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Key monitoring strategies used in these trials include: Regular laboratory assessments (liver enzymes, lipase and amylase, renal function markers, HbA1c and glucose) Renal function monitoring, particularly if significant gastrointestinal adverse effects occur and dehydration is a concern Cardiovascular monitoring, including resting heart rate and blood pressure GLP-1 and glucagon receptor agonism can increase resting heart rate, which requires careful evaluation in those with pre-existing cardiac conditions Calcitonin measurement and thyroid ultrasound where specified by trial protocol, to monitor for any signal related to thyroid C-cell changes (noting that routine thyroid function tests are not the specific safety assessment for this risk) Body composition assessments using imaging tools, which are research-protocol-specific rather than routine clinical monitoring, to evaluate changes in lean muscle mass versus fat mass Patient-reported outcome measures to capture quality-of-life changes and symptom burden over time Ophthalmic assessments in participants with pre-existing diabetic retinopathy, given the potential for early worsening with rapid glycaemic improvement The glucagon receptor component of retatrutide introduces additional monitoring considerations

Supplementary material The Supplementary Material for this article can be found online at: Glossary a GSH and GSSG are used here to refer specifically to the thiol and disulphide forms of glutathione

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