Rankings / Weight Loss — Incretins & Amylin
Retatrutide
Weight loss · GLP-1/GIP/glucagon agonist (triple)
Tier B+
What this is
Jastreboff 2023: ~24% weight loss at 48 weeks in Phase 2 — trajectory suggested continued loss past 48 weeks. TRIUMPH program (Eli Lilly) is a 4-trial basket: TRIUMPH-1 (n=2300, obesity, primary completion April 2026), TRIUMPH-2, TRIUMPH-3 (obesity + CVD), TRIUMPH-4 (OA standalone). Plus TRANSCEND-CKD Ph2b kidney mechanism (n=146, baseline characteristics published Oct 2025), TRIUMPH-Outcomes cardio-renal CVOT (NCT06383390), and head-to-head retatrutide vs tirzepatide (NCT06662383, n=800, completion Dec 2026). Potentially the most effective weight loss agent yet tested. Not yet FDA approved.
Mechanism
Triple agonist: GLP-1 + GIP + glucagon receptors; glucagon arm adds energy expenditure in addition to appetite suppression
Dose & route
Phase 2 used up to 12 mg SC weekly; Phase 3 weekly SC
Citations
- https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- https://doi.org/10.1111/dom.70209
- https://doi.org/10.1093/ndt/gfaf230
- https://clinicaltrials.gov/study/NCT05929066
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This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.