant Uncontrolled hypertension , although retatrutide may itself reduce blood pressure over time Patients on rate-modifying medications such as beta-blockers or calcium channel blockers whilst no direct pharmacokinetic drugdrug interactions have been established, the heart rate effects of retatrutide may complicate clinical management and require closer monitoring Patients with a recent acute coronary syndrome, decompensated heart failure, or unstable angina are typically excluded from clinical trials of this class of agent

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Appetite reduction is often the earliest noticeable effect, reported within the first one to two weeks due to GLP-1 activity on hypothalamic satiety signalling