Orforglipron vs Retatrutide
Two investigational molecules pulling in opposite directions: an oral small molecule chasing access, and an injectable triple agonist chasing maximum effect.
Orforglipron
~11% in ATTAIN-1; a scalable oral pill whose appeal is access, not peak efficacy. Investigational.
Full Orforglipron evidence reviewRetatrutide
~24% in its Phase 2 trial — the largest figure reported for any incretin, but still investigational.
Full Retatrutide evidence reviewSide by side
| Orforglipron | Retatrutide | |
|---|---|---|
| Marketed for | Weight loss, type-2 diabetes | Weight loss |
| Evidence grade | Clinical data | Clinical data |
| Family | GLP-1 / incretin | GLP-1 / incretin |
| Regulatory status | Investigational | Investigational |
| How it's obtained | Research-only | Research-only |
| Key human source | ATTAIN-1, NEJM 2025 | Phase 2, NEJM 2023 |
marks a row where the two differ. Evidence grades come from our evidence matrix, which grades each molecule on the human data for the use it is marketed for.
Our verdict
Neither is approved, and neither is legitimately available outside a clinical study. Retatrutide reported about 24.2% mean weight loss at 12 mg in its 48-week Phase 2 obesity trial, the largest figure reported for any incretin, with a curve that had not clearly plateaued. Orforglipron reported about 11% in ATTAIN-1, but it is a once-daily non-peptide tablet with no food or water restrictions, which is the entire point of the molecule. They have not been compared directly, and neither has long-term cardiovascular or renal outcomes data.
Orforglipron fits if
You think the binding constraint on GLP-1 therapy is manufacturing, cost, and adherence rather than peak efficacy.
Retatrutide fits if
You are following the upper limit of what incretin pharmacology can do and accept that the evidence is still Phase 2.