Why does increasing Reta help with weight loss if CICO is what matters?

r/Retatrutide post author (u/amvu) posed a confusion: since weight loss is essentially a calorie deficit (CICO), why does increasing the retatrutide dose (from 2mg to higher) continue to reduce weight? Several commenters (u/Rigorous_Mastication, u/DonBrother9000, u/soilentgibby) offered mechanistic explanations: retatrutide is Eli Lilly's GLP-1/GIP/glucagon triple receptor agonist; the glucagon receptor is significantly activated above 4mg and can raise basal metabolic rate (BMR), so it does not rely solely on appetite suppression; those with insufficient appetite suppression at low doses only see results after increasing the dose. Meanwhile, u/working-mama- and others warned that very low calorie intake carries risks of hair loss, muscle loss, and gallstones, and u/ModernLifelsWar pointed out that excessive dieting slows metabolism and actually reduces calorie expenditure. The consensus: CICO remains the dominant factor, but the human body is not simple arithmetic. Factually, retatrutide is indeed an investigational triple agonist not yet approved (BLA planned for Q1 2027). Speculatively, individual experiences regarding 'dose—metabolism—plateau' are largely anecdotal.

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