What Is LGD-4033?
LGD-4033 (Ligandrol, VK5211) is a non-steroidal selective androgen receptor modulator originally developed by Ligand Pharmaceuticals. It was subsequently licensed to Viking Therapeutics for clinical development under the name VK5211.
LGD-4033 is notable for having the highest AR binding affinity (Ki ~1 nM) among the commonly researched SARMs, combined with demonstrated human lean mass effects at extremely low doses (1 mg/day). This potency:dose ratio makes it particularly useful as a research tool for muscle wasting and bone density models.
AR Binding Pharmacology
- AR binding affinity: Ki ~1 nM — approximately 4× stronger than Ostarine and testosterone
- Full agonist in muscle: Produces maximal AR activation in skeletal muscle relative to its affinity
- Partial agonist in prostate: Significantly less prostate stimulation per dose vs testosterone — basis of the ~500:1 A:A ratio in rodent assays
- No aromatization: No estradiol conversion; no estrogen-mediated effects
- No 5α-reduction: No DHT conversion; no DHT-mediated scalp/sebaceous effects
- Oral bioavailability: ~95% in preclinical studies; well-absorbed in human trials
Basaria et al. Phase II Trial (2013)
The Basaria et al. study (published in Journals of Gerontology) is the most-cited primary efficacy data for LGD-4033:
- Design: Randomized, double-blind, placebo-controlled; 76 healthy male subjects (21–50 years), LGD-4033 at 0.1, 0.3, or 1.0 mg/day for 21 days.
- Lean mass: +1.21 kg at 1 mg/day vs placebo after 21 days — statistically significant and dose-dependent. Remarkably, this was achieved at 1 mg — approximately 50× lower than typical steroid doses.
- Muscle strength: Leg press strength trended higher at 1 mg/day (statistically non-significant given short duration and study power).
- Safety markers: PSA unchanged; liver enzymes (ALT, AST) within normal limits; no significant lipid changes; hemoglobin unchanged.
- HPTA: Dose-dependent decrease in total testosterone, free testosterone, and SHBG — confirming HPTA suppression (expected for any AR agonist).
VK5211 Hip Fracture Trial (Viking Therapeutics)
Viking Therapeutics conducted a Phase II trial of LGD-4033 (branded VK5211) in hip fracture rehabilitation (NCT02578095):
- Population: Adults recovering from acute hip fracture surgery
- Doses: 0.5 mg, 1 mg, or 2 mg/day oral for 12 weeks
- Results (2017): Dose-dependent increase in lean body mass; improvements in physical function vs placebo; generally well tolerated
- Clinical significance: Hip fracture rehabilitation is a high-value indication — approximately 30% of hip fracture patients die within one year primarily due to muscle loss and functional decline
- Phase III plans: Viking indicated Phase III interest post Phase II readout. VK5211 remains the most advanced SARM in musculoskeletal development as of 2026.
Pharmacokinetics
| Parameter | LGD-4033 | Notes |
|---|---|---|
| Half-life (humans) | 24–36 hours | Enables once-daily dosing protocols |
| Oral bioavailability | ~95% (preclinical) | High; well-absorbed orally |
| Metabolism | Hepatic (CYP3A4 minor) | Minor CYP involvement; low drug interaction risk |
| Protein binding | >99% | Primarily albumin-bound |
| Detection window | ~3 weeks urine | WADA-relevant for anti-doping research |
HPTA Suppression
Like all AR agonists, LGD-4033 suppresses the hypothalamic-pituitary-gonadal axis via negative feedback. Research context:
- Dose-dependent testosterone and LH suppression confirmed in Basaria et al.
- At 1 mg/day for 21 days: total testosterone fell to ~60% of baseline
- Recovery to baseline was documented within 5 weeks of cessation in Basaria et al.
- HPTA recovery timeline is an important endpoint in SARM research designs studying axis suppression and recovery