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Retatrutide appears to produce the fastest weight loss trajectory, with participants in Phase 2 trials losing 24.2% of body weight in just 48 weeks, a pace that outstrips semaglutide and tirzepatide over comparable timeframes

This combination is not typically paired with semaglutide, since tirzepatide already covers GLP-1 receptors and the pairing adds redundancy without new pathway coverage

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