Vasireddi N, Hahamyan H, Salata MJ, Karns M, Calcei JG, Voos JE, Apostolakos JM
HSS J
Systematic review of 36 studies (35 preclinical, 1 clinical) synthesized BPC-157 evidence in musculoskeletal injuries, highlighting tendon, ligament, and bone healing, but the absence of robust clinical human data.
Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A
Mol Med
Phase 2 study showed that ARA 290 (4 mg/day, 28 days) improved glycated hemoglobin, lipid profile, and neuropathic symptoms in patients with type 2 diabetes.
Klicek R, Kolenc D, Suran J, Drmic D, Brcic L, Aralica G, Sever M, Holjevac J, Radic B, Turudic T, Kokot A, Patrlj L, Rucman R, Seiwerth S, Sikiric P
J Physiol Pharmacol
Comprehensive study demonstrated the effects of BPC-157 on gastrointestinal healing, colonic anastomosis repair, and protection against brain demyelination in rats.
Heij L, Niesters M, Swartjes M, Hoitsma E, Drent M, Dunne A, Grutters JC, Vogels O, Brines M, Cerami A, Dahan A
Mol Med
Double-blind pilot study with 22 patients showed that ARA 290 significantly improved the small fiber neuropathy score in sarcoidosis patients at week 4.
Kandalla PK, Goldspink G, Butler-Browne G, Mouly V
Mech Ageing Dev
Study demonstrated that the MGF-E peptide increased the proliferative lifespan of human satellite cells and promoted activation and fusion of these progenitor cells from donors of different ages.
Zhivotova EY, Fleishman MY, Sazonova EN, Lebed'ko OA, Timoshin SS
Bulletin of Experimental Biology and Medicine
In an experimental model of indomethacin-induced gastropathy, dalargin significantly reduced erosive lesion area, normalized epithelial cell proliferation, and decreased oxidative stress in the gastric mucosa.
Pioneering research demonstrated the effects of BPC-157 on sphincter function and tissue healing, establishing the groundwork for studies on its regenerative properties.
Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH, Rubino D, Sbraccia P, Wadden T, Zeuthen N, Wilding JPH, et al.
N Engl J Med
REDEFINE-1 phase 3 trial with 3,417 adults demonstrated CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg weekly) produced 20.4% weight loss at 68 weeks vs. 3.0% with placebo.
Ji L, Jiang H, Bi Y, Li H, Tian J, Liu D, Zhao Y, Qiu W, Huang C, Chen L, Zhong S, Han J, et al.
N Engl J Med
GLORY-1 phase 3 trial with 610 Chinese adults demonstrated weight loss of up to 14.01% with weekly mazdutide 6 mg over 48 weeks (vs 0.30% placebo), with significant cardiometabolic benefits.
Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu WS, Liu R, Li J, Fernández Landó L, Denning M, Ludwig L, Chen Y, et al.
N Engl J Med
ACHIEVE-1 phase 3 trial demonstrated oral orforglipron reduced HbA1c by 1.2-1.5% and body weight by 4.5-7.6% in adults with early type 2 diabetes over 40 weeks.
Sanyal AJ, Newsome PN, Kliers I, Østergaard LH, Long MT, Kjær MS, Cali AMG, Bugianesi E, Rinella ME, Roden M, Ratziu V, et al.
N Engl J Med
72-week interim analysis of the ESSENCE trial showed semaglutide 2.4 mg achieved MASH resolution without fibrosis worsening in 62.9% vs 34.3%, and fibrosis improvement in 36.8% vs 22.4% (placebo).
Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, Lincoff AM, McGuire DK, Nauck MA, Nissen SE, Sattar N, Zinman B, Zoungas S, et al.
N Engl J Med
SURPASS-CVOT trial with 13,299 patients demonstrated non-inferiority of tirzepatide vs. dulaglutide for MACE (HR 0.92), with metabolic benefits and reduced all-cause mortality in type 2 diabetes and atherosclerotic cardiovascular disease.
Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M, Borlaug BA, et al.
N Engl J Med
SUMMIT trial (n=731) showed tirzepatide reduced the composite risk of cardiovascular death or worsening heart failure by 38% in patients with HFpEF and obesity (HR 0.62; P=0.026).
STEP-HFpEF DM trial demonstrated weekly semaglutide 2.4 mg improved symptoms, physical function, exercise capacity, and produced weight loss in patients with obesity-related HFpEF and type 2 diabetes.
Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, et al.
N Engl J Med
FLOW trial with 3,533 patients with type 2 diabetes and chronic kidney disease demonstrated a 24% reduction in risk of major kidney events and cardiovascular death with weekly semaglutide 1.0 mg (HR 0.76; P=0.0003).
Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, et al.
N Engl J Med
The SURMOUNT-OSA trials showed tirzepatide reduced the apnea-hypopnea index by ~25-29 events/hour vs placebo in adults with moderate-severe obstructive sleep apnea and obesity.
Frias JP, Hsia S, Engel SS, Khanna S, Dunbar SA, Nedelcu L, et al.
Lancet
Phase 2 trial with 383 diabetic patients showed that oral orforglipron reduced HbA1c and body weight comparably or superiorly to injectable dulaglutide.
Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al.
N Engl J Med
Phase 2 trial with 272 obese adults without diabetes showed that oral orforglipron produced weight loss of up to 14.7% in 36 weeks, comparable to injectables.
SELECT trial with 17,604 obese adults without diabetes demonstrated a 20% reduction in major cardiovascular events with semaglutide 2.4 mg (HR 0.80; P<0.001).
Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al.
Lancet
SURMOUNT-2 trial showed weight loss of 12.8% (10 mg) and 14.7% (15 mg) with tirzepatide versus 3.2% with placebo in adults with obesity and type 2 diabetes.
Lau DCW, Erichsen L, Francisco-Ziller N, Johannesen J, Kloverpris S, Krogh P, et al.
Lancet
Phase 2 trial showed that weekly cagrilintide 4.5 mg produced 10.8% weight loss at 26 weeks, surpassing liraglutide 3.0 mg (9.0%) with good tolerability.
Aronne L, Fujioka K, Aroda V, Chen K, Halseth A, Kesty NC, et al.
J Clin Endocrinol Metab
A phase 2 trial with 204 obese adults without diabetes showed that pramlintide produced 3.7% weight loss beyond placebo at 16 weeks, with 31% achieving ≥5%.
Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD
Diabetes Care
The first pivotal exenatide trial demonstrated significant HbA1c reduction and weight loss in type 2 diabetic patients, establishing incretin mimetics.
Hollander PA, Levy P, Fineman MS, Maggs DG, Shen LZ, Strobel SA, et al.
Diabetes Care
A 52-week trial demonstrated that pramlintide 120 mcg reduced HbA1c with weight loss in type 2 diabetics on insulin, without increased severe hypoglycemia.
Argente J, Verge CF, Okorie U, Fennoy I, Kelsey MM, Cokkinias C, Scimia C, Lee HM, Farooqi IS
Lancet Diabetes Endocrinol
VENTURE phase 3 trial in 12 children (2-5 years) with genetic obesity due to POMC, LEPR, or Bardet-Biedl syndrome: 83% achieved BMI Z-score reduction >=0.2 and mean BMI decline ~18%.
Haqq AM, Chung WK, Dolber T, Haws RM, Mitchell JA, Nissen SE, Rees AH, Sethi M, Stewart M, Yuan G, Clément K
Lancet Diabetes Endocrinol
Randomized phase 3 trial with 38 patients showed that 32.3% of adults with Bardet-Biedl syndrome achieved ≥10% weight loss with setmelanotide over 52 weeks.
Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, De Waele K, Farooqi IS, et al.
