Appetite control

Appetite is kept separate from fat loss because they are not the same request. Some people already have a diet that works and simply want hunger turned down; others are managing grazing or binge patterns where total intake is not really the problem. If what you want is a smaller appetite rather than a smaller waist, this is the more honest list to read.

Six compounds sit at 5/5 and they split across three mechanisms. The incretin agonists — semaglutide, tirzepatide, retatrutide — slow gastric emptying and act on hypothalamic satiety circuits, and they have by far the largest trial base. Cagrilintide is an amylin analogue reaching satiety through a different receptor, which is exactly why it is being trialled in combination with semaglutide rather than against it. Tesofensine is an oral triple monoamine reuptake inhibitor and behaves more like a stimulant than a satiety drug.

The sixth 5/5 entry is MK-677, and it is here because it acts powerfully on appetite, not because it helps: it is a ghrelin receptor agonist and it increases hunger. That is the clearest illustration on this site of why match strength and usefulness are different axes — a strong match tells you a compound engages the system, not which direction it pushes. Beyond that, expect the gastrointestinal side effects to be worst in the week after each dose increase, escalate slowly, and understand that appetite returns when you stop.