The weight-loss peptides have moved faster than almost any drug class in recent memory. Two names dominate the conversation, and the trial data behind them is worth reading properly.
Tirzepatide
Tirzepatide is a dual agonist, hitting both the GLP-1 and GIP receptors. In SURMOUNT-1, participants without diabetes on the highest dose lost around a fifth of their body weight over 72 weeks. That was a step change from what single-agonist drugs had achieved.
Retatrutide
Retatrutide adds a third target, the glucagon receptor. Glucagon agonism raises energy expenditure rather than only suppressing appetite, which is the mechanistic argument for why it might go further. In the phase 2 trial, mean weight reduction at the top dose reached roughly a quarter of body weight at 48 weeks.
Reading the numbers honestly
Two cautions. First, these are trial averages with structured support behind them, not typical outcomes for someone self-administering. Second, retatrutide is still investigational, and phase 2 results have a long history of softening in phase 3.
Side effects
Gastrointestinal effects dominate both. Nausea, vomiting and constipation cluster in the titration period and are the main reason people discontinue. Slow escalation is the single most useful lever for tolerating either compound.