Lancet Diabetes Endocrinol
Phase 3 trials demonstrated ≥10% weight loss in 80% of patients with POMC deficiency and 45% with LEPR deficiency treated with setmelanotide for 1 year.
Demonstrated that MOTS-c translocates from mitochondria to the nucleus under metabolic stress, acting as a nuclear transcriptional regulator of antioxidant and metabolic genes.
Randomized crossover study in 75 adults with type 1 diabetes demonstrated that intranasal glucagon (3 mg) is non-inferior to intramuscular (1 mg) in reversing insulin-induced hypoglycemia.
Sherr JL, Ruedy KJ, Foster NC, Piché CA, Dulude H, Rickels MR, Tamborlane WV, Bethin KE, DiMeglio LA, Fox LA, Wadwa RP, Schatz DA, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW
Diabetes Care
Pharmacokinetic and pharmacodynamic study in 48 children and adolescents (4-17 years) with type 1 diabetes showed that a single 3 mg dose of intranasal glucagon is effective across the entire pediatric age range.
Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P
Cell Metab
Landmark discovery of MOTS-c as a mitochondrial peptide that regulates metabolism, improves insulin sensitivity, and prevents diet-induced obesity in mice.
Clinical analysis demonstrating that visceral fat reduction with tesamorelin is associated with improved metabolic profile in HIV patients with lipodystrophy.
Barnhart KF, Christianson DR, Hanley PW, Driessen WHP, Bernacky BJ, Baze WB, Wen S, Tian M, et al.
Sci Transl Med
Adipotide induced vascular apoptosis in white adipose tissue of obese monkeys, resulting in 10.6% weight loss in 28 days and improved insulin resistance.
Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM
Cell
Landmark study demonstrated that AICAR administered to sedentary mice for 4 weeks increased exercise endurance by 44%, mimicking the effects of physical training.
Ng FM, Sun J, Sharma L, Libinaki R, Jiang WJ, Gianello R
Horm Res
AOD-9604 reduced body fat in obese mice without affecting blood glucose or IGF-1, confirming its selective lipolytic profile derived from the GH fragment.
Continuous infusion of LR3-IGF-I (120 µg/day) in guinea pigs for 7 days produced significant organ growth (adrenals, gut, kidneys, spleen) without body weight gain, with paradoxical suppression of endogenous IGF.
Tomas FM, Knowles SE, Owens PC, Chandler CS, Francis GL, Read LC, Ballard FJ
Biochemical Journal
Preclinical demonstration that IGF-1 variants, including the Long R3 IGF-1 analog, are approximately 2.5 times more potent than native IGF-1 in reversing dexamethasone-induced catabolism in rats.
Phase 2 trial with 248 Chinese adults demonstrated that mazdutide (dual GLP-1/glucagon agonist) reduced weight by up to 11.7% over 24 weeks versus 1.0% with placebo.
Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, et al.
N Engl J Med
Two phase 3 trials with over 1,270 patients demonstrated that linaclotide significantly improved bowel movement frequency and consistency versus placebo.
Youssef JG, Lavin P, Schoenfeld DA, Lee RA, Lenhardt R, Park DJ, et al.
Crit Care Med
Randomized trial with 196 patients showed that IV aviptadil doubled the probability of survival at 60 days in COVID-19 respiratory failure (OR 2.0; p=0.035).
Kalamkar S, Acharya J, Kolappurath Madathil A, Gajjar V, Divate U, Karandikar-Iyer S, Goel P, Ghaskadbi S
Antioxidants (Basel)
Oral glutathione 500 mg/day for 6 months elevated blood GSH, reduced oxidative DNA damage, and decreased HbA1c in type 2 diabetic patients over 55 years old.
Kuznik BI, Khavinson VKh, Shapovalov KG, Tsybikov NN, Lukyanov SA
Adv Gerontol
Randomized trial with 80 elderly patients with severe COVID-19 showed that Thymalin accelerated recovery, reversed lymphopenia, and halved hospital mortality.
Molecular docking modeling showed that short peptides from the Khavinson school — including EDP (Crystagen, Glu-Asp-Pro) — bind specific DNA sequences (EDP → "agat" sequence), providing structural basis for the epigenetic regulation of gene expression.
Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X
Critical Care
Multicenter trial in 361 severe sepsis patients showed a trend toward reduction in 28-day mortality (26% vs 35%) with thymosin alpha-1, with significant improvement in mHLA-DR expression.
Clinical study in 37 HCV/HIV coinfected patients showed that oral HEP1 (Gepon) as monotherapy reduced HCV viral load by an average of 2 log (~100x), with 27% of patients showing robust reductions up to 7 log.
Comprehensive review on the anti-inflammatory role of α-MSH and MC1R/MC3R receptors, discussing NF-κB inhibition mechanisms and therapeutic potential in inflammatory diseases.
VIP inhalation in patients with primary pulmonary hypertension produced selective pulmonary vasodilation and hemodynamic improvement without systemic side effects.
Clinical study of 6-8 years with 266 elderly subjects showed that Thymalin reduced mortality 2-fold and improved cardiovascular, endocrine, and immune functions.
Dinsmore WW, Gingell C, Hackett G, Kell P, Savage D, Oakes R, Frentz G
BJU Int
Multicenter double-blind study with 236 men showed an erectile response rate of 83.9% with intracavernosal injection of aviptadil (VIP) combined with phentolamine.
Randomized trial in 98 chronic hepatitis B patients showed complete virological response of 40.6% after 26 weeks of thymosin alpha-1, versus 9.4% in controls.
Khavinson VKh, Popovich IG, Linkova NS, Mironova ES, Ilina AR
Molecules
Systematic review demonstrated that short peptides of 2-7 residues, including ovagen (EDL), penetrate the cell nucleus and regulate gene expression via epigenetics.
Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR
Molecules
Systematic review by the Khavinson group consolidating the proposed mechanism by which short peptides (2-7 amino acids) — including dipeptides like the Glu-Asp of Vesilute — penetrate cell nuclei and modulate gene expression via direct interaction with DNA.
Pateyk AV, Baranchugova LM, Rusaeva NS, Obydenko VI, Kuznik BI
Bulletin of Experimental Biology and Medicine
Preclinical study compared the tetrapeptides KEDG (Testagen) and AEDG (Epitalon) in hypophysectomized birds, showing that both partially restore thymus morphology after pituitary disruption.
Clinical trial of 6-8 years with 266 elderly patients showed that thymus peptide bioregulators reduced mortality by 4.1-fold in the combined treatment group.
Lee YI, Lee SG, Jung I, Suk J, Lee MH, Kim DU, Lee JH
International Journal of Molecular Sciences
Pilot clinical study in 22 Asian women showed that topical collagen tripeptide (Gly-Pro-Hyp) for 4 weeks improved wrinkles, elasticity and skin density, and reduced AGE accumulation.
Comprehensive updated review of literature on GHK and GHK-Cu, with Connectivity Map analysis showing the tripeptide modulates 31.2% of human genes at ≥50% expression change, justifying its pleiotropic effects.
Open-label 24-week study in 13 women demonstrated that the decapeptide-12 (Lumixyl) cosmetic system treated facial hyperpigmentation via tyrosinase inhibition, with 38.5% complete clearance and excellent tolerability — including in higher skin phototypes.
Pyo HK, Yoo HG, Won CH, Lee SH, Kang YJ, Eun HC, Cho KH, Kim KH
Archives of Pharmaceutical Research
Korean study showed that the AHK-Cu tripeptide complex stimulates elongation of human hair follicles ex vivo, increases dermal papilla cell proliferation, and reduces apoptosis markers, positioning it as a cosmetic peptide for hair growth.
Double-blind placebo-controlled study in 93 women (35-55 years) demonstrated that topical Matrixyl (pal-KTTKS) over 12 weeks significantly reduced fine wrinkles versus vehicle.
Blanes-Mira C, Clemente J, Jodas G, Gil A, Fernández-Ballester G, Ponsati B, Gutierrez L, Pérez-Payá E, Ferrer-Montiel A
Int J Cosmet Sci
Emulsion with 10% Argireline reduced wrinkles by up to 30% after 30 days, inhibiting neurotransmitter release via the SNARE complex, similar to botulinum toxin.
Katayama K, Armendariz-Borunda J, Raghow R, Kang AH, Seyer JM
Journal of Biological Chemistry
Identification of the KTTKS pentapeptide (residues 212-216 of type I procollagen) as the minimum sequence capable of stimulating fibroblasts to produce collagen I, III and fibronectin — molecular basis of Matrixyl.
Biochemical and Biophysical Research Communications
Loren Pickart's founding work characterizing the glycyl-histidyl-lysine tripeptide (GHK) — base molecule of cosmetic Pal-GHK — as a growth factor isolated from human plasma with effects on hepatocytes.
Tukhovskaya EA, Ismailova AM, Shaykhutdinova ER, Slashcheva GA, Prudchenko IA, Mikhaleva II, Khokhlova ON, Murashev AN, Ivanov VT
Molecules
Intranasal administration of DSIP (120 µg/kg) accelerated motor recovery in rats with focal stroke, demonstrating neuroprotective potential in a cerebral ischemia model.
Alaerts K, Taillieu A, Daniels N, Soriano JR, Prinsen J
Sci Rep
Study demonstrated that intranasal oxytocin amplifies behavioral and neural responses to personally relevant stimuli, regardless of whether they are social or not.
Khavinson V, Linkova N, Kozhevnikova E, Trofimova S
Molecules
Pinealon (EDR) exerts neuroprotective and antiapoptotic effects via MAPK/ERK, regulating gene expression and protein synthesis relevant to Alzheimer's disease.
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M
Front Pharmacol
PE-22-28 demonstrated 500-fold higher affinity for the TREK-1 channel (IC50 0.12 nM), induced neurogenesis in 4 days, and antidepressant activity lasting up to 23 hours.
Muresanu DF, Heiss WD, Hoemberg V, Bajenaru O, Popescu CD, Vester JC, Rahlfs VW, Doppler E, Meier D, Moessler H, Guekht A
Stroke
In patients with moderate-to-severe ischemic stroke, 21 days of Cerebrolysin 30 mL/day combined with rehabilitation significantly improved upper extremity motor function at day 90 compared to placebo, with a safety profile comparable to placebo.
Meta-analysis of 6 randomized controlled trials (n = 597) showed that Cerebrolysin 30 mL/day is significantly superior to placebo on cognition, global clinical change, and combined benefit at 4 weeks and 6 months in mild-to-moderate Alzheimer's disease, with safety comparable to placebo.
Benoist CC, Kawas LH, Zhu M, Bhatt KA, Bhatt SJ, Bhatt JP, Wright JW, Harding JW
J Pharmacol Exp Ther
Oral Dihexa (2 mg/kg) reversed scopolamine-induced cognitive deficit in rats, with procognitive effects mediated by activation of the HGF/c-Met system in the hippocampus.
Kazim SF, Blanchard J, Dai CL, Tung YC, LaFerla FM, Iqbal IG, Iqbal K
Neurobiol Dis
Chronic oral treatment with P021 in 3xTg-AD mice rescued cognitive deficits and reduced tau and amyloid pathology, demonstrating a disease-modifying effect.
Khavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, Kozina L, Arutjunyan A, Boldyrev A
Rejuvenation Res
The tripeptide pinealon reduced reactive oxygen species in a dose-dependent manner in neural cells under oxidative stress, activating ERK 1/2 pathways and proliferation.
Review of the anxiolytic properties of Selank, including neurotransmitter modulation, anti-anxiety effect without sedation, and immunomodulatory action.
Phase 1 study in 24 healthy volunteers demonstrated that intranasal doses of FGLL (25, 100 and 200 mg) are well tolerated, with dose-proportional pharmacokinetics and safety profile adequate for Alzheimer's development.
Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SKS, Ramesh B, Goldspink G, Gorecki DC, Zablocka B
FASEB J
The C-terminal peptide of MGF demonstrated strong autonomous neuroprotective effect in vivo and in vitro, protecting hippocampal neurons in a brain ischemia model.
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E
Nature
Pioneering study in Nature showed that intranasal oxytocin substantially increased interpersonal trust in economic games, without altering the general disposition for risk-taking.
Clinical study demonstrated efficacy of intranasal Semax in treating cerebrovascular disease, with significant neuroprotection and cognitive improvement.
Double-blind study with 14 chronic insomniacs showed that DSIP for 7 nights improved nocturnal sleep from the first dose, achieving efficiency comparable to normal controls.
FOXO4-DRI eliminated more than half of senescent cells in in vitro expanded human chondrocytes without affecting young cells, with potential for joint implant applications.
Research demonstrated that Epitalon activates telomerase and elongates telomeres in multiple tissues, suggesting a direct anti-aging mechanism at the chromosomal level.
Marshall SA, O'Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH
Eur J Pharmacol
B7-33 replicated the vasoprotective functions of serelaxin with anti-fibrotic properties, without increasing cAMP, representing a simplified analog with vascular potential.
Kim HY, Yoon JY, Yun JH, Cho KW, Lee SH, Rhee YM, Jung HS, Lim HJ, et al.
Cell Death Differ
Suppression of the Dvl-CXXC5 interaction by PTD-DBM activated the Wnt pathway, accelerating bone differentiation and increasing mineral density in mice.
Randomized clinical trial in 150 patients compared intrathecal dermorphin (20 µg), intrathecal morphine (500 µg), and intramuscular pentazocine: dermorphin produced deeper and longer-lasting analgesia (43 hours vs 34 h vs 11 h), with an adverse effect profile similar to morphine.
Montecucchi PC, de Castiglione R, Piani S, Gozzini L, Erspamer V
International Journal of Peptide and Protein Research
Seminal study that isolated and characterized dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) from the skin of the frog Phyllomedusa sauvagei, being one of the first vertebrate-derived peptides containing a D-amino acid — a feature responsible for its exceptional opioid potency.
Yen K, Mehta HH, Kim SJ, Lue YH, Hoang J, Guerrero N, Port J, Bi Q, et al.
Aging (Albany NY)
Humanin increased lifespan in C. elegans via daf-16/FOXO, improved metabolic parameters in mice, and showed elevated levels in children of centenarians.
Madhusoodanan V, Patel P, Lima TFN, Gondokusumo J, Lo E, Thirumavalavan N, Lipshultz LI, Ramasamy R
Int Braz J Urol
hCG monotherapy in men with hypogonadal symptoms increased testosterone by 60% (from 362 to 520 ng/dL), with subjective improvement in half of patients.
George JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, Anderson RA
J Clin Endocrinol Metab
Intravenous kisspeptin-10 caused a rapid, dose-dependent increase in LH in healthy men, with maximal response at 1 mcg/kg and increased LH pulsatility.
Pioneering review by the Hadley and Hruby group on melanocortin receptors (MC1R-MC5R) and the role of α-MSH analogs (including NDP-MSH) in pharmacological characterization of the system.
Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA
Obstet Gynecol
Phase 3 RECONNECT trials demonstrated that bremelanotide 1.75 mg SC improved sexual desire and reduced distress in women with hypoactive sexual desire disorder.
Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, et al.
N Engl J Med
Two multicenter trials with 168 patients demonstrated that 16 mg afamelanotide implants increased pain-free sun exposure time in erythropoietic protoporphyria.
Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M, Haddican M, Linkner RV, Lebwohl M
JAMA Dermatol
A trial with 55 patients demonstrated that afamelanotide combined with NB-UV-B accelerated and increased vitiligo repigmentation versus phototherapy alone.
Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R
J Sex Med
Double-blind crossover study in 18 women with sexual arousal disorder showed that intranasal bremelanotide 20 mg significantly increased sexual desire.
A double-blind study in 20 men with erectile dysfunction showed that MT-II induced erection in 17 of 20 participants without sexual stimulus, with increased desire in 68%.
Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME
Life Sci
A phase I pilot study in 3 volunteers demonstrated that subcutaneous Melanotan-II induced visible tanning at low doses, confirming melanotropic activity in humans.
5-Amino-1MQ, a selective membrane-permeable NNMT inhibitor, reduced body weight, white adipose tissue mass, and plasma cholesterol in obese mice without affecting food intake or causing adverse effects.
Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB
Nature
Mice with NNMT knockdown in adipose tissue and liver resisted diet-induced obesity via increased SAM, NAD+, and lipid oxidation gene expression — validating NNMT as a therapeutic target for obesity and type 2 diabetes.
Seminal study that identified GLP-1(7-37) as the bioactive fragment of the glucagon gene: it potently stimulated glucose-dependent insulin secretion in perfused rat pancreas at concentrations as low as 5 × 10⁻¹¹ M.
Genomic analysis demonstrated that GHK-Cu modulates more than 4,000 genes involved in tissue repair, anti-inflammatory defense, and cellular regeneration.
Review demonstrated that GHK modulates more than 4,000 human genes, stimulating collagen synthesis and skin regeneration, with levels that decline with age.
Pirola I, Cappelli C, Delbarba A, Scalvini T, Agosti B, Assanelli D, Bonetti A, Castellano M
Fertil Steril
Case report showed that a single dose of triptorelin (100 mcg) restored normal testosterone within 1 month in a man with post-anabolic steroid hypogonadism.
Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr
J Clin Endocrinol Metab
Study of 76 men treated with pulsatile GnRH for 12-24 months showed that prior pubertal development predicts normal testicular volume (92%) and spermatogenesis.
Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK
Molecular Therapy
First clinical trial of follistatin-344 gene therapy (AAV1.CMV.FS344) injected into the quadriceps of 6 patients with Becker muscular dystrophy: improvements up to 125 meters on the 6-minute walk test, reduced fibrosis, and increased muscle fiber size, with no serious adverse events.
X-ray crystallography study revealed that two follistatin molecules wrap around activin A blocking both type I and type II receptor binding sites, with the FS-315 form being the main serum isoform neutralizing the TGF-β pathway.
Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O
Wound Repair Regen
Clinical trial with 34 patients showed that topical LL-37 accelerated healing of chronic venous ulcers by up to 6-fold compared to placebo, with good safety.
Carretero M, Escámez MJ, García M, Duarte B, Holguín A, Retamosa L, Jorcano JL, Del Río M, Larcher F
J Invest Dermatol
LL-37 promoted wound healing in vitro and in vivo via activation of keratinocyte migration and actin cytoskeleton remodeling through EGFR transactivation.
Heilborn JD, Nilsson MF, Kratz G, Weber G, Sørensen O, Borregaard N, Ståhle-Bäckdahl M
J Invest Dermatol
LL-37 proved essential in wound healing, with peak expression at 48h after injury. Chronic ulcers showed low levels, suggesting a role in re-epithelialization.
Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D
New England Journal of Medicine
Multicenter randomized VASST trial (n = 778) compared low-dose vasopressin (0.01–0.03 U/min) with norepinephrine in septic shock patients: no difference in overall 28-day mortality, but potential benefit in patients with less severe shock (26.5% vs 35.7%, p = 0.05).
European randomized trial (n = 1186) compared vasopressin (40 IU) with epinephrine (1 mg) in out-of-hospital CPR: similar outcomes in ventricular fibrillation, but vasopressin superior in asystole (survival to hospital discharge 4.7% vs 1.5%, p = 0.04).
2-year randomized trial in 65 elderly subjects (60-81 years) demonstrated that oral MK-677 increased lean mass by 1.1 kg versus 0.5 kg loss with placebo, with no corresponding improvement in functional strength.
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA
J Clin Endocrinol Metab
CJC-1295 produced dose-dependent increases in GH (2-10x for 6+ days) and IGF-I (1.5-3x for 9-11 days) in healthy adults with no serious adverse events.
Berlanga J, Cibrian D, Guillen I, Freyre F, Alba JS, Lopez-Saura P, Merino N, Aldama A, Quintela AM, Triana ME, Montequin JF, Ajamieh H, Urquiza D, Ahmed N, Guillen G
Clin Sci (Lond)
GHRP-6 pretreatment reduced hepatic and intestinal ischemia/reperfusion damage by 50-85%, demonstrating potent cytoprotective effects.
Continuous GHRP-2 infusion for 30 days in elderly subjects tripled pulsatile GH secretion on day 1 and sustainably elevated IGF-I and IGFBP-3 without adverse effects.
Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM
Int J Obes Relat Metab Disord
Chronic treatment with the C-terminal fragment of hGH reduced weight gain and increased fat oxidation in obese mice, without hyperglycemia or effects on insulin.
AOD9604 reduced weight gain in obese mice without competing for the GH receptor or inducing cell proliferation, demonstrating a superior safety profile compared to hGH.
Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H
Growth Horm IGF Res
Ipamorelin administered to hypophysectomized rats induced longitudinal bone growth and increased epiphyseal plate width, demonstrating anabolic effects on bone.
Across three double-blind trials with 187 elderly subjects (≥65 years), oral MK-677 increased IGF-1 by 55-94% and elevated osteocalcin by 29.4%, demonstrating an effect on bone formation markers.
Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH
Eur J Endocrinol
First characterization of ipamorelin as a selective GH secretagogue, with potent GH release without affecting cortisol, prolactin, or other pituitary hormones.
Open-label study in 8 prepubertal short-stature children (4-11 years) treated with intranasal hexarelin 60 µg/kg three times daily for up to 8 months, with growth velocity increase from 5.3 to 8.3 cm/year.
Imbimbo BP, Mant T, Edwards M, Amin D, Dalton N, Boutignon F, Lenaerts V, Wüthrich P, Deghenghi R
European Journal of Clinical Pharmacology
Double-blind placebo-controlled study in 12 adult volunteers demonstrated that intravenous hexarelin (0.5-2 µg/kg) raises plasma GH in a dose-dependent manner, with Cmax of 55 ng/mL at the highest dose and half-life of ~55 min.
Felberbaum RE, Albano C, Ludwig M, Riethmüller-Winzen H, Grigat M, Devroey P, Diedrich K
Human Reproduction
Phase III multicenter study in 346 women showed that cetrorelix (0.25 mg/day) starting on stimulation day 6 with HMG effectively suppresses premature LH surge (0.9% incidence), achieving 24% ongoing clinical pregnancy per transfer and low severe OHSS (0.6%).
Gonzalez-Barcena D, Vadillo-Buenfil M, Cortez-Morales A, Fuentes-Garcia M, Cardenas-Cornejo I, Comaru-Schally AM, Schally AV
Urology
Cetrorelix as monotherapy in 5 patients with advanced prostate cancer and paraplegia from cord compression produced immediate testosterone suppression, walking recovery in all patients within 3 months, and gradual PSA decline — without the flare-up associated with LHRH agonists.