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doi:10.1146/annurev.pharmtox.45.120403.095857

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Broad preclinical activity can be scientifically interesting without automatically translating into safe, predictable, clinically meaningful human outcomes

Glucagon increases energy expenditure and thermogenesis, meaning your body is burning more calories throughout the day at baseline It enhances fat oxidation your body becomes more efficient at using stored fat as fuel GIP works synergistically with GLP-1 to improve insulin sensitivity and nutrient partitioning, meaning the calories you do eat are more likely to go toward muscle and energy rather than fat storage Together, these mechanisms allow for a higher caloric ceiling before fat storage kicks in not unlimited, but meaningfully higher than on GLP-1 alone This is why some people on Reta see better body composition even when eating more than they would on Semaglutide or Tirzepatide

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