LGD-4033 is a 3rd generation non-steroidal oral SARM with a high affinity for the androgen receptor (Ki of ~1 nM). It is currently the second most popular SARM on the market. Unlike testosterone which exerts anabolic effects by the same pathway, LGD-4033 has high selectivity for receptors in skeletal muscle, bone, and connective tissue, with minimal affinity for receptors in the prostate, scalp and skin. It was developed by Ligand Pharmaceuticals to treat conditions such as muscle wasting and osteoporosis without the virilizing side effects of anabolic steroids .
Preclinical primate data showed a significant dose-dependent increase in lean body mass for male and female monkeys during 13 weeks of dosing at either 0.6, 3, 15, or 75 MG/KG of bodyweight . In addition to this, 70% of the increased body mass was retained after a 4 week recovery period. Only the 75mg/kg group stopped treatment after 48 days due to toxicity , which is not a concern because this is significantly higher than the highest dose administered in clinical trials (0.5, 1, and 2mg administered to humans respectively) .
A Phase 1 clinical trial with 76 adult male humans orally administered LGD-4033 at varying doses showed a dose-dependent increase in lean body mass and was well tolerated by all 76 subjects for 21 days [1,2]. Phase 2 clinical trials consisted of 120 patients recovering from hip fracture surgery. The participants either received a placebo, 0.5, 1, or 2mg LGD-4033 over 12 weeks . All doses of LGD-4033 created significant increases in total lean body mass and subjects exhibited dose dependent decreases in mean fat mass. Patients administered LGD-4033 showed improvements in serum procollagen type 1 propeptide (s-P1NP), a marker of bone anabolism, and improvements in 6-minute walk distance as compared to placebo. No significant adverse effects were reported in any of the study groups . Patients were assessed 12 weeks after completion of the trial, at which they maintained the muscle mass that they had gained from the drug .
The promises of increased lean mass and strength coupled with fat loss has made LGD-4033 attractive to athletes. In 2015 Florida Gators quarterback Will Grier was suspended for testing positive for LGD-4033 . This was after his 43lbs of muscle gain, 12 touchdowns, 2 interceptions and a whopping 1202 yards, all in the first half of the season. In 2017 Joakim Noah was banned for twenty games by the NBA for testing positive for LGD-4033 . In 2019 Australian swimmer Shayna Jack teseted positive for LGD-4033  as did Canadian sprint canoeist Laurence Vincent Lapointe. She insists that she did not take supplements on her own and was administered these by the National Team Training Centre .
LGD 4033 Investigational Benefits Summary:
1. Most potent SARM for building muscle tissue
2. Accelerated healing of muscle, bone, and connective tissue post-injury and post-surgery
3. Lean mass gained is generally maintained after cessation of use
1. Basaria et al. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men. The Journals of Gerontology: Series A, Volume 68, Issue 1, January 2013, Pages 87–95.
2. Fragkaki et al. Human in vivo metabolism study of LGD-4033. Drug Test Analysis. Drug Test Anal. 2018 Nov;10(11-12):1635-1645. doi: 10.1002/dta.2512. Epub 2018 Nov 8.
3. “Viking Therapeutics Initiates Phase 2 Trial of VK5211 in Patients Recovering From Hip Fracture.” FierceBiotech. Questex LLC, 03 Nov. 2015. Web. 21 Nov. 2016.
4. Trahan, Kevin (12 October 2015). “Florida starting QB Will Grier suspended for at least 2015 after taking banned substance”. SB Nation. Retrieved 20 October 2015.
5. NBA bans Joakim Noah 20 games for drug violation”. Fox Sports. March 25, 2017.
6. James Maasdorp (July 28, 2019). “Shayna Jack reveals banned substance Ligandrol was behind her doping suspension from swimming”. Australian Broadcasting Corporation. Retrieved July 28, 2019.
7. Canada’s Vincent Lapointe reveals she tested positive for muscle-building substance”. CBC. 20 August 2019.