IGF-1 LR3 dosing & administration

Prelle K, Stojkovic M, et al. · 2001

This foundational study demonstrated that LR3 IGF-I has dramatically reduced binding to IGF binding proteins compared to regular IGF-1, explaining why it remains active in the bloodstream much longer and has greater bioavailability for tissue effects.

Sundgren NC, Giraud GD, et al. · 2003

Researchers found that Long R3 IGF-I stimulates cell proliferation (hyperplasia) through both ERK and PI3K signaling pathways—this explains the unique ability of IGF-1 to create new cells, not just make existing cells bigger.

Boes M, Dake BL, et al. · 2003

This study showed that LR3 IGF-I can bypass IGF binding proteins that normally sequester IGF-1, demonstrating why LR3 has greater bioactivity—it reaches target tissues more effectively than native IGF-1.

Levolger S, Wiemer EAC, et al. · 2019

LR3 IGF-I treatment effectively limited muscle mass loss in a cancer cachexia model, demonstrating its potent anti-catabolic effects and ability to preserve muscle tissue under conditions that normally cause severe muscle wasting.

Lu Z, Liu N, et al. · 2023

Purified LR3 IGF-1 displayed excellent bioactivity for cell proliferation comparable to standard IGF-1, confirming that the molecular modifications preserve its biological function while extending its active lifespan.

Ballard FJ, Walton PE, Bastian S, Tomas FM, Wallace JC, Francis GL · 1993

In direct comparisons, IGF-I bound IGF-binding proteins (IGFBP-3, IGFBP-4 and total rat plasma IGFBPs) with approximately 1000-fold higher affinity than LR3 IGF-I, and the weaker binding gave LR3 IGF-I 5-10 times greater potency in cultured myoblasts and 6 times greater growth potency in rats. The same study found that LR3 IGF-I was cleared from rat plasma more rapidly than IGF-I, precisely because it does not associate with binding proteins.

Tomas FM, Walton PE, Dunshea FR, Ballard FJ · 1997

In pigs and marmoset monkeys, IGF-I variants that bind poorly to IGF-binding proteins, including LR3 IGF-I, lowered blood glucose 2- to 3-fold more potently than native IGF-I and kept glucose suppressed over a much longer period, giving a roughly 4- to 8-fold larger cumulative hypoglycaemic effect.

Bilan PJ, Mitsumoto Y, Ramlal T, Klip A · 1992

In muscle cells, IGF-I raised glucose uptake within about 10 minutes by moving glucose transporters (GLUT1 and GLUT4) to the cell surface, with no new protein synthesis required. Longer exposure additionally increased the amount of transporter the cells made.

Ipsen Biopharmaceuticals, Inc. · 2025

The FDA label for mecasermin (recombinant human IGF-1) reports hypoglycemia in 30 of 71 trial subjects (42%), including 5 severe episodes and 4 hypoglycemic seizures, and directs that each dose be given shortly before or after (plus or minus 20 minutes) a meal or snack, and not given if the meal is skipped.

Le Roith D, Bondy C, Yakar S, Liu JL, Butler A · 2001

This review describes the growth hormone/IGF-1 axis, in which pituitary GH stimulates the liver to produce IGF-1 that supplies most of the IGF-1 in the bloodstream. It also reviews evidence that IGF-1 made locally in other tissues contributes to growth, since mice lacking liver IGF-1 still grow normally despite a large drop in circulating IGF-1.

Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ · 2001

IGF-1 enlarged cultured muscle fibers through PI3K/Akt signaling, with Akt driving growth by activating the mTOR pathway and by inhibiting GSK3, both routes previously linked to increased protein synthesis.

Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M, Yancopoulos GD, Glass DJ · 2004

IGF-1 signaling through PI3K/Akt blocked production of the muscle-wasting ubiquitin ligases MAFbx/atrogin-1 and MuRF1 by inhibiting FOXO transcription factors, which is the route by which IGF-1 suppresses muscle protein breakdown.

Chakravarthy MV, Abraha TW, Schwartz RJ, Fiorotto ML, Booth FW · 2000

IGF-I kept skeletal muscle satellite cells dividing for at least five population doublings beyond the normal limit, acting through PI3K/Akt signaling and reduced p27(Kip1) to speed passage through the G1/S checkpoint.

Pelosi L, Giacinti C, Nardis C, Borsellino G, Rizzuto E, Nicoletti C, Wannenes F, Battistini L, Rosenthal N, Molinaro M, Musaro A · 2007

Mice engineered to express IGF-1 in muscle repaired injured muscle faster than normal mice, with a quicker drop in pro-inflammatory cytokines and less fibrous scarring. The effect was measured after experimental injury in mice, not after training in humans.

Thompson JL, Butterfield GE, Marcus R, Hintz RL, Van Loan M, Ghiron L, Hoffman AR · 1995

Sixteen healthy elderly women received recombinant human IGF-1 or GH for four weeks. Fat mass fell in all groups, and lean body mass and nitrogen retention rose significantly in the high-dose IGF-1 and GH groups. The high dose also produced side effects including headaches and joint swelling, while the low IGF-1 dose was well tolerated.

Clemmons DR, Moses AC, Sommer A, Jacobson W, Rogol AD, Sleevi MR, Allan G · 2005

In 52 patients with type 2 diabetes, recombinant IGF-1 given with its binding protein cut insulin requirements by 54-82% and lowered fasting glucose by 32-37%. Side effects including edema, jaw pain and arthralgia occurred at a frequency of 4%.

Tomas FM, Knowles SE, Owens PC, Chandler CS, Francis GL, Read LC · 1992

Compared LR3 IGF-I with native IGF-1 in rats: LR3 IGF-I binds IGF binding proteins far more weakly and binds the type 1 IGF receptor with roughly 3-fold lower affinity than native IGF-1, yet is more potent in vivo because less of it is sequestered by binding proteins.