Retatrutide
Retatrutide is a first-in-class "triple-G" agonist that activates the GLP-1, GIP, and glucagon receptors simultaneously. The glucagon arm is the novel one — it appears to raise energy expenditure and drive fat out of the liver, on top of the appetite suppression seen with existing GLP-1 drugs. In Eli Lilly's Phase 3 TRIUMPH program, retatrutide produced average weight reductions in the ~28–30% range — the highest reported for any obesity medication to date. It remains investigational and is not FDA-approved. Retatrutide is for research use only.
Evidence Summary
Phase 2 (NEJM, 2023): 24.2% mean body-weight reduction at 48 weeks (12 mg). Phase 2a MASLD trial (Nature Medicine, 2024): ~82% relative reduction in liver fat, with 86% of participants reaching normal liver fat (<5%) at 24 weeks. Phase 3 TRIUMPH-1 (2025, n=2,339): 28.3% average weight loss at 80 weeks (12 mg) — up to 30.3% in a subgroup extended to 104 weeks — with 45.3% of participants losing ≥30% of body weight, a threshold historically linked to bariatric surgery. Phase 3 TRIUMPH-4 (Dec 2025, n=445 with knee osteoarthritis): 28.7% weight loss (efficacy estimand), a 14 mmHg drop in systolic blood pressure, meaningful knee-osteoarthritis pain relief, and improvements in triglycerides, non-HDL cholesterol, and hs-CRP. Cardiovascular and diabetes outcome trials (TRIUMPH-2 and -3) are still reading out. Figures are attributable to the specific trial cited and vary by dose and analysis method.
Evidence Scale
Mechanism of Action
Triple agonism: GLP-1 receptor activation reduces appetite and improves insulin secretion. GIP receptor activation enhances fat metabolism and energy expenditure. Glucagon receptor activation increases hepatic energy expenditure, thermogenesis, and fat oxidation. The three pathways synergize for maximal metabolic impact beyond dual agonists.
Who Is This For?
Not yet approved. Studied indications: obesity/overweight with a weight-related comorbidity, type 2 diabetes, MASLD/MASH, and obesity-related knee osteoarthritis. Likely to target severe obesity or patients who have plateaued on single- or dual-agonist GLP-1 therapy. Any use must await regulatory approval and occur under qualified medical supervision.
Protocol & Dosing
Dose
Research use only. Trial dosing escalated weekly to 1 mg, 4 mg, 8 mg or 12 mg subcutaneously. Product available in 10, 15, 20 and 30 mg. Microdosing is also being done at 0.5 mg to 1 mg per week.
Frequency
Weekly injection
Duration
Study durations: 24 weeks (MASLD Phase 2a), 48 weeks (Phase 2 obesity), 68 weeks (TRIUMPH-4), 80 weeks (TRIUMPH-1), with a 104-week subgroup.
Protocol Summary
Investigational triple-agonist studied in Eli Lilly's Phase 3 TRIUMPH program. Trials escalated weekly subcutaneous dosing to 4, 8/9, or 12 mg. TRIUMPH-1 (n=2,339) and TRIUMPH-4 (n=445) reported dose-dependent weight loss up to ~28–30% at 68–80 weeks. Regulatory filing/approval anticipated 2026–2027 pending completion of the full TRIUMPH program.
Interactions & Precautions
Contraindications
- Investigational — full contraindication profile not yet established
- Personal/family history of medullary thyroid carcinoma or MEN 2 (class-wide GLP-1 caution)
- Caution with hepatic dysfunction given glucagon-receptor activation
- Pregnancy and breastfeeding
Potential Risks
- •Discontinuation due to adverse events rose with dose (~11% at 12 mg vs ~5% placebo, TRIUMPH-1)
- •Long-term cardiovascular safety still under study (outcome trials ongoing)
- •Lean-mass preservation not fully characterized
- •Potential hypoglycemia risk when combined with other glucose-lowering therapy
Potential Side Effects
Practitioner Notes
Clinical annotations from Dr. Goel
Dr. Sanjeev Goel: Retatrutide is one of the most exciting metabolic compounds in a decade — the glucagon axis may be what finally couples fat loss with genuine metabolic repair rather than just appetite reduction. But "most exciting" is not "risk-free." Dosing, titration, and monitoring matter enormously here — heart rate, lean mass, and GI tolerance in particular — which is exactly why this belongs in a supervised protocol, not a guess-and-check experiment.
Dr. Sanjeev Goel
Chief Medical Officer, Peak Human
Purchase Retatrutide
Retatrutide (RET) — available as a pre-filled pen, cartridge refill, or vial in 10, 15, 20, and 30 mg through BioXSciences, an independent third-party supplier. Peak Human does not sell or ship these products. Research use only.
For research use only. Investigational compound; a summary of published research, not a treatment claim. Use under medical supervision.
Related GLP-1 interventions
Cost & Access
Cost Range
TBD
Accessibility
Availability varies by location
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