Dimitar Marinov, Ph.D.
Dimitar Marinov, Ph.D.Interested in learning about the most actively studied research peptides among the scientific community?
The experts at Peptides.org have it covered.
This comprehensive review will outline the most notable and effective research peptides, categorized by their potential research applications:
- Weight loss
- Increased lean muscle mass
- Skin improvement
- Healing and injury recovery
- Longevity and anti-aging
- Reproductive health
- Cognitive improvement
- Sleep enhancement
Keep reading to discover the most notable compounds that can provide these benefits according to research, and also discover the most reputable vendors of high-quality research peptides.
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Disclaimer: Peptides.org contains information about products that are intended for laboratory and research use only, unless otherwise explicitly stated. This information, including any referenced scientific or clinical research, is made available for educational purposes only. Likewise, any published information relative to the dosing and administration of reference materials is made available strictly for reference and shall not be construed to encourage the self-administration or any human use of said reference materials. Peptides.org makes every effort to ensure that any information it shares complies with national and international standards for clinical trial information and is committed to the timely disclosure of the design and results of all interventional clinical studies for innovative treatments publicly available or that may be made available. However, research is not considered conclusive. Peptides.org makes no claims that any products referenced can cure, treat or prevent any conditions, including any conditions referenced on its website or in print materials.
What are Peptides?
Peptides are molecules composed of amino acids linked by peptide bonds — similar to proteins but considerably shorter. By convention, a chain of no more than 50 amino acids is termed a peptide, but essentially a peptide is a small protein.
Their functions depend on the specific sequence of their amino acids, which allows them to target specific receptors and regulate biological processes [1].
Due to the variety of potential sequences and their diverse properties, peptides are versatile molecules that are central to numerous essential biological functions including, but not limited to:
- Cellular communication and motility
- Neurotransmission
- Endocrine signaling
- Metabolic process management
- Growth stimulation
- Recovery promotion
The pharmaceutical realm has leveraged the potential of peptides by either modifying naturally occurring ones or synthesizing new sequences, leading to therapeutic peptides with better pharmacokinetics, enhanced specificity, or fewer side effects [2].
Advancements in the field have spurred a notable growth in the development and approval of peptide-based therapeutic drugs, with over 60 currently approved for human use and hundreds more under investigation for their potential benefits [1, 2].
List of Peptides and What They Do
Below, we outline the most notable research peptides and categorize them according to their main benefits, as shown by clinical data.
These potential research applications include weight loss, improved body composition and muscle growth, tissue healing and recovery, and more.
Let's dig in:
Weight Loss Peptides
Peptide analogs of incretin hormones like glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have proven to be highly effective tools for weight loss.
Incretin mimetic peptides regulate blood sugar levels and appetite, ultimately aiding weight loss via improved satiety and reduced cravings [3, 4, 5].
Here are three of the most notable weight loss peptides:
Semaglutide
Semaglutide, developed by Novo Nordisk in 2012, is a synthetic agonist of the GLP-1 receptor. Its molecular structure consists of 31 amino acids, sharing a 94% similarity with the endogenous GLP-1 molecule [6, 7].
A distinct modification in semaglutide is the incorporation of an octadecanoic (C-18) diacid component, which extends its half-life to seven days, thereby enabling a once-weekly dosing regimen. It is approved by the United States Food and Drug Administration (FDA) for a range of indications, including type 2 diabetes (T2D) and weight reduction in both diabetics and nondiabetics [8, 9].
The FDA’s approval for semaglutide's use in weight management was based on the ongoing STEP clinical development program. This program encompasses several phase-3 trials (e.g., STEP 1-10, STEP TEENS, STEP UP) and mainly includes study volunteers with a body mass index (BMI) of at least 30 or at least 27 coupled with related health conditions such as type 2 diabetes (T2D).
Data from these trials have revealed that weekly administration of 2.4mg semaglutide led to a weight reduction ranging from 9.6% to 17.4% of the volunteers’ initial weight over a span of 68 weeks [10, 11].
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Liraglutide
Liraglutide is a GLP-1 receptor agonist consisting of 31 amino acids, with a 97% structural similarity to the native hormone [12]. It was developed by Novo Nordisk in the 1990s and is currently approved for a wide range of indications, such as T2D [13].
The peptide is marketed under the brand name Saxenda (up to 3mg/daily) for chronic weight management in non-diabetic adults, as evidenced by the outcomes of the SCALE clinical development program.
