8%. 15%. 22.5%. 29%.
Four medications. One decade. Each generation adds one more pathway than the last.
But that's just weight. In December 2025, Eli Lilly presented the Phase 3 TRIUMPH-4 results: retatrutide activated all three signals at once, and the effects reached well beyond the scale. (The figures below come from the trial population: adults with obesity and varied metabolic baselines. Individual effects scale with where each person started.)
Body composition
- 29% average weight loss.
- 76% improvement in joint pain.
- One in eight reported complete pain relief.
Cardiovascular
- A 14-point drop in systolic blood pressure.
- A 27% drop in non-HDL, the cholesterol that matters for risk.
- A 41% reduction in triglycerides.
Metabolic
- 86% average liver fat reduction.
- 93% saw liver fat return to normal.
- A 71% drop in fasting insulin.
Each generation adds one more pathway. GLP-1 quiets appetite by reaching the hypothalamus, the brainstem, and the reward areas. GIP (another gut hormone) improves how insulin and fat tissue work together. Glucagon tells the liver to release stored energy. Three signals. Three different mechanisms. The newer drugs reach further than hunger: into blood pressure, cholesterol, joint pain, and the liver itself.
What this means in practice: what changed over a decade is not just how much weight comes off. It is how many metabolic pathways a single medication can touch at once. Retatrutide is not a stronger Ozempic. It is a different drug that activates three levers at once instead of one. The effects on blood pressure, cholesterol, and the liver are not side benefits. They are direct consequences of the added pathways. Open questions remain: why does the same dose produce different results in different people? Some lose 8 percent, others 22 percent, on identical doses. Those questions drive the next decade of research.
