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Igf1.8
IGF-1 LR3 Research
Mostly mechanism / observationalLimited safety
8 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most IGF-1 LR3 studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality studies published 2003–2025.
Based on 8 studies
Confidence
Low
By outcome
Lean body mass & muscle growth
Mostly mechanism / observational5 studies
Muscle strength & power
Mostly mechanism / observational4 studies
Glucose & metabolic
Too few graded studies2 studies
Active research area
5 studies in the last 5 years
200320142025
1Animal2022
Experimental infusion of an IGF-1 analog, human recombinant LR3 IGF-1, into late gestation fetal sheep increased fetal organ growth and skeletal muscle myoblast proliferation.
Stremming J, White A, Donthi A, Batt DG, Hetrick B, Chang EI, Wesolowski SR, Seefeldt MB, McCurdy CE, Rozance PJ, Brown LD. · Front Physiol (2022)
Directly on the LR3 analog: human recombinant LR3 IGF-1 infused into late-gestation fetal sheep increased organ growth and stimulated skeletal-muscle myoblast proliferation
A sheep-specific IGF-1 (developed to overcome LR3's limitations) increased growth of heart, kidney, spleen, and adrenal glands and stimulated myoblast proliferation
This is fetal-animal data showing organ overgrowth alongside muscle effects — not a human muscle-building trial
IGF-1 LR3 infusion for 1 wk into fetal sheep lowers insulin concentrations and reduces fetal GSIS.
White A, Stremming J, Boehmer BH, Chang EI, Jonker SS, Wesolowski SR, Brown LD, Rozance PJ. · Am J Physiol Endocrinol Metab (2021)
On the LR3 analog specifically: a 1-week IGF-1 LR3 infusion into late-gestation fetal sheep lowered plasma insulin and glucose and reduced glucose-stimulated insulin secretion
Impaired insulin secretion persisted in isolated fetal islets, indicating an intrinsic islet defect from LR3 exposure
Describes LR3 as 'an analog of IGF-1 with low affinity for the IGF binding proteins and high affinity for the IGF-1 receptor'
In male 5XFAD mice, IN LR3-IGF-1 treatment improved body composition, but did not significantly alter cognitive symptoms, as assessed by multiple assays.
Engel MG, Narayan S, Cui MH, Branch CA, Zhang X, Gandy SE, Ehrlich M, Huffman DM. · J Alzheimers Dis (2025)
Directly tests the LR3 analog (intranasal LR3-IGF-1) over 7 months in an Alzheimer's mouse model
Improved body composition and remodeled amyloid plaques (fewer filamentous, more inert plaques; less low-molecular-weight Aβ oligomer)
Critically, it failed to preserve cognitive function or memory — the authors conclude the data 'do not support LR3 as a monotherapy'
LR3 IGF-1 skeletal muscle had higher myoblast proliferation (P < 0.05). In summary, LR3 IGF-1 infusion for 1 wk into late gestation fetal sheep increased the weight of some fetal organs.
Stremming J, Heard S, White A, Chang EI, Shaw SC, Wesolowski SR, Jonker SS, Rozance PJ, Brown LD. · Am J Physiol Endocrinol Metab (2021)
Directly on the LR3 analog: a 1-week intravenous LR3 IGF-1 infusion into late-gestation fetal sheep increased fetal heart, adrenal-gland, and spleen weights and raised skeletal-muscle myoblast proliferation
Insulin concentrations were lower with LR3 IGF-1 — reinforcing the hypoglycemia/insulin-suppression signal seen in the other fetal-sheep work
Organ growth occurred without increased placental blood flow or nutrient transfer; umbilical amino-acid uptake and fetal amino-acid concentrations were actually lower
Both AG1478 treatment and EGFR silencing also suppress proliferation stimulated by LR3-IGF-1 (an IGF1 analogue that binds normally to the insulin-like growth factor receptor (IGFR)-1 but has little or no affinity for IGF binding proteins) in cultured BSCs.
Reiter BC, Kamanga-Sollo E, Pampusch MS, White ME, Dayton WR. · Domest Anim Endocrinol (2014)
Uses LR3-IGF-1 as a defined IGF-1-receptor agonist to stimulate proliferation of cultured bovine satellite cells (muscle stem cells)
Confirms the analog's defining pharmacology: binds the IGF-1 receptor normally but has little or no affinity for IGF-binding proteins
LR3-IGF-1-stimulated satellite-cell proliferation was suppressed by EGFR inhibition/silencing, implicating EGFR cross-talk
In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three- to five-fold. The blockade of either ERK or PI3K signaling... completely abolished BrdU uptake stimulated by LR3 IGF-1.
We report here the development of a novel covalent conjugate that contains the antifolate drug methotrexate coupled to an engineered variant of insulin-like growth factor-1 (IGF-1), long-R3-IGF-1, which was designed to target methotrexate to tumor cells that overexpress the membrane IGF-1 receptor.
Uses long-R3-IGF-1 (the LR3 analog) specifically because the IGF-1 receptor is overexpressed on many cancer cells — illustrating the IGF-1-axis/cancer link directly relevant to LR3's theoretical risk
The LR3-IGF-1–methotrexate conjugate bound IGF-1-receptor-overexpressing MCF7 breast cancer cells with high affinity
Targeting the IGF-1 receptor delivered chemotherapy to tumors more effectively than free drug in mouse xenografts