The SCALE Obesity and Prediabetes trial, the largest among the SCALE studies, examined 3,731 participants with a BMI of 30 or greater (or 27 or greater in conjunction with conditions like dyslipidemia or hypertension).
Over 56 weeks, the liraglutide recipients lost an average of 18.5 pounds (approximately 8% from baseline), whereas the placebo group shed an average of 6.2 pounds (around 2.6% from baseline) [14].
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Tirzepatide
Tirzepatide, a peptide composed of 39 amino acids, is a novel dual agonist of the both GIP and GLP-1 receptors, with a bias towards GIP [15].
Its molecular architecture fuses elements from the GIP hormone and a GLP-1 receptor agonist known as exenatide, alongside a C20 fatty di-acid moiety to extend its half-life to up to five days for once-weekly subcutaneous administration [16, 17].
The FDA approved tirzepatide for type 2 diabetes (T2D) treatment, now available under the brand name Mounjaro, following positive outcomes from the phase-3 trials of the SURPASS program, which showcased a reduction of up to -3.02% in glycated hemoglobin levels [18].
Currently, tirzepatide is under phase-3 evaluation in the SURMOUNT program to ascertain its efficacy for weight management in non-diabetic adults. The most recent trial within this program, SURMOUNT-3, revealed a 20.8% greater weight reduction than placebo following 72 weeks of tirzepatide therapy at doses of 10-15/mg weekly [19, 20].
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Body Composition Peptides
Peptides for improving body composition and increasing muscle mass work via a variety of mechanisms to upregulate muscle protein synthesis (MPS) while reducing muscle protein breakdown (MPB).
Perhaps the common mechanism is the upregulation of growth hormone (GH) and its main anabolic mediator, insulin-like growth factor-1 (IGF-1) [21].
Here are three of the most notable peptides for increasing lean muscle mass:
Sermorelin
Sermorelin, also known as GRF 1-29, is a synthetic analog of growth hormone-releasing hormone (GHRH), engineered by the biopharmaceutical company EMD Serono to stimulate GH production [22].
Sermorelin includes only the initial 29 amino acids of GHRH's 44 amino acid sequence, thereby making it the shortest functional GHRH analog [23].
Initially, the peptide received FDA approval for both diagnostic and therapeutic applications in addressing growth hormone deficiency. However, this approval was withdrawn for commercial considerations unrelated to its safety or efficacy [24].
Nevertheless, the available research underscores sermorelin's potential for muscle growth, with studies reporting a +2.78lb increase in lean body weight in participants following a 16-week regimen of 10mcg/kg/daily of sermorelin [25].
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CJC-1295 DAC
CJC-1295 DAC, a tetrasubstituted derivative of the peptide sermorelin, was developed by the Canadian biotechnology company ConjuChem. The primary objective of CJC-1295 DAC was to manage lipodystrophy in HIV/AIDS patients.
CJC-1295’s half-life is amplified through the incorporation of a Drug Affinity Complex (DAC), enabling binding to plasma proteins and thereby prolonging its half-life to eight days [26, 27, 28].
This peptide can significantly increase GH and IGF-1 levels, which is expected to exert notable anabolic effects on muscle tissue [29]. Yet, studies investigating its muscle-building potential are currently lacking.
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Ipamorelin
Ipamorelin is a pentapeptide that mimics the function of the hunger hormone ghrelin and activates its receptors throughout the body. In the pituitary gland, these receptors are called the growth hormone secretagogue receptors (GHS-Rs) and result in the release of GH [30].
The peptide was developed by Novo Nordisk and Helsinn Therapeutics and designed to emulate the effects of ghrelin within the gastrointestinal tract, thus aiding in peristalsis, a type of intestinal motility [31, 32].
Ipamorelin is under investigation for its potential to preserve muscle while increasing lean mass. Clinical studies show that ipamorelin can also significantly boost the release of GH without affecting other pituitary hormones [33].
Further preliminary studies suggest that ipamorelin increases appetite and promotes weight gain while providing protection against muscle atrophy in test animals, especially when exposed to catabolic agents [34, 35]. Unfortunately, clinical research regarding the muscle-building potential of ipamorelin is lacking.
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Skincare Peptides
Skincare peptides can help improve skin complexion and appearance via a wide range of mechanisms, such as by improving collagen production and preventing contraction in subcutaneous muscles.
Here are two of the most notable skincare peptides:
GHK-Cu
GHK-Cu (glycyl-l-histidyl-l-lysine-copper), also known as copper tripeptide, is an endogenous peptide that readily binds to copper ions (2+). It occurs naturally in all bodily fluids [36].
GHK-Cu has a sequence present in the structure of type I collagen, and it is thought to be one of the fragments released upon enzymatic collagen breakdown due to injury. Thus, the peptide is thought to act as a repair signal.
It has also been noted for its ability to modulate levels of MMP-1 and MMP-2, which are enzymes involved in the breakdown of old collagen and glycosaminoglycans [37].
Thus, GHK-Cu may promote turnover within the intracellular matrix, facilitating the replacement of old matrix components with newly synthesized ones [36].
These actions contribute to a multitude of skin benefits, including enhanced skin healing, skin tightening, reduction of wrinkles, smoothing of rough skin, and protection against photoaging. In particular, studies have documented a reduction of 55.8% in wrinkle volume and a 32.8% decrease in wrinkle depth over 8 weeks with daily application [38].
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Argireline
Argireline, scientifically known as Acetyl Hexapeptide-3 or Acetyl Hexapeptide-8, is a synthetic peptide made of six amino acids. It is commonly used in skincare products for its potential anti-wrinkle benefits.
Argireline is designed to reduce the appearance of fine lines and wrinkles by inhibiting the muscle movement of subcutaneous muscles, mimicking the effects of Botox. When applied topically, Argireline passes through the skin and acts as a competitive inhibitor of a protein called SNAP-25 (synaptosome-associated protein 25kDa). As a result, it blocks the release of acetylcholine at the neuromuscular synapses [39].
Through this action, the muscles relax, and wrinkles become less visible [40]. Studies suggest that a 10% Argireline cream can cause up to 50% wrinkle depth reduction when applied twice daily for one month [41].
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Healing Peptides
Peptides for healing and injury recovery have risen to the forefront of the research community, with the following two compounds receiving the most attention.
BPC-157
BPC-157, also known as Body Protection Compound-157, PL 14736, PL-10, or Bepecin, is a synthetically engineered pentadecapeptide initially developed in the 1990s [42].
The peptide is posited to stimulate the activity of growth factors and cells pertinent to connective tissue repair, such as fibroblasts. Additionally, it is suggested to enhance the production of vasodilators, notably nitric oxide (NO), potentially facilitating the healing of skin, tendons, and muscles [43, 44, 45, 46].
Most of the existing data on BPC-157 stem from preclinical trials [47]. Nevertheless, studies report benefits for healing in animal models of crushed muscles, faster tendon-to-bone healing, improved gut healing in models of short bowel syndrome, as well as accelerated tissue healing in wounds [48, 49, 50, 51, 52].
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TB-500
TB-500 is a synthetic variant of thymosin beta-4 (TB4), a peptide consisting of 43 amino acids that is prevalent in various human cells. TB4 was initially isolated from bovine thymus gland extract in 1981 by Low and Goldstein. Ongoing research is investigating its prospective impact on cell migration, particularly the movement of progenitor cells crucial for tissue repair [53].
This peptide may help healing by also facilitating the formation of new blood vessels, stem cell maturation, cell survival across various types, and inflammation reduction [54, 55].
Synthetic TB4 has been studied primarily for the healing of the eye cornea [56]. The peptide may speed up wound healing in subjects with venous ulcers by 45% [57]. Some trials also suggest it may improve heart muscle function and recovery in subjects who suffered a heart attack and were treated with endothelial progenitor cells [58].
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Longevity Peptides
Longevity and anti-aging represents one of the most popular fields of peptide research, with the following two compounds garnering considerable interest around the world by researchers.
Here's two popular peptides with longevity research applications:
Epithalon
Epithalon, also referred to as Epitalon or AEDG peptide, is a tetrapeptide composed of the amino acids Alanine-Glutamate-Aspartate-Glycine (Ala-Glu-Asp-Gly). It was derived from a crude pineal gland extract known as epithalamin [59].
This peptide is purported to enhance telomerase activity, a mechanism crucial for maintaining and elongating telomeres—protective structures located at the chromosomal termini. Extended telomeres are correlated with enhanced cellular longevity and a deceleration in aging processes [60, 61].
Several trials suggest a potential longevity promoting effect of epithalon, with one trial in 266 study volunteers reporting x1.6-1.8 reduced mortality compared to controls [62, 63, 64].
Additionally, preclinical investigations have explored epithalon's potential in inhibiting tumor genesis, mitigating oxidative stress, and bolstering endocrine as well as immune system functionality [65, 66, 67].
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NAD+
NAD+ (nicotinamide adenine dinucleotide) is a universal coenzyme present in every cell, playing key roles in electron transport and signaling. Its cellular levels decrease with aging. Thus, modulating NAD+ levels is considered an option that could potentially extend lifespan and bolster neurocognitive function [68].
Predominantly found in mitochondria, NAD+ facilitates crucial cellular processes like protein modification and sirtuin enzyme activities, impacting cell growth, energy metabolism, stress resistance, inflammation management, and neuronal function [69].
Studies in mice have shown that boosting NAD+ metabolism may mitigate premature aging diseases and extend lifespan [70].
For example, a 12-month rodent study demonstrated that administering the NAD+ precursor (nicotinamide mononucleotide) NMN curbed weight gain, enhanced energy metabolism, and improved insulin sensitivity[71].
Yet, more research is needed to establish whether such benefits may also translate to clinical trials.
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Reproductive Health Peptides
Peptides for reproductive health work to improve fertility and libido in a variety of ways, such as by interacting with the melanocortin system or the hypothalamic-pituitary-gonadal (HPG) axis.
Here are some of the more notable compounds in this realm:
PT-141
PT-141, also known as bremelanotide, is a cyclic heptapeptide that acts as an agonist to melanocortin receptors (MCRs) present in various organs and systems. It replicates the action of endogenous alpha-melanocyte stimulating hormone (alpha-MSH) [72].
Upon administration, PT-141 activates MCRs with increased activity towards the melanocortin 4 receptors in the brain, stimulating sexual function, energy balance, and appetite.
Consequently, PT-141 has shown a notable enhancement in sexual desire and has received approval for use in premenopausal women diagnosed with hypoactive sexual desire disorder (HSDD) [73].
Further studies also underscore the potential of PT-141 in significantly elevating libido and sexual desire in males, alongside prolonging the duration of erections.
Interestingly, PT-141 has been posited by some researchers as a viable alternative for males who exhibit no response to PDE5 inhibitors such as Viagra (sildenafil) [74].
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Kisspeptin-10
Kisspeptin-10 is a decapeptide that belongs to the larger kisspeptin family, encoded by the KISS1 gene in hypothalamic cells. Kisspeptins are peptides crucial for reproductive regulation, interacting with the G protein-coupled receptor, GPR54 [75].
As such, kisspeptin-10 can modulate the rhythmic release of gonadotropin-releasing hormone (GnRH), prompting the pituitary gland to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones trigger testosterone (T) synthesis in the testes, enhancing fertility and boosting T levels [76].
For example, a clinical trial has shown that kisspeptin-10 infusion significantly increased mean serum T levels in healthy male participants from 479ng/dl to 692ng/dl in under 23 hours [77].
Yet, long-term studies are scarce, raising concerns about potential receptor desensitization with repeated administration, which may reduce the peptide’s effectiveness, lessen responsiveness to natural kisspeptins, and suppress natural T synthesis.
Given these uncertainties, careful dosage is advised in research involving kisspeptin-10 [76].
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Gonadorelin
Gonadorelin is a synthetic version of gonadotropin-releasing hormone (GnRH), mirroring the natural hormone in structure and function. When administered, it crosses the blood-brain barrier (BBB), prompting the pituitary gland to release LH and FSH [78]. It is clinically used to trigger ovulation in women with menstrual irregularities stemming from hypothalamic issues and to assess HPG axis function [79].
Studies indicate that gonadorelin can enhance HPG axis activity in men with hypothalamic dysfunction and insufficient GnRH levels [80]. According to the research, it also effectively elevates T levels and improves fertility in men with normal testicular and pituitary gland functionality [81].
For example, a study has shown that a regimen of 200mcg of gonadorelin over three days can stimulate normal LH and FSH production in a male patient with impaired pituitary and testicular function due to prior anabolic-androgenic steroid (AAS) use, tripling his testosterone levels beyond the 300ng/dl benchmark [82].
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Nootropic Peptides
Nootropic peptides exert their memory and concentration-boosting properties by interacting with various neurotransmitters and neurotrophic factors in the brain. To do so, they need to have the ability to pass through the blood–brain barrier (BBB).
Here are a couple of notable examples that have been engineered to do just that:
Semax
Semax is a synthetic peptide composed of a four amino acid fragment (Met-Glu-His-Phe) from the adrenocorticotropic hormone (ACTH) and a Pro-Gly-Pro fragment attached at the C-terminus [83]. It can pass the BBB to reach the central nervous system without exerting hormonal effects [84].
Once there, Semax appears to interact with various neurotrophic factors in the nervous system that support the growth, survival, and maintenance of neurons. It also interacts with several neurotransmitters [85].
It is approved in Russia for neuroprotective and cognitive-enhancing agents in settings of ischemic stroke, encephalopathy, optic nerve atrophy, and other indications, such as cognitive disorders [86]. The peptide also appears to provide nootropic effects in otherwise healthy individuals [87].
For example, a trial in fatigued volunteers who have worked eight-hour shifts reported that a single intranasal administration of Semax at 16mcg/kg of body weight resulted in a sustained nootropic effect lasting up to 24 hours. The treatment group had 71% correct answers on a memory test compared to 41% of those in the control group [87].
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Selank
Selank is another heptapeptide developed in the 1990s and approved as an anxiolytic by the Russian Federation Ministry of Health in 2009 [86].
It is a synthetic analog of the endogenous human tetrapeptide tuftsin (threonine-lysine-proline -arginine) and contains a Pro-Gly-Pro fragment at its C-terminus, which allows it to pass the BBB [88].
Selank has a pronounced effect on opioid, serotonergic, and GABA signaling. These mechanisms are likely central to Selank's ability to reduce stress and anxiety levels [88, 89].
Studies in subjects with generalized anxiety disorder (GAD) report that Selank may be non-inferior to medazepam, meaning that the two agents may produce comparable anxiolytic benefits [89].
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Immune System Peptides
Below, we outline two of the more notable peptides that may aid the immune system in tackling infections and inflammation:
Thymosin Alpha-1
Thymosin alpha-1 (TA-1) is a vital immune regulator derived from the thymus gland, with secretion peaking in childhood and diminishing from puberty onwards [90].
Based on research, TA-1 oversees immune cell production and maturation and can replenish white blood cells, potentially aiding immunity even in cases of thymus impairment [91].
Low levels of thymosin alpha-1 may result in weakened immune function and heightened disease susceptibility. Thus, by enhancing the adaptive immune response, TA-1 aids in tackling various infections [92].
Additionally, it appears to stimulate humoral immunity, elevate levels of several interferons and interleukins, and is proposed as a vaccine adjuvant to bolster T-cell-dependent antibody production, improving vaccine efficacy [93].
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KPV
KPV, standing for lysine-proline-valine, is identified as the C-terminal end of alpha-MSH. The latter is thought to contribute to several physiological processes, including melanogenesis, appetite modulation, and sexual desire [94].
Its C-terminal fragment (e.g., KPV) may also have anti-inflammatory effects such as the regulation of NF-κB activation, T-cell proliferation, and inflammatory cell migration [95].
Further, several studies have suggested that alpha-MSH has anti-inflammatory and wound-healing effects, which may also translate to KPV [96]. For example, preclinical studies suggest improved corneal epithelial wound healing in rabbits [97].
Yet, more research is needed to evaluate its potential in clinical settings.
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Sleep Peptides
One of the most notable peptides for sleep is delta sleep-inducing peptide (DSIP).
Here are the most important facts for researchers to consider:
DSIP
DSIP is a nonapeptide discovered in 1974 by Swiss scientists, who found it to trigger delta sleep when administered to laboratory test animals [98].
Delta sleep is the phase of slow-wave sleep that manifests with delta waves recorded via electroencephalogram (EEG). DSIP appears to increase delta activity in this phase, which is deemed a marker of enhanced sleep quality, as it is linked to minimized external stimuli perception, promoting restorative sleep and minimizing easy awakenings [99].
Moreover, DSIP is reported to positively influence stage-4 or REM sleep, the dream phase, which is crucial for emotional memory processing and consolidation [100].
DSIP's mechanism is speculated to involve interaction with N-methyl-D-aspartate (NMDA) or alpha 1-adrenergic receptors and potentially engaging with neurons through the mitogen-activated protein kinase (MAPK) pathway, a key regulator of intercellular signaling [101].
Clinically, DSIP has exhibited promise in normalizing sleep cycles and alleviating narcolepsy [100]. It is also being explored for treating withdrawal symptoms in cases of alcohol and opiate addiction [102].
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List of Peptides | Verdict
Research peptides are versatile molecules with a wide range of potential applications. Many compounds have been studied extensively for benefits such as weight loss, muscle growth, skin care, healing and injury recovery, longevity promotion, reproductive health, cognitive enhancement, immune health, and sleep improvement.
Professional researchers looking to investigate the vast potential of peptides are advised to source strictly research-grade compounds from a reputable online vendor.
Our experienced team members highly recommend Limitless Life as the most trusted supplier of high-quality peptides for the research community.
David Warmflash, M.D.