LGD-4033 (Ligandrol) for Lean Mass Building — SARMs
Most clinically studied SARM with Phase II data for hip fracture recovery. Viking Therapeutics VK5211. NOT FDA-approved.
Overview
LGD-4033 (Ligandrol), also known as VK5211 under Viking Therapeutics development, is a non-steroidal selective androgen receptor modulator originally developed by Ligand Pharmaceuticals. It is the most extensively studied SARM in human clinical trials, with completed Phase I (Basaria et al., 2013; PMID: 22459616) and Phase II studies. The Phase I randomized controlled trial in 76 healthy men demonstrated dose-dependent increases in lean body mass (up to 1.21 kg at 1.0mg/day over 21 days) with concurrent fat mass reduction, without significant changes in PSA, hematocrit, or liver enzymes at tested doses. Viking Therapeutics completed a Phase II trial (NCT02578095) in patients recovering from hip fracture, demonstrating statistically significant dose-dependent lean mass gains at 12 weeks versus placebo. LGD-4033 has an oral half-life of 24-36 hours, supporting once-daily dosing. The compound shows strong binding affinity for the AR (Ki ~1nM) with approximately 500-fold selectivity for muscle and bone over prostate. However, dose-dependent suppression of total testosterone, SHBG, and HDL cholesterol was observed in clinical trials. At 1.0mg/day, total testosterone decreased by approximately 50% from baseline but recovered within 35 days of cessation without PCT. LGD-4033 has been the subject of multiple WADA anti-doping violations and is prohibited in sport. Several cases of liver injury have been reported with gray-market products (PMID: 32523785). It is NOT FDA-approved for any indication and remains investigational.
Indications
- Phase II investigation for lean mass recovery after hip fracture surgery (VK5211)
- Research into muscle wasting prevention in cancer cachexia
- Potential treatment for age-related sarcopenia and frailty
- Investigation of bone mineral density improvement in osteoporosis
- Research into functional recovery acceleration post-surgery
- Preclinical investigation for stress urinary incontinence
Mechanism of Action
LGD-4033 administered orally with high bioavailability. Rapidly absorbed with Tmax ~1-2 hours. Half-life of 24-36 hours allows once-daily dosing with steady-state achieved within 7 days
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| LGD-4033 (Ligandrol) | 5 mg/day | Once daily | Common research dose; significant lean mass gains with moderate suppression |
| LGD-4033 (Ligandrol) | 10 mg/day | Once daily | Higher dose; greater efficacy but more pronounced suppression |
| LGD-4033 (Ligandrol) | 1.0 mg/day | Once daily | Phase I clinical trial dose; demonstrated 1.21kg lean mass gain in 21 days |
Evidence Grade
GRADE D
Safety & Contraindications
- NOT FDA-approved for any human indication — investigational compound only
- Dose-dependent testosterone suppression — 50% reduction at 1.0mg/day in Phase I trial
- SHBG suppression observed — free androgen index may not reflect total T changes
- HDL cholesterol reduction in dose-dependent manner in clinical trials
- Drug-induced liver injury reported with gray-market products (PMID: 32523785)
- Testosterone recovery takes approximately 35 days post-cessation at clinical doses
- WADA prohibited substance — multiple anti-doping violations documented
- Unknown long-term safety — longest trial duration 12 weeks
- Gray-market product contamination and mislabeling widely documented
- Potential interactions with hormonal contraceptives and other AR ligands
- No pediatric safety data — avoid in individuals under 18