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Briefly, wild-type (wt, 5′-GAGTGTGGATGACCCTTGGT-3′) or mutant (mut, 5′-CTCACACCTACTGGGAACCA-3′) sequence in MBOAT1 promoter region or wt (5′-GGTAAAGAGGCGCGGGGA-3′) or mut (5′-CCATTTCTCCGCGCCCCT-3′) sequence in METTL1 promoter region was fused into luciferase pGL3-basic reporter vector (Promega, Madison, USA) to construct pmirGLO-MBOAT1-wt/-mut or pmirGLO- METTL1 -wt/-mut (sequences in Supplementary Table S6)
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The 8mg dose achieved 21.1% weight loss (matching Zepbound’s efficacy) with lower side effects: 24% nausea versus 28% at 12mg, 8.4% discontinuation versus 11.2%
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