LGD-4033 (Ligandrol) — Evidence Review

What it is

LGD-4033 is a nonsteroidal selective androgen receptor modulator originally developed by Ligand Pharmaceuticals and later licensed to Viking Therapeutics (as the clinical candidate VK5211). It was investigated for muscle-wasting conditions, recovery from hip-fracture surgery, cachexia, hypogonadism and osteoporosis. It has never received regulatory approval for any indication, and development for most of those uses was discontinued; by 2026 Viking described the VK5211 asset as positioned for partnering rather than active internal Phase 3 development. Despite this, LGD-4033 is widely sold illicitly online and in "bodybuilding"/"research chemical" products, which the FDA classifies as unapproved (and often adulterated) drugs, not dietary supplements.

How it works

Binds the androgen receptor with high affinity and acts as a tissue-selective agonist: it is designed to drive anabolic responses in skeletal muscle and bone while exerting comparatively weaker androgenic activity on tissues such as the prostate and skin. It is nonsteroidal and non-aromatizable. In healthy men, dosing produced dose-dependent gains in lean mass together with dose-dependent suppression of the hypothalamic-pituitary-gonadal axis (falls in total and free testosterone, SHBG, LH and FSH), consistent with androgen-receptor engagement and negative feedback. The mechanism of its liver toxicity is not established but is thought to relate to excessive androgen-receptor engagement, resembling anabolic-steroid cholestasis.

Efficacy — what the human evidence shows

The Institute grades each claimed effect by the strength of the human evidence behind it. Grades are assigned independently for benefit and for harm.

Lean body mass gain in healthy young menProbable

In the only published controlled human trial in healthy men, LGD-4033 produced a dose-dependent increase in lean body mass averaging about 1.21 kg at the 1.0 mg dose over 21 days, with no significant change in fat mass.

Basaria et al. 2013, J Gerontol A Biol Sci Med Sci 68(1):87-95 (PMID 22459616). Randomized, double-blind, placebo-controlled Phase 1, n=76 healthy men aged 21-50, 0.1/0.3/1.0 mg daily x21 days. Surrogate endpoint (DXA lean mass), single short study.

Lean body mass gain in hip-fracture patientsProbable

The Phase 2 VK5211 trial met its primary endpoint: placebo-adjusted increases in total lean body mass of roughly 4.8%, 7.2% and 9.1% (about 1.6, 2.5 and 3.1 kg) at 0.5, 1.0 and 2.0 mg over 12 weeks (p<0.005 to p<0.001).

Viking Therapeutics VK5211 Phase 2, n=108, 12 weeks, top-line results reported Nov 2017 and presented at ASBMR 2018. Surrogate endpoint (DXA lean mass); results in a press-release/conference form, not a peer-reviewed full trial report.

Physical function / mobility (6-minute walk, physical performance battery)Insufficient

In the Phase 2 hip-fracture study, functional measures showed only numerical, non-significant improvement over placebo; these endpoints were exploratory and not powered for significance.

Viking VK5211 Phase 2 secondary/exploratory endpoints (2017-2018). No adequately powered functional-outcome data; program did not advance to Phase 3.

Muscle strengthInsufficient

The 21-day healthy-men study measured muscle strength but did not demonstrate significant strength gains over this short exposure; there is no adequately powered strength/performance data for LGD-4033.

Basaria et al. 2013 (strength assessed; short 21-day intervention, no significant strength benefit reported).

Muscle wasting / cachexia / hypogonadism / osteoporosis (proposed indications)Insufficient

These were proposed therapeutic targets, but no pivotal efficacy trials were completed and development for these indications was discontinued; there is no approved use.

Ligand/Viking development history; per Viking pipeline updates, non-hip-fracture indications were discontinued and VK5211 is positioned for partnering with no active Phase 3.

Safety signals

Harm signals are reported prominently even where the evidence grade is low. Absence of evidence is not evidence of safety.

Testosterone / HPG-axis suppression and adverse lipid shiftsProbable

In the healthy-men RCT (Basaria 2013) LGD-4033 caused dose-dependent suppression of total testosterone and SHBG, together with reductions in HDL cholesterol and triglycerides. Free testosterone and FSH fell significantly only at the highest 1.0 mg dose, and LH was not reported as suppressed. Hormone and lipid measures returned toward baseline by roughly five weeks after stopping; effects of longer or higher-dose use are uncharacterised.

Cholestatic drug-induced liver injury (DILI)Preliminary

PROMINENT HARM SIGNAL: multiple published case reports describe severe cholestatic hepatitis and jaundice after LGD-4033 use, including a 32-year-old man (biopsy-confirmed cholestatic hepatitis after ~10 mg/day for 2 weeks) and a 52-year-old man with peak total bilirubin ~17 mg/dL and ALT 207 U/L after ~3 months of high-dose use. NIH LiverTox notes ligandrol was implicated in the majority of documented SARM-DILI cases; onset is typically weeks to a few months, injury is usually self-limited but prolonged (weeks to months to resolve). This toxicity was NOT captured by the short-duration clinical trials.

Unapproved and frequently adulterated / mislabeled productsPreliminary

LGD-4033 is sold illegally as a 'supplement' or 'research chemical'; the FDA warns these are unapproved drugs with serious safety concerns, and the actual identity and dose of the compound in such products frequently differ from the label, compounding the risk to users.

FDA-flagged serious associations (heart attack, stroke, psychosis, infertility, testicular shrinkage, miscarriage)Insufficient

The FDA lists these serious potential harms for SARM-containing products based on adverse-event reports; a specific causal contribution of LGD-4033 to each is not established, but they are flagged prominently because absence of trial evidence is not evidence of safety.

Human trials on record

Study / registry	Phase	Population	Key result
Basaria et al. 2013 (J Gerontol A Biol Sci Med Sci; PMID 22459616)	Phase 1	76 healthy young men, aged 21-50	Dose-dependent lean body mass gain (+~1.21 kg at 1.0 mg over 21 days, fat mass unchanged); dose-dependent suppression of total/free testosterone, SHBG, LH, FSH, HDL and triglycerides; well tolerated over 21 days with no drug-related serious adverse events (short duration limits safety inference).
VK5211 Phase 2 (Viking Therapeutics)	Phase 2	108 patients recovering from non-elective hip-fracture surgery	Met primary endpoint: placebo-adjusted lean body mass increases ~4.8% to 9.1% (1.6-3.1 kg) across 0.5-2.0 mg over 12 weeks; functional endpoints numerically improved but underpowered; no drug-related SAEs reported. Program was not advanced to Phase 3 and is described as positioned for partnering.

Legal & regulatory status

United States

Not approved by the FDA for any indication. FDA classifies SARM-containing bodybuilding products as unapproved drugs (not lawful dietary supplements) and has issued consumer warnings and warning letters citing risks of liver injury, heart attack and stroke. Sale in supplements is illegal.

Anti-doping (WADA)

Prohibited at all times, in and out of competition, under class S1.2 (Other Anabolic Agents) of the WADA Prohibited List; ligandrol was added to the list in 2018. Multiple athletes have been sanctioned for LGD-4033 metabolites.

Other jurisdictions

Marketed globally as a gray-market 'research chemical' or supplement adulterant despite lacking approval in any major jurisdiction; product content and labeled dose are frequently inaccurate.

The bottom line

LGD-4033 is one of the better-studied SARMs in humans, and the lean-mass signal is real: a 21-day Phase 1 RCT in healthy men and a 12-week Phase 2 trial in hip-fracture patients both showed dose-dependent lean body mass gains. But the evidence stops at short-duration surrogate endpoints (body composition) - there is no demonstrated clinical-outcome benefit, no adequately powered strength/function data, and no regulatory approval anywhere; Viking has effectively shelved active development. Against thin benefit sits a clear harm profile: consistent, dose-dependent testosterone and HDL suppression in the controlled trial, and multiple published case reports of severe cholestatic liver injury (jaundice, high bilirubin) that the short trials never detected. It is banned by WADA at all times and sold only as an unapproved, frequently mislabeled product. This entry is a scientific reference, not a usage recommendation.

References

The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young MenThe Journals of Gerontology: Series A (Basaria et al.), 2013
Viking Therapeutics Announces Positive Top-Line Results From Phase 2 Study of VK5211 in Patients Recovering From Hip FractureViking Therapeutics / PR Newswire, 2017
Viking Therapeutics Presents Results from Phase 2 Study of VK5211 in Patients Recovering from Hip Fracture (ASBMR 2018)Viking Therapeutics Investor Relations, 2018
Ligandrol (LGD-4033)-Induced Liver Injury (case report)ACG Case Reports Journal (Barbara, Dhingra, Mindikoglu), 2020; PMID 32637435
LGD-4033 and a Case of Drug-Induced Liver Injury: Clinical Implications of Off-Label SARM Use in Healthy AdultsCureus (Labban et al.), 2024; 16(9):e69601
Selective Androgen Receptor Modulators (LiverTox chapter)NIH LiverTox / NIDDK, NCBI Bookshelf NBK619971
Certain bodybuilding products put consumers at risk for heart attack, stroke, serious liver damage and more (SARMs safety communication)U.S. Food and Drug Administration
Top 5 Things to Know about LGD-4033U.S. Anti-Doping Agency (USADA)
The Prohibited List (S1 Anabolic Agents, including SARMs)World Anti-Doping Agency (WADA)
SARM use and related adverse events including drug-induced liver injury: analysis of suspected casesEuropean Journal of Clinical Pharmacology, 2023
VK5211 (LGD-4033) pipeline / development statusViking Therapeutics

SARMS Institute Research Desk. Compiled from primary sources. Last updated 20 July 2026.
This review is for education and does not provide medical or legal advice. No SARM is approved for human use.