Peptide Research News

This journal listing includes several articles touching on obesity pharmacotherapy, most notably a systematic review and meta-analysis of subcutaneous semaglutide's effects on weight loss and inflammatory markers in adults with overweight or obesity without diabetes. Additional items examine GLP-1 receptor agonists from a rheumatological perspective and self-medication with GLP-1 drugs among Brazilian adults. The listing also covers broader obesity research, including bariatric surgery positioning and epidemiological studies.

New research suggests that semaglutide reduces the risk of major adverse cardiovascular events (MACE) not only through weight loss but also by lowering systemic inflammation. A study of over 17,000 patients found that reductions in the inflammatory biomarker hs-CRP accounted for roughly 28% of the drug's cardiovascular benefit. This indicates that semaglutide's mechanism for heart protection involves direct anti-inflammatory effects independent of glycemic control or body weight reduction.

Swedish biotech Oxcia has promoted Dr. Sandra Ekstedt to Preclinical Director to advance the development of OXC-201, a first-in-class oral inhibitor targeting the OGG1 enzyme. The drug candidate is designed to treat Idiopathic Pulmonary Fibrosis (IPF) by blocking the interaction between damaged DNA and OGG1, thereby preventing inflammation and fibrosis. Dr. Ekstedt, a specialist in respiratory diseases, will finalize the preclinical program and investigate the drug's ability to alleviate cough and improve lung function.

Nykode Therapeutics has released new preclinical and manufacturing data for VB10.NEO, an individualized neoantigen therapy. The results indicate that their DNA-based platform induces stronger and more durable T-cell responses compared to traditional peptide vaccines. Additionally, the company reported improvements in manufacturing scalability and timelines, positioning the asset for strategic partnerships.

A review in Nature Reviews Disease Primers examines the biological underpinnings and clinical management of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG). It highlights recent genetic advances implicating the hormone GDF15 and the protein IGFBP7 as key drivers of the condition, acting through receptors in the brainstem. These findings suggest a placental origin for the disease and offer potential targets for future therapeutic development.

New clinical trial data for Eli Lilly's 'triple-G' drug, retatrutide, indicates that the medication effectively lowers blood sugar and aids in weight loss. However, the results leave open questions regarding the drug's potential cardiovascular benefits, specifically whether it offers heart protection comparable to other established therapies.

Researchers have developed a battery-free smart contact lens capable of monitoring intraocular pressure and delivering medication on demand. The device uses changes in corneal shape to trigger the release of drugs from a microfluidic chamber, aiming to improve adherence and treatment precision for glaucoma patients.

A study by the TransCODE Consortium presents a consensus landscape of the human proteome by validating the translation of non-canonical open reading frames (ncORFs). Analyzing over 95,000 proteomics experiments, researchers found that roughly 25% of 7,264 studied ncORFs produce detectable microproteins, which they term 'peptideins'. The study introduces an evolutionary framework to identify functional microproteins and confirms the biological necessity of one such peptidein derived from long non-coding RNA.

New real-world data presented at ARVO challenges the historical belief that Thyroid Eye Disease (TED) stabilizes after 18 months. Analyzing records of over 34,000 patients, researchers found that nearly 30% experienced disease progression years after their initial diagnosis. These findings suggest that the clinical progression of TED may not strictly follow the traditional Rundle's Curve model.

A retrospective study published in Scientific Reports in April 2025 by Yao et al. found that adding thymosin alpha-1 to lenvatinib plus sintilimab extended median overall survival to 16 months versus 11 months in patients with unresectable hepatocellular carcinoma. The thymosin alpha-1 group also showed higher objective response rates (55.8% vs 34.7%) and longer progression-free survival. The findings add to growing evidence for the immunomodulatory peptide as a useful adjunct in cancer combination regimens.

A comprehensive 2025 narrative review in Current Reviews in Musculoskeletal Medicine by McGuire et al. synthesized the evidence on BPC-157 for musculoskeletal injury, detailing its pro-angiogenic and anti-inflammatory mechanisms. The authors documented only three small human pilot studies to date, including a 2025 first-in-human IV infusion trial in two healthy adults that reported no adverse events. Despite robust preclinical signals across tendon, muscle, and bone repair, the review concluded BPC-157 remains investigational pending well-designed clinical trials.

A 2025 study in Experimental & Molecular Medicine by Kong et al. found that the mitochondrial-derived peptide MOTS-c declines as pancreatic islet cells age and that exogenous MOTS-c treatment can reduce this senescence. Lower circulating MOTS-c levels were observed in type 2 diabetes patients compared to healthy controