Chapter 2.3

Evidence Database & Research

Curated peer-reviewed research with clinical relevance annotations for healthcare providers

Clinical

Research

Evidence-Based

References

Studies Indexed

Level A Studies

RCTs & Meta-Analyses

Key Studies

Showing 43 of 43 studies

Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM, et al. • New England Journal of Medicine (2023)

RCT

Level A

Retatrutide

n = 338

PMID: 37396564

Key Findings

Retatrutide (GLP-1/GIP/glucagon agonist) produced dose-dependent weight loss up to 24.2% at 48 weeks (12 mg)
Superior to placebo and comparable/superior to dual agonists; low hypoglycemia risk
Clinically meaningful glucose-lowering and cardiorenal risk reduction

Clinical Relevance

Result: retatrutide (GLP-1/GIP/glucagon) up to 24.2% weight loss at 48 weeks. See PMID: 37396564

Limitations

Phase 2; long-term and post-approval data still emerging.

The Mitochondrially Targeted Peptide Elamipretide (SS-31) Improves ADP Sensitivity in Aged Mitochondria by Increasing Uptake Through the Adenine Nucleotide Translocator

Siegel MP, et al. • Antioxidants & Redox Signaling (2023)

In Vitro

Level B

SS-31

PMID: 37462785

Key Findings

SS-31 binds cardiolipin, improves ANT function and ATP production; reduces mitochondrial ROS
MMPOWER-3 RCT in primary mitochondrial myopathy; heart failure and kidney disease trials ongoing
Well tolerated; supports use in mitochondrial and repair protocols

Clinical Relevance

Result: SS-31 (elamipretide) mitochondria-targeted; supports mitochondrial dysfunction. See PMID: 37462785

Limitations

Clinical approval path ongoing; much evidence from mechanistic and phase 2 trials.

Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)

Jastreboff AM, Aronne LJ, et al. • New England Journal of Medicine (2022)

RCT

Level A

Tirzepatide

n = 2,539

PMID: 35658024

Key Findings

15mg dose: 22.5% mean weight loss at 72 weeks
10mg dose: 21.4% weight loss
5mg dose: 16.0% weight loss
Superior to semaglutide in head-to-head comparisons

Clinical Relevance

Study result: dual GIP/GLP-1 mechanism; superior weight loss vs GLP-1 alone. See PMID: 35658024

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial

Comninos AN, et al. • JAMA Network Open (2022)

RCT

Level B

Kisspeptin

n = 32

PMID: 36287566

Key Findings

Kisspeptin-54 triggered egg maturation in IVF; intranasal kisspeptin rapidly stimulates gonadotropin release
RCT in hypoactive sexual desire disorder; kisspeptin modulates reproductive axis and libido
Pulsatile kisspeptin trialled in hypogonadotropic hypogonadism

Clinical Relevance

Result: Kisspeptin stimulates gonadotropin release; supports fertility and hypogonadism. See PMID: 36287566

Limitations

Larger phase 3 and long-term data still limited.

Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

Wilding JPH, Batterham RL, et al. • New England Journal of Medicine (2021)

RCT

Level A

Semaglutide

n = 1,961

PMID: 33567185

Key Findings

14.9% mean weight loss at 68 weeks vs 2.4% placebo
86.4% achieved ≥5% weight loss
69.1% achieved ≥10% weight loss
Significant improvements in cardiometabolic risk factors

Clinical Relevance

Result: semaglutide 2.4mg weekly highly effective for obesity. NNT ~2 for clinically meaningful weight loss. See PMID: 33567185

Limitations

GI side effects common. Long-term data beyond 68 weeks still emerging.

Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells

Khavinson VKh, Linkova NS, et al. • Biology Bulletin Reviews (2021)

Clinical

Level B

Thymalin

PMID: 33237528

Key Findings

Thymalin (polypeptide complex from calf thymus) regulates immune function and hematopoiesis
Long-term trial in 266 elderly: reduced acute respiratory disease incidence 2.0–2.4× and mortality 2.0–2.1× vs control
Regulates gene expression, cytokine production, and cell differentiation; minimal side effects

Clinical Relevance

Result: Thymalin reduced respiratory disease incidence and mortality 2× in elderly. See PMID: 33237528

Limitations

Much data from Russian literature; more Western RCTs would strengthen evidence.

Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model

Sochacki KA, et al. • Antimicrobial Agents and Chemotherapy (2021)

Animal

Level B

LL-37

0PMID: 34680791

Key Findings

Human cathelicidin LL-37 reduced MRSA burden and improved wound healing in surgical wound model
LL-37 effective against polymicrobial infected wounds; broad-spectrum antimicrobial
Only human cathelicidin; expressed by neutrophils and epithelial cells; innate immunity

Clinical Relevance

Result: LL-37 antimicrobial peptide; membrane disruption; wound-healing and gut applications. See PMID: 34680791

Limitations

Key evidence in animal models; topical/systemic human trials limited.

AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in APP/PS1 Mouse via PI3K/AKT

Sun Y, et al. • Brain Sciences (2021)

Animal

Level B

Dihexa

0PMID: 34827486

Key Findings

Dihexa rescued cognitive impairment and memory in APP/PS1 Alzheimer model
PI3K/AKT pathway; hepatocyte growth factor/c-Met activation; synaptogenic
Orally bioavailable; crosses BBB; angiotensin IV analog

Clinical Relevance

Result: Dihexa improved cognition and memory in AD model; procognitive/synaptogenic. See PMID: 34827486

Limitations

Preclinical; human trials limited.

BPC 157 and Tendon Healing: Systematic Review

Gwyer D, Wragg NM, Wilson SL • Journal of Orthopaedic Surgery and Research (2019)

Review

Level B

BPC-157

PMID: 31399107

Key Findings

Consistent promotion of tendon healing in animal models
Enhanced collagen organization
Increased VEGF expression and angiogenesis
Anti-inflammatory effects documented

Clinical Relevance

Preclinical: tendon healing, collagen organization, VEGF. Human RCTs limited. See PMID: 31399107

Limitations

Most evidence from animal studies. Human clinical trials limited.

Bremelanotide for Hypoactive Sexual Desire Disorder in Women (RECONNECT)

Kingsberg SA, et al. • Obstetrics & Gynecology (2019)

RCT

Level A

PT-141

n = 1,247

PMID: 31135757

Key Findings

Significant increase in satisfying sexual events
Improved sexual desire scores
Reduced distress related to low desire
Effects seen as early as first dose

Clinical Relevance

FDA-approved for premenopausal HSDD. Result: increased satisfying sexual events. See PMID: 31135757

BPC 157 and Gastrointestinal Protective Effects

Sikiric P, et al. • Current Pharmaceutical Design (2018)

Review

Level B

BPC-157

PMID: 29589535

Key Findings

Protection against NSAID-induced GI damage
Accelerated healing of gastric ulcers
Beneficial effects on inflammatory bowel conditions
Oral bioavailability demonstrated

Clinical Relevance

Result: oral BPC-157 GI protection, gastric ulcer healing; oral bioavailability shown. See PMID: 29589535

Limitations

Human dose-finding studies needed. Optimal oral dosing unclear.

Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

Yen K, et al. • Scientific Reports (2018)

Cohort

Level B

Humanin

0PMID: 30242290

Key Findings

Humanin administration improved cognition in aged mice
SNP in humanin-coding region associated with accelerated cognitive aging in older adults
Circulating humanin decreases with age; mitochondrial-derived peptide

Clinical Relevance

Result: Humanin neuroprotective; associated with cognitive aging in humans. See PMID: 30242290

Limitations

Observational human data; causal trials limited.

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

Holman RR, et al. • New England Journal of Medicine (2017)

RCT

Level A

Exenatide

n = 14,752

PMID: 29182939

Key Findings

EXSCEL: exenatide once-weekly noninferior to placebo for CV death, MI, stroke (HR 0.91)
14% lower all-cause mortality with exenatide vs placebo (6.9% vs 7.9%)
Median follow-up 3.2 years; 73% had prior CVD; established CV safety

Clinical Relevance

Result: exenatide once-weekly CV safe in T2D; noninferiority for MACE; potential mortality benefit. See PMID: 29182939

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Baar MP, et al. • Cell (2017)

Animal

Level B

FOXO4-DRI

0PMID: 28340342

Key Findings

FOXO4-DRI interferes with FOXO4-p53 interaction; induces apoptosis in senescent cells
Restored fitness, fur density, and kidney function in aged and doxorubicin-treated mice
Proof-of-concept for senolytic peptide; human trials limited

Clinical Relevance

Result: FOXO4-DRI targeted senolysis; improved healthspan in preclinical models. See PMID: 28340342

Limitations

Preclinical; human safety and efficacy data limited.

Cerebrolysin in Patients with Mild to Moderate Dementia: Meta-Analysis

Gauthier S, Proaño JV, et al. • Dementia and Geriatric Cognitive Disorders (2015)

Meta-Analysis

Level A

Cerebrolysin

n = 1,245

PMID: 26227422

Key Findings

Significant improvement in global clinical function (CGI)
Cognitive benefits measured by ADAS-cog
Effects maintained at 6-month follow-up
Good safety profile in elderly patients

Clinical Relevance

Level A evidence: Cerebrolysin for mild-moderate dementia. Benefit in subjects non-responsive to cholinesterase inhibitors. See PMID: 26227422

GHK Peptide as a Natural Modulator of Gene Expression in Regenerative Medicine

Pickart L, Vasquez-Soltero JM, Margolina A • BioMed Research International (2015)

Review

Level B

GHK-Cu

PMID: 6481226

Key Findings

GHK-Cu naturally declines with age
Activates 31.2% of human genes (>50% change)
Stimulates collagen, elastin, and glycosaminoglycans
Promotes nerve and blood vessel growth

Clinical Relevance

Result: GHK-Cu activates 31.2% of human genes; collagen, elastin, nerve/vessel growth. See PMID: 6481226

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

Lee C, et al. • Cell Metabolism (2015)

Animal

Level B

MOTS-c

0PMID: 26071498

Key Findings

MOTS-c (16-aa, mitochondrial 12S rRNA) targets skeletal muscle via folate-AMPK pathway
Prevented age-dependent and diet-induced insulin resistance and obesity in mice
Circulating MOTS-c decreases with aging; lower in T2D; potential senotherapeutic role

Clinical Relevance

Result: MOTS-c prevented insulin resistance and obesity in mice; folate-AMPK pathway. See PMID: 26071498

Limitations

Key evidence in rodents; human RCTs still limited.

ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes

Brines M, et al. • Molecular Medicine (2015)

RCT

Level B

ARA-290

n = 74

PMID: 25387363

Key Findings

ARA-290 (innate repair receptor agonist) improved neuropathic symptoms and metabolic control in T2D
Improved corneal nerve fiber density and PainDetect scores; no hematopoietic effects
Phase 2 sarcoidosis neuropathy trials showed significant pain relief and QoL improvement

Clinical Relevance

Result: ARA-290 improved metabolic control and neuropathic symptoms in T2D subjects. See PMID: 25387363

Limitations

Larger phase 3 and long-term data still limited.

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Pi-Sunyer X, et al. • New England Journal of Medicine (2015)

RCT

Level A

Liraglutide

n = 3,731

PMID: 26132939

Key Findings

3.0 mg liraglutide daily: 8.4 kg mean weight loss at 56 weeks vs 2.8 kg placebo
63.2% achieved ≥5% weight loss vs 27.1% placebo; 33.1% achieved ≥10% vs 10.6%
Improvements in cardiometabolic risk factors; nausea and constipation most common AEs

Clinical Relevance

Result: liraglutide 3 mg daily effective for weight management in obesity; FDA-approved (Saxenda). See PMID: 26132939

Cerebrolysin in Acute Ischemic Stroke: CASTA Trial

Heiss WD, Brainin M, et al. • Stroke (2012)

RCT

Level B

Cerebrolysin

n = 1,070

PMID: 22343647

Key Findings

Improved motor function at 90 days in moderate strokes
Significant benefit in NIHSS 8-15 subgroup
Earlier treatment associated with better outcomes
Safe with standard stroke care

Clinical Relevance

Result: adjunctive therapy in moderate acute ischemic stroke; benefit when started early. See PMID: 22343647

Limitations

Primary endpoint not met in ITT analysis. Benefits seen in pre-specified subgroups.

Effect of Teriparatide on Bone Mineral Density and Fracture in Postmenopausal Osteoporosis: Meta-Analysis of RCTs

Nieves JW, et al. • Osteoporosis International (2012)

Meta-Analysis

Level A

Teriparatide

n = 2,388

PMID: 22257045

Key Findings

Eight RCTs: teriparatide increased spine and hip BMD vs placebo/controls
Reduced vertebral and nonvertebral fracture risk in postmenopausal osteoporosis
FDA-approved PTH(1-34) anabolic; intermittent dosing builds bone

Clinical Relevance

Result: teriparatide meta-analysis; improved BMD and fracture risk in osteoporosis. See PMID: 22257045

Afamelanotide, an Agonistic Analog of α-MSH, in Dermal Phototoxicity of Erythropoietic Protoporphyria

Harms J, et al. • Expert Opinion on Investigational Drugs (2010)

Case Series

Level C

Melanotan 1

n = 5

PMID: 21073357

Key Findings

Afamelanotide (MT-1) increased light tolerance and melanin in EPP patients
α-MSH analog; induces epidermal melanin; FDA-approved implant for EPP (Scenesse)
Tanning and photoprotection; different from MT-II (libido/tanning)

Clinical Relevance

Result: Melanotan 1 (afamelanotide) photoprotection in EPP; FDA-approved for EPP. See PMID: 21073357

Limitations

Small series; EPP is rare; off-label tanning use not approved.

A Randomized Controlled Trial of Intranasal Oxytocin as an Adjunct to Exposure Therapy for Social Anxiety Disorder

Guastella AJ, et al. • Psychoneuroendocrinology (2009)

RCT

Level B

Oxytocin

n = 25

PMID: 19246160

Key Findings

Intranasal oxytocin combined with exposure therapy reduced social threat perception
Improved encoding of positive social cues and communication processes
Small sample; oxytocin effects context-dependent in anxiety populations

Clinical Relevance

Result: intranasal oxytocin as adjunct to exposure therapy may support social anxiety treatment. See PMID: 19246160

Limitations

Small RCT; replication and larger trials needed.

Selank in Generalized Anxiety: Clinical Trial

Zozulia AA, et al. • Bulletin of Experimental Biology and Medicine (2008)

RCT

Level B

Selank

n = 62

PMID: 19504360

Key Findings

Significant reduction in anxiety scores
Comparable efficacy to phenazepam (benzodiazepine)
No sedation or cognitive impairment
No dependence or withdrawal observed

Clinical Relevance

Result: anxiety reduction comparable to phenazepam; no sedation or dependence. See PMID: 19504360

Melanocortin-Derived Tripeptide KPV Has Anti-Inflammatory Potential in Murine Models of Inflammatory Bowel Disease

Kokot A, et al. • Inflammatory Bowel Diseases (2008)

Animal

Level C

KPV

0PMID: 18092346

Key Findings

KPV (α-MSH 11-13) reduced inflammatory infiltrates and MPO in DSS-induced colitis; earlier recovery and weight regain
Anti-inflammatory effect distinct from classic melanocortin receptors; inhibits IL-1β
Rescued MC1R-deficient mice from lethal DSS colitis

Clinical Relevance

Result: KPV (α-MSH fragment) anti-inflammatory; gut/IBD applications; oral use. See PMID: 18092346

Limitations

Preclinical (murine); human clinical data limited.

Effect of Tesofensine on Bodyweight Loss, Body Composition, and Quality of Life in Obese Patients: A Randomised, Double-Blind, Placebo-Controlled Trial

Astrup A, et al. • The Lancet (2008)

RCT

Level A

Tesofensine

n = 203

PMID: 18950853

Key Findings

Tesofensine (0.5 mg daily) produced 9.2% weight loss at 24 weeks vs diet+placebo; 1.0 mg produced 10.6%
Dopamine/noradrenaline/serotonin reuptake inhibitor; approximately double weight loss vs approved drugs at time
Common AEs: dry mouth, nausea, constipation, insomnia; 0.5 mg increased heart rate ~7 bpm

Clinical Relevance

Result: Tesofensine RCT; significant bodyweight loss and body composition improvement. See PMID: 18950853

Limitations

Phase 2; phase 3 and long-term safety data required.

Noopept Stimulates the Expression of NGF and BDNF in Rat Hippocampus

Ostrovskaya RU, et al. • Bulletin of Experimental Biology and Medicine (2008)

Animal

Level B

Noopept

0PMID: 19240853

Key Findings

Noopept increased NGF and BDNF mRNA in rat hippocampus (acute and chronic)
Chronic treatment potentiated neurotrophic effects without tolerance
Cycloprolylglycine prodrug; proposed for mild cognitive impairment

Clinical Relevance

Result: Noopept increased NGF/BDNF in hippocampus; neuroprotective basis. See PMID: 19240853

Limitations

Preclinical; human RCTs limited.

Semax and BDNF Gene Expression in Hippocampus

Agapova TY, et al. • Doklady Biological Sciences (2007)

Animal

Level B

Semax

PMID: 17929710

Key Findings

Significant increase in BDNF mRNA expression
Effects seen in hippocampus within hours
Dose-dependent response observed
NGF expression also upregulated

Clinical Relevance

Result: BDNF mRNA upregulation in hippocampus; dose-dependent. Mechanistic basis for cognitive claims. See PMID: 17929710

Limitations

Animal study. Human neuroimaging studies would strengthen evidence.

Tesamorelin for HIV-Associated Lipodystrophy

Falutz J, et al. • JAMA (2007)

RCT

Level A

Tesamorelin

n = 412

PMID: 17635889

Key Findings

15% reduction in visceral adipose tissue at 26 weeks
Improved body image and quality of life
Beneficial lipid effects (reduced triglycerides)
FDA approval basis study

Clinical Relevance

FDA-approved GHRH analog. Result: 15% visceral fat reduction at 26 weeks. See PMID: 17635889

Sermorelin: A Review of Its Use in the Diagnosis and Treatment of Children with Idiopathic Growth Hormone Deficiency

McKeage K, Perry CM • Paediatric Drugs (2007)

Review

Level B

Sermorelin

PMID: 18031173

Key Findings

Sermorelin (GHRH 1-29) stimulates pituitary GH release; FDA-approved for pediatric GH deficiency (discontinued 2008 commercially)
Once-daily subcutaneous sermorelin effective for catch-up growth in GH-deficient children
Fewer false positives than other provocative tests when used diagnostically

Clinical Relevance

Result: sermorelin (GHRH 1-29) stimulates pituitary GH; FDA-approved pediatric (discontinued). See PMID: 18031173

Limitations

Review focused on pediatric use; adult data limited.

Progressive Reduction in Body Weight After Treatment with the Amylin Analog Pramlintide in Obese Subjects

Smith SR, et al. • Obesity (2007)

RCT

Level B

Pramlintide

n = 204

PMID: 17504894

Key Findings

Pramlintide dose-escalation produced progressive weight loss in obese subjects
Amylin analog; delays gastric emptying, reduces glucagon, suppresses appetite
FDA-approved for T1D and T2D with insulin; modest HbA1c and weight benefit

Clinical Relevance

Result: pramlintide weight loss in obese subjects; amylin analog for diabetes. See PMID: 17504894

Thymosin Alpha-1 in Chronic Hepatitis B: Meta-Analysis

You J, et al. • Journal of Viral Hepatitis (2006)

Meta-Analysis

Level A

Thymosin Alpha-1

n = 842

PMID: 16441128

Key Findings

Higher rates of sustained virological response
Synergistic with interferon therapy
Improved HBeAg seroconversion rates
Well-tolerated with minimal side effects

Clinical Relevance

Approved for HBV in multiple countries. Result: higher SVR, synergistic with interferon. See PMID: 16441128

Prolonged Stimulation of GH and IGF-1 Secretion by CJC-1295, a Long-Acting GHRH Analog, in Healthy Adults

Teichman SL, et al. • Journal of Clinical Endocrinology & Metabolism (2006)

RCT

Level B

CJC-1295

n = 54

PMID: 16753012

Key Findings

Single dose increased mean GH and IGF-1 for 6+ days
Sustained elevation without tachyphylaxis in 2-week repeat dosing
Well tolerated; supports weekly dosing in clinical use

Clinical Relevance

Result: single dose increased GH/IGF-1 for 6+ days; sustained with weekly dosing. See PMID: 16753012

Limitations

Small sample; long-term safety and efficacy beyond 2 weeks not fully established.

Semax in Acute Ischemic Stroke

Gusev EI, Skvortsova VI, et al. • Zhurnal Nevrologii i Psikhiatrii (2005)

RCT

Level B

Semax

n = 120

PMID: 15981583

Key Findings

Improved neurological outcomes at 21 days
Better functional recovery on Barthel Index
Reduced infarct volume on imaging
Good safety profile

Clinical Relevance

Result: improved neurological outcomes at 21 days; Russian regulatory approval. See PMID: 15981583

Limitations

Single-center study. Needs replication in Western populations.

Thymosin Beta-4 and Cardiac Repair

Bock-Marquette I, et al. • Nature (2004)

Animal

Level B

TB-500

PMID: 15269784

Key Findings

Promotes cardiac cell migration and survival
Activates ILK (integrin-linked kinase)
Reduced infarct size in MI models
Promotes angiogenesis

Clinical Relevance

Result: cardiac cell migration, reduced infarct size (animal). Rationale for tissue repair. See PMID: 15269784

Limitations

Animal study. Human cardiac trials in early stages.

Synthetic Tetrapeptide Epitalon Restores Telomere Elongation

Khavinson VH, et al. • Bulletin of Experimental Biology and Medicine (2003)

Clinical

Level B

Epitalon

PMID: 12374937

Key Findings

Activation of telomerase gene expression
Elongation of telomeres in human somatic cells
Significant increase in biological lifespan in models
Normalization of pineal gland function

Clinical Relevance

Result: telomerase activation, telomere elongation in somatic cells; pineal normalization. See PMID: 12374937

Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism in Obese Mice

Heffernan MA, et al. • Endocrinology (2001)

Animal

Level C

AOD-9604

0PMID: 11713213

Key Findings

AOD9604 reduced body weight gain and increased fat oxidation in obese mice
Did not induce hyperglycemia or reduce insulin secretion (unlike full-length hGH)
Mechanism distinct from GH receptor; does not stimulate cell proliferation

Clinical Relevance

Result: AOD9604 reduced weight gain, increased fat oxidation in obese mice; no hyperglycemia. See PMID: 11713213

Limitations

Preclinical (rodent); human clinical data limited.

Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GHRH Receptor

Ghigo E, et al. • Journal of Clinical Endocrinology and Metabolism (2001)

Clinical

Level B

GHRP-2

n = 8

PMID: 11443201

Key Findings

GHRP-2 stimulated GH in patients with GHRH receptor mutations (GHRH-independent pathway)
Stronger GH pulse than GHRP-6; less hunger stimulation in practice
Synthetic ghrelin analog; consistent GH secretagogue

Clinical Relevance

Result: GHRP-2 effective GH secretagogue; works in GHRH-deficient subjects. See PMID: 11443201

Limitations

Small sample; healthy-volunteer data limited.

Ipamorelin: A Novel GH Secretagogue

Raun K, Hansen BS, et al. • European Journal of Endocrinology (1998)

RCT

Level B

Ipamorelin

n = 24

PMID: 9491042

Key Findings

Dose-dependent GH release
No significant effect on ACTH or cortisol
No effect on prolactin
Minimal effect on appetite (vs GHRP-6)

Clinical Relevance

Result: dose-dependent GH release; no ACTH/cortisol or prolactin; minimal appetite effect. See PMID: 9491042

Oral Growth Hormone Secretagogue MK-677 Reverses the Decline in Pulsatile GH Release in Elderly Men

Chapman IM, et al. • Journal of Clinical Endocrinology & Metabolism (1996)

RCT

Level B

MK-677

n = 32

PMID: 8964844

Key Findings

MK-677 restored pulsatile GH release toward youthful pattern in elderly men
Increased IGF-1 and improved nitrogen balance
Oral bioavailability; once-daily dosing

Clinical Relevance

Result: oral MK-677 restored pulsatile GH in elderly; IGF-1 increase, nitrogen balance. See PMID: 8964844

Limitations

Older study; long-term safety and use in non-elderly populations require further data.

Evaluation of Melanotan-II, a Superpotent Cyclic Melanotropic Peptide in a Pilot Phase-I Clinical Study

Dorr RT, et al. • Life Sciences (1996)

Case Series

Level C

Melanotan II

n = 3

PMID: 8637402

Key Findings

MT-II produced tanning after 5 low doses every other day; increased pigmentation in face, upper body
Spontaneous erections reported (1-5 h); led to erectile dysfunction trials (PMID 9679884)
Mild nausea, somnolence, fatigue at higher doses; recommended dose 0.025 mg/kg/day

Clinical Relevance

Result: Melanotan II melanocortin agonist; tanning and libido/erectile effects. PT-141 FDA-approved derivative. See PMID: 8637402

Limitations

Small pilot; MT-II not FDA-approved; use off-label.

Growth Hormone-Releasing Activity of Hexarelin in Humans. A Dose-Response Study

Arvat E, et al. • Journal of Clinical Endocrinology and Metabolism (1996)

RCT

Level B

Hexarelin

n = 8

PMID: 7957536

Key Findings

Hexarelin potently releases GH after IV, SC, intranasal, and oral administration
Dose-dependent GH response; works via GHS-R1a
Also stimulates cortisol and prolactin at higher doses

Clinical Relevance

Result: hexarelin effective GH secretagogue; multiple routes of administration. See PMID: 7957536

Limitations

Small sample; older study.

Consistent GH Responses to Repeated Injection of GH-Releasing Hexapeptide (GHRP-6) and the Non-Peptide GH Secretagogue L-692,585

Chapman IM, et al. • Journal of Clinical Endocrinology and Metabolism (1996)

Clinical

Level B

GHRP-6

n = 8

PMID: 7636426

Key Findings

GHRP-6 produced consistent GH responses on repeated injection in healthy men
Dose-dependent GH release; activates pituitary signaling pathway
Foundation for later GHS development (e.g. ipamorelin, hexarelin)

Clinical Relevance

Result: GHRP-6 reliable GH secretagogue; consistent repeated dosing. See PMID: 7636426

Limitations

Small sample; healthy volunteers only.

Evidence Level Grading System

Strong Evidence: Multiple well-designed RCTs or meta-analyses with consistent results.

Moderate Evidence: Limited RCTs, well-designed cohort studies, or consistent results from observational studies.

Limited Evidence: Case series, case reports, or extrapolation from higher-quality studies.

Expert Opinion: Clinical experience, mechanistic rationale, or extrapolation without direct evidence.

Research Disclaimer

This database provides summaries of key research for educational purposes. It is not comprehensive and should not replace systematic literature review. Study interpretations reflect clinical relevance but individual patient factors must guide decisions. Always verify original sources before clinical application.

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Studies Indexed

Level A Studies

RCTs & Meta-Analyses

Key Studies

Showing 43 of 43 studies

Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM, et al. • New England Journal of Medicine (2023)

RCT

Level A

Retatrutide

n = 338

PMID: 37396564

Key Findings

Retatrutide (GLP-1/GIP/glucagon agonist) produced dose-dependent weight loss up to 24.2% at 48 weeks (12 mg)
Superior to placebo and comparable/superior to dual agonists; low hypoglycemia risk
Clinically meaningful glucose-lowering and cardiorenal risk reduction

Clinical Relevance

Result: retatrutide (GLP-1/GIP/glucagon) up to 24.2% weight loss at 48 weeks. See PMID: 37396564

Limitations

Phase 2; long-term and post-approval data still emerging.

The Mitochondrially Targeted Peptide Elamipretide (SS-31) Improves ADP Sensitivity in Aged Mitochondria by Increasing Uptake Through the Adenine Nucleotide Translocator

Siegel MP, et al. • Antioxidants & Redox Signaling (2023)

In Vitro

Level B

SS-31

PMID: 37462785

Key Findings

SS-31 binds cardiolipin, improves ANT function and ATP production; reduces mitochondrial ROS
MMPOWER-3 RCT in primary mitochondrial myopathy; heart failure and kidney disease trials ongoing
Well tolerated; supports use in mitochondrial and repair protocols

Clinical Relevance

Result: SS-31 (elamipretide) mitochondria-targeted; supports mitochondrial dysfunction. See PMID: 37462785

Limitations

Clinical approval path ongoing; much evidence from mechanistic and phase 2 trials.

Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)

Jastreboff AM, Aronne LJ, et al. • New England Journal of Medicine (2022)

RCT

Level A

Tirzepatide

n = 2,539

PMID: 35658024

Key Findings

15mg dose: 22.5% mean weight loss at 72 weeks
10mg dose: 21.4% weight loss
5mg dose: 16.0% weight loss
Superior to semaglutide in head-to-head comparisons

Clinical Relevance

Study result: dual GIP/GLP-1 mechanism; superior weight loss vs GLP-1 alone. See PMID: 35658024

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial

Comninos AN, et al. • JAMA Network Open (2022)

RCT

Level B

Kisspeptin

n = 32

PMID: 36287566

Key Findings

Kisspeptin-54 triggered egg maturation in IVF; intranasal kisspeptin rapidly stimulates gonadotropin release
RCT in hypoactive sexual desire disorder; kisspeptin modulates reproductive axis and libido
Pulsatile kisspeptin trialled in hypogonadotropic hypogonadism

Clinical Relevance

Result: Kisspeptin stimulates gonadotropin release; supports fertility and hypogonadism. See PMID: 36287566

Limitations

Larger phase 3 and long-term data still limited.

Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

Wilding JPH, Batterham RL, et al. • New England Journal of Medicine (2021)

RCT

Level A

Semaglutide

n = 1,961

PMID: 33567185

Key Findings

14.9% mean weight loss at 68 weeks vs 2.4% placebo
86.4% achieved ≥5% weight loss
69.1% achieved ≥10% weight loss
Significant improvements in cardiometabolic risk factors

Clinical Relevance

Result: semaglutide 2.4mg weekly highly effective for obesity. NNT ~2 for clinically meaningful weight loss. See PMID: 33567185

Limitations

GI side effects common. Long-term data beyond 68 weeks still emerging.

Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells

Khavinson VKh, Linkova NS, et al. • Biology Bulletin Reviews (2021)

Clinical

Level B

Thymalin

PMID: 33237528

Key Findings

Thymalin (polypeptide complex from calf thymus) regulates immune function and hematopoiesis
Long-term trial in 266 elderly: reduced acute respiratory disease incidence 2.0–2.4× and mortality 2.0–2.1× vs control
Regulates gene expression, cytokine production, and cell differentiation; minimal side effects

Clinical Relevance

Result: Thymalin reduced respiratory disease incidence and mortality 2× in elderly. See PMID: 33237528

Limitations

Much data from Russian literature; more Western RCTs would strengthen evidence.

Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model

Sochacki KA, et al. • Antimicrobial Agents and Chemotherapy (2021)

Animal

Level B

LL-37

0PMID: 34680791

Key Findings

Human cathelicidin LL-37 reduced MRSA burden and improved wound healing in surgical wound model
LL-37 effective against polymicrobial infected wounds; broad-spectrum antimicrobial
Only human cathelicidin; expressed by neutrophils and epithelial cells; innate immunity

Clinical Relevance

Result: LL-37 antimicrobial peptide; membrane disruption; wound-healing and gut applications. See PMID: 34680791

Limitations

Key evidence in animal models; topical/systemic human trials limited.

AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in APP/PS1 Mouse via PI3K/AKT

Sun Y, et al. • Brain Sciences (2021)

Animal

Level B

Dihexa

0PMID: 34827486

Key Findings

Dihexa rescued cognitive impairment and memory in APP/PS1 Alzheimer model
PI3K/AKT pathway; hepatocyte growth factor/c-Met activation; synaptogenic
Orally bioavailable; crosses BBB; angiotensin IV analog

Clinical Relevance

Result: Dihexa improved cognition and memory in AD model; procognitive/synaptogenic. See PMID: 34827486

Limitations

Preclinical; human trials limited.

BPC 157 and Tendon Healing: Systematic Review

Gwyer D, Wragg NM, Wilson SL • Journal of Orthopaedic Surgery and Research (2019)

Review

Level B

BPC-157

PMID: 31399107

Key Findings

Consistent promotion of tendon healing in animal models
Enhanced collagen organization
Increased VEGF expression and angiogenesis
Anti-inflammatory effects documented

Clinical Relevance

Preclinical: tendon healing, collagen organization, VEGF. Human RCTs limited. See PMID: 31399107

Limitations

Most evidence from animal studies. Human clinical trials limited.

Bremelanotide for Hypoactive Sexual Desire Disorder in Women (RECONNECT)

Kingsberg SA, et al. • Obstetrics & Gynecology (2019)

RCT

Level A

PT-141

n = 1,247

PMID: 31135757

Key Findings

Significant increase in satisfying sexual events
Improved sexual desire scores
Reduced distress related to low desire
Effects seen as early as first dose

Clinical Relevance

FDA-approved for premenopausal HSDD. Result: increased satisfying sexual events. See PMID: 31135757

BPC 157 and Gastrointestinal Protective Effects

Sikiric P, et al. • Current Pharmaceutical Design (2018)

Review

Level B

BPC-157

PMID: 29589535

Key Findings

Protection against NSAID-induced GI damage
Accelerated healing of gastric ulcers
Beneficial effects on inflammatory bowel conditions
Oral bioavailability demonstrated

Clinical Relevance

Result: oral BPC-157 GI protection, gastric ulcer healing; oral bioavailability shown. See PMID: 29589535

Limitations

Human dose-finding studies needed. Optimal oral dosing unclear.

Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

Yen K, et al. • Scientific Reports (2018)

Cohort

Level B

Humanin

0PMID: 30242290

Key Findings

Humanin administration improved cognition in aged mice
SNP in humanin-coding region associated with accelerated cognitive aging in older adults
Circulating humanin decreases with age; mitochondrial-derived peptide

Clinical Relevance

Result: Humanin neuroprotective; associated with cognitive aging in humans. See PMID: 30242290

Limitations

Observational human data; causal trials limited.

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

Holman RR, et al. • New England Journal of Medicine (2017)

RCT

Level A

Exenatide

n = 14,752

PMID: 29182939

Key Findings

EXSCEL: exenatide once-weekly noninferior to placebo for CV death, MI, stroke (HR 0.91)
14% lower all-cause mortality with exenatide vs placebo (6.9% vs 7.9%)
Median follow-up 3.2 years; 73% had prior CVD; established CV safety

Clinical Relevance

Result: exenatide once-weekly CV safe in T2D; noninferiority for MACE; potential mortality benefit. See PMID: 29182939

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Baar MP, et al. • Cell (2017)

Animal

Level B

FOXO4-DRI

0PMID: 28340342

Key Findings

FOXO4-DRI interferes with FOXO4-p53 interaction; induces apoptosis in senescent cells
Restored fitness, fur density, and kidney function in aged and doxorubicin-treated mice
Proof-of-concept for senolytic peptide; human trials limited

Clinical Relevance

Result: FOXO4-DRI targeted senolysis; improved healthspan in preclinical models. See PMID: 28340342

Limitations

Preclinical; human safety and efficacy data limited.

Cerebrolysin in Patients with Mild to Moderate Dementia: Meta-Analysis

Gauthier S, Proaño JV, et al. • Dementia and Geriatric Cognitive Disorders (2015)

Meta-Analysis

Level A

Cerebrolysin

n = 1,245

PMID: 26227422

Key Findings

Significant improvement in global clinical function (CGI)
Cognitive benefits measured by ADAS-cog
Effects maintained at 6-month follow-up
Good safety profile in elderly patients

Clinical Relevance

Level A evidence: Cerebrolysin for mild-moderate dementia. Benefit in subjects non-responsive to cholinesterase inhibitors. See PMID: 26227422

GHK Peptide as a Natural Modulator of Gene Expression in Regenerative Medicine

Pickart L, Vasquez-Soltero JM, Margolina A • BioMed Research International (2015)

Review

Level B

GHK-Cu

PMID: 6481226

Key Findings

GHK-Cu naturally declines with age
Activates 31.2% of human genes (>50% change)
Stimulates collagen, elastin, and glycosaminoglycans
Promotes nerve and blood vessel growth

Clinical Relevance

Result: GHK-Cu activates 31.2% of human genes; collagen, elastin, nerve/vessel growth. See PMID: 6481226

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

Lee C, et al. • Cell Metabolism (2015)

Animal

Level B

MOTS-c

0PMID: 26071498

Key Findings

MOTS-c (16-aa, mitochondrial 12S rRNA) targets skeletal muscle via folate-AMPK pathway
Prevented age-dependent and diet-induced insulin resistance and obesity in mice
Circulating MOTS-c decreases with aging; lower in T2D; potential senotherapeutic role

Clinical Relevance

Result: MOTS-c prevented insulin resistance and obesity in mice; folate-AMPK pathway. See PMID: 26071498

Limitations

Key evidence in rodents; human RCTs still limited.

ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes

Brines M, et al. • Molecular Medicine (2015)

RCT

Level B

ARA-290

n = 74

PMID: 25387363

Key Findings

ARA-290 (innate repair receptor agonist) improved neuropathic symptoms and metabolic control in T2D
Improved corneal nerve fiber density and PainDetect scores; no hematopoietic effects
Phase 2 sarcoidosis neuropathy trials showed significant pain relief and QoL improvement

Clinical Relevance

Result: ARA-290 improved metabolic control and neuropathic symptoms in T2D subjects. See PMID: 25387363

Limitations

Larger phase 3 and long-term data still limited.

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Pi-Sunyer X, et al. • New England Journal of Medicine (2015)

RCT

Level A

Liraglutide

n = 3,731

PMID: 26132939

Key Findings

3.0 mg liraglutide daily: 8.4 kg mean weight loss at 56 weeks vs 2.8 kg placebo
63.2% achieved ≥5% weight loss vs 27.1% placebo; 33.1% achieved ≥10% vs 10.6%
Improvements in cardiometabolic risk factors; nausea and constipation most common AEs

Clinical Relevance

Result: liraglutide 3 mg daily effective for weight management in obesity; FDA-approved (Saxenda). See PMID: 26132939

Cerebrolysin in Acute Ischemic Stroke: CASTA Trial

Heiss WD, Brainin M, et al. • Stroke (2012)

RCT

Level B

Cerebrolysin

n = 1,070

PMID: 22343647

Key Findings

Improved motor function at 90 days in moderate strokes
Significant benefit in NIHSS 8-15 subgroup
Earlier treatment associated with better outcomes
Safe with standard stroke care

Clinical Relevance

Result: adjunctive therapy in moderate acute ischemic stroke; benefit when started early. See PMID: 22343647

Limitations

Primary endpoint not met in ITT analysis. Benefits seen in pre-specified subgroups.

Effect of Teriparatide on Bone Mineral Density and Fracture in Postmenopausal Osteoporosis: Meta-Analysis of RCTs

Nieves JW, et al. • Osteoporosis International (2012)

Meta-Analysis

Level A

Teriparatide

n = 2,388

PMID: 22257045

Key Findings

Eight RCTs: teriparatide increased spine and hip BMD vs placebo/controls
Reduced vertebral and nonvertebral fracture risk in postmenopausal osteoporosis
FDA-approved PTH(1-34) anabolic; intermittent dosing builds bone

Clinical Relevance

Result: teriparatide meta-analysis; improved BMD and fracture risk in osteoporosis. See PMID: 22257045

Afamelanotide, an Agonistic Analog of α-MSH, in Dermal Phototoxicity of Erythropoietic Protoporphyria

Harms J, et al. • Expert Opinion on Investigational Drugs (2010)

Case Series

Level C

Melanotan 1

n = 5

PMID: 21073357

Key Findings

Afamelanotide (MT-1) increased light tolerance and melanin in EPP patients
α-MSH analog; induces epidermal melanin; FDA-approved implant for EPP (Scenesse)
Tanning and photoprotection; different from MT-II (libido/tanning)

Clinical Relevance

Result: Melanotan 1 (afamelanotide) photoprotection in EPP; FDA-approved for EPP. See PMID: 21073357

Limitations

Small series; EPP is rare; off-label tanning use not approved.

A Randomized Controlled Trial of Intranasal Oxytocin as an Adjunct to Exposure Therapy for Social Anxiety Disorder

Guastella AJ, et al. • Psychoneuroendocrinology (2009)

RCT

Level B

Oxytocin

n = 25

PMID: 19246160

Key Findings

Intranasal oxytocin combined with exposure therapy reduced social threat perception
Improved encoding of positive social cues and communication processes
Small sample; oxytocin effects context-dependent in anxiety populations

Clinical Relevance

Result: intranasal oxytocin as adjunct to exposure therapy may support social anxiety treatment. See PMID: 19246160

Limitations

Small RCT; replication and larger trials needed.

Selank in Generalized Anxiety: Clinical Trial

Zozulia AA, et al. • Bulletin of Experimental Biology and Medicine (2008)

RCT

Level B

Selank

n = 62

PMID: 19504360

Key Findings

Significant reduction in anxiety scores
Comparable efficacy to phenazepam (benzodiazepine)
No sedation or cognitive impairment
No dependence or withdrawal observed

Clinical Relevance

Result: anxiety reduction comparable to phenazepam; no sedation or dependence. See PMID: 19504360

Melanocortin-Derived Tripeptide KPV Has Anti-Inflammatory Potential in Murine Models of Inflammatory Bowel Disease

Kokot A, et al. • Inflammatory Bowel Diseases (2008)

Animal

Level C

KPV

0PMID: 18092346

Key Findings

KPV (α-MSH 11-13) reduced inflammatory infiltrates and MPO in DSS-induced colitis; earlier recovery and weight regain
Anti-inflammatory effect distinct from classic melanocortin receptors; inhibits IL-1β
Rescued MC1R-deficient mice from lethal DSS colitis

Clinical Relevance

Result: KPV (α-MSH fragment) anti-inflammatory; gut/IBD applications; oral use. See PMID: 18092346

Limitations

Preclinical (murine); human clinical data limited.

Effect of Tesofensine on Bodyweight Loss, Body Composition, and Quality of Life in Obese Patients: A Randomised, Double-Blind, Placebo-Controlled Trial

Astrup A, et al. • The Lancet (2008)

RCT

Level A

Tesofensine

n = 203

PMID: 18950853

Key Findings

Tesofensine (0.5 mg daily) produced 9.2% weight loss at 24 weeks vs diet+placebo; 1.0 mg produced 10.6%
Dopamine/noradrenaline/serotonin reuptake inhibitor; approximately double weight loss vs approved drugs at time
Common AEs: dry mouth, nausea, constipation, insomnia; 0.5 mg increased heart rate ~7 bpm

Clinical Relevance

Result: Tesofensine RCT; significant bodyweight loss and body composition improvement. See PMID: 18950853

Limitations

Phase 2; phase 3 and long-term safety data required.

Noopept Stimulates the Expression of NGF and BDNF in Rat Hippocampus

Ostrovskaya RU, et al. • Bulletin of Experimental Biology and Medicine (2008)

Animal

Level B

Noopept

0PMID: 19240853

Key Findings

Noopept increased NGF and BDNF mRNA in rat hippocampus (acute and chronic)
Chronic treatment potentiated neurotrophic effects without tolerance
Cycloprolylglycine prodrug; proposed for mild cognitive impairment

Clinical Relevance

Result: Noopept increased NGF/BDNF in hippocampus; neuroprotective basis. See PMID: 19240853

Limitations

Preclinical; human RCTs limited.

Semax and BDNF Gene Expression in Hippocampus

Agapova TY, et al. • Doklady Biological Sciences (2007)

Animal

Level B

Semax

PMID: 17929710

Key Findings

Significant increase in BDNF mRNA expression
Effects seen in hippocampus within hours
Dose-dependent response observed
NGF expression also upregulated

Clinical Relevance

Result: BDNF mRNA upregulation in hippocampus; dose-dependent. Mechanistic basis for cognitive claims. See PMID: 17929710

Limitations

Animal study. Human neuroimaging studies would strengthen evidence.

Tesamorelin for HIV-Associated Lipodystrophy

Falutz J, et al. • JAMA (2007)

RCT

Level A

Tesamorelin

n = 412

PMID: 17635889

Key Findings

15% reduction in visceral adipose tissue at 26 weeks
Improved body image and quality of life
Beneficial lipid effects (reduced triglycerides)
FDA approval basis study

Clinical Relevance

FDA-approved GHRH analog. Result: 15% visceral fat reduction at 26 weeks. See PMID: 17635889

Sermorelin: A Review of Its Use in the Diagnosis and Treatment of Children with Idiopathic Growth Hormone Deficiency

McKeage K, Perry CM • Paediatric Drugs (2007)

Review

Level B

Sermorelin

PMID: 18031173

Key Findings

Sermorelin (GHRH 1-29) stimulates pituitary GH release; FDA-approved for pediatric GH deficiency (discontinued 2008 commercially)
Once-daily subcutaneous sermorelin effective for catch-up growth in GH-deficient children
Fewer false positives than other provocative tests when used diagnostically

Clinical Relevance

Result: sermorelin (GHRH 1-29) stimulates pituitary GH; FDA-approved pediatric (discontinued). See PMID: 18031173

Limitations

Review focused on pediatric use; adult data limited.

Progressive Reduction in Body Weight After Treatment with the Amylin Analog Pramlintide in Obese Subjects

Smith SR, et al. • Obesity (2007)

RCT

Level B

Pramlintide

n = 204

PMID: 17504894

Key Findings

Pramlintide dose-escalation produced progressive weight loss in obese subjects
Amylin analog; delays gastric emptying, reduces glucagon, suppresses appetite
FDA-approved for T1D and T2D with insulin; modest HbA1c and weight benefit

Clinical Relevance

Result: pramlintide weight loss in obese subjects; amylin analog for diabetes. See PMID: 17504894

Thymosin Alpha-1 in Chronic Hepatitis B: Meta-Analysis

You J, et al. • Journal of Viral Hepatitis (2006)

Meta-Analysis

Level A

Thymosin Alpha-1

n = 842

PMID: 16441128

Key Findings

Higher rates of sustained virological response
Synergistic with interferon therapy
Improved HBeAg seroconversion rates
Well-tolerated with minimal side effects

Clinical Relevance

Approved for HBV in multiple countries. Result: higher SVR, synergistic with interferon. See PMID: 16441128

Prolonged Stimulation of GH and IGF-1 Secretion by CJC-1295, a Long-Acting GHRH Analog, in Healthy Adults

Teichman SL, et al. • Journal of Clinical Endocrinology & Metabolism (2006)

RCT

Level B

CJC-1295

n = 54

PMID: 16753012

Key Findings

Single dose increased mean GH and IGF-1 for 6+ days
Sustained elevation without tachyphylaxis in 2-week repeat dosing
Well tolerated; supports weekly dosing in clinical use

Clinical Relevance

Result: single dose increased GH/IGF-1 for 6+ days; sustained with weekly dosing. See PMID: 16753012

Limitations

Small sample; long-term safety and efficacy beyond 2 weeks not fully established.

Semax in Acute Ischemic Stroke

Gusev EI, Skvortsova VI, et al. • Zhurnal Nevrologii i Psikhiatrii (2005)

RCT

Level B

Semax

n = 120

PMID: 15981583

Key Findings

Improved neurological outcomes at 21 days
Better functional recovery on Barthel Index
Reduced infarct volume on imaging
Good safety profile

Clinical Relevance

Result: improved neurological outcomes at 21 days; Russian regulatory approval. See PMID: 15981583

Limitations

Single-center study. Needs replication in Western populations.

Thymosin Beta-4 and Cardiac Repair

Bock-Marquette I, et al. • Nature (2004)

Animal

Level B

TB-500

PMID: 15269784

Key Findings

Promotes cardiac cell migration and survival
Activates ILK (integrin-linked kinase)
Reduced infarct size in MI models
Promotes angiogenesis

Clinical Relevance

Result: cardiac cell migration, reduced infarct size (animal). Rationale for tissue repair. See PMID: 15269784

Limitations

Animal study. Human cardiac trials in early stages.

Synthetic Tetrapeptide Epitalon Restores Telomere Elongation

Khavinson VH, et al. • Bulletin of Experimental Biology and Medicine (2003)

Clinical

Level B

Epitalon

PMID: 12374937

Key Findings

Activation of telomerase gene expression
Elongation of telomeres in human somatic cells
Significant increase in biological lifespan in models
Normalization of pineal gland function

Clinical Relevance

Result: telomerase activation, telomere elongation in somatic cells; pineal normalization. See PMID: 12374937

Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism in Obese Mice

Heffernan MA, et al. • Endocrinology (2001)

Animal

Level C

AOD-9604

0PMID: 11713213

Key Findings

AOD9604 reduced body weight gain and increased fat oxidation in obese mice
Did not induce hyperglycemia or reduce insulin secretion (unlike full-length hGH)
Mechanism distinct from GH receptor; does not stimulate cell proliferation

Clinical Relevance

Result: AOD9604 reduced weight gain, increased fat oxidation in obese mice; no hyperglycemia. See PMID: 11713213

Limitations

Preclinical (rodent); human clinical data limited.

Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GHRH Receptor

Ghigo E, et al. • Journal of Clinical Endocrinology and Metabolism (2001)

Clinical

Level B

GHRP-2

n = 8

PMID: 11443201

Key Findings

GHRP-2 stimulated GH in patients with GHRH receptor mutations (GHRH-independent pathway)
Stronger GH pulse than GHRP-6; less hunger stimulation in practice
Synthetic ghrelin analog; consistent GH secretagogue

Clinical Relevance

Result: GHRP-2 effective GH secretagogue; works in GHRH-deficient subjects. See PMID: 11443201

Limitations

Small sample; healthy-volunteer data limited.

Ipamorelin: A Novel GH Secretagogue

Raun K, Hansen BS, et al. • European Journal of Endocrinology (1998)

RCT

Level B

Ipamorelin

n = 24

PMID: 9491042

Key Findings

Dose-dependent GH release
No significant effect on ACTH or cortisol
No effect on prolactin
Minimal effect on appetite (vs GHRP-6)

Clinical Relevance

Result: dose-dependent GH release; no ACTH/cortisol or prolactin; minimal appetite effect. See PMID: 9491042

Oral Growth Hormone Secretagogue MK-677 Reverses the Decline in Pulsatile GH Release in Elderly Men

Chapman IM, et al. • Journal of Clinical Endocrinology & Metabolism (1996)

RCT

Level B

MK-677

n = 32

PMID: 8964844

Key Findings

MK-677 restored pulsatile GH release toward youthful pattern in elderly men
Increased IGF-1 and improved nitrogen balance
Oral bioavailability; once-daily dosing

Clinical Relevance

Result: oral MK-677 restored pulsatile GH in elderly; IGF-1 increase, nitrogen balance. See PMID: 8964844

Limitations

Older study; long-term safety and use in non-elderly populations require further data.

Evaluation of Melanotan-II, a Superpotent Cyclic Melanotropic Peptide in a Pilot Phase-I Clinical Study

Dorr RT, et al. • Life Sciences (1996)

Case Series

Level C

Melanotan II

n = 3

PMID: 8637402

Key Findings

MT-II produced tanning after 5 low doses every other day; increased pigmentation in face, upper body
Spontaneous erections reported (1-5 h); led to erectile dysfunction trials (PMID 9679884)
Mild nausea, somnolence, fatigue at higher doses; recommended dose 0.025 mg/kg/day

Clinical Relevance

Result: Melanotan II melanocortin agonist; tanning and libido/erectile effects. PT-141 FDA-approved derivative. See PMID: 8637402

Limitations

Small pilot; MT-II not FDA-approved; use off-label.

Growth Hormone-Releasing Activity of Hexarelin in Humans. A Dose-Response Study

Arvat E, et al. • Journal of Clinical Endocrinology and Metabolism (1996)

RCT

Level B

Hexarelin

n = 8

PMID: 7957536

Key Findings

Hexarelin potently releases GH after IV, SC, intranasal, and oral administration
Dose-dependent GH response; works via GHS-R1a
Also stimulates cortisol and prolactin at higher doses

Clinical Relevance

Result: hexarelin effective GH secretagogue; multiple routes of administration. See PMID: 7957536

Limitations

Small sample; older study.

Consistent GH Responses to Repeated Injection of GH-Releasing Hexapeptide (GHRP-6) and the Non-Peptide GH Secretagogue L-692,585

Chapman IM, et al. • Journal of Clinical Endocrinology and Metabolism (1996)

Clinical

Level B

GHRP-6

n = 8

PMID: 7636426

Key Findings

GHRP-6 produced consistent GH responses on repeated injection in healthy men
Dose-dependent GH release; activates pituitary signaling pathway
Foundation for later GHS development (e.g. ipamorelin, hexarelin)

Clinical Relevance

Result: GHRP-6 reliable GH secretagogue; consistent repeated dosing. See PMID: 7636426

Limitations

Small sample; healthy volunteers only.

Evidence Level Grading System

Strong Evidence: Multiple well-designed RCTs or meta-analyses with consistent results.

Moderate Evidence: Limited RCTs, well-designed cohort studies, or consistent results from observational studies.

Limited Evidence: Case series, case reports, or extrapolation from higher-quality studies.

Expert Opinion: Clinical experience, mechanistic rationale, or extrapolation without direct evidence.

Research Disclaimer

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Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Key Findings

Clinical Relevance

Limitations

The Mitochondrially Targeted Peptide Elamipretide (SS-31) Improves ADP Sensitivity in Aged Mitochondria by Increasing Uptake Through the Adenine Nucleotide Translocator

Key Findings

Clinical Relevance

Limitations

Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)

Key Findings

Clinical Relevance

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial

Key Findings

Clinical Relevance

Limitations

Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

Key Findings

Clinical Relevance

Limitations

Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells

Key Findings

Clinical Relevance

Limitations

Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model

Key Findings

Clinical Relevance

Limitations

AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in APP/PS1 Mouse via PI3K/AKT

Key Findings

Clinical Relevance

Limitations

BPC 157 and Tendon Healing: Systematic Review

Key Findings

Clinical Relevance

Limitations

Bremelanotide for Hypoactive Sexual Desire Disorder in Women (RECONNECT)

Key Findings

Clinical Relevance

BPC 157 and Gastrointestinal Protective Effects

Key Findings

Clinical Relevance

Limitations

Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

Key Findings

Clinical Relevance

Limitations

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

Key Findings

Clinical Relevance

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Key Findings

Clinical Relevance

Limitations

Cerebrolysin in Patients with Mild to Moderate Dementia: Meta-Analysis

Key Findings

Clinical Relevance

GHK Peptide as a Natural Modulator of Gene Expression in Regenerative Medicine

Key Findings

Clinical Relevance

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

Key Findings

Clinical Relevance

Limitations

ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes

Key Findings

Clinical Relevance

Limitations

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Key Findings

Clinical Relevance

Cerebrolysin in Acute Ischemic Stroke: CASTA Trial

Key Findings

Clinical Relevance

Limitations

Effect of Teriparatide on Bone Mineral Density and Fracture in Postmenopausal Osteoporosis: Meta-Analysis of RCTs

Key Findings

Clinical Relevance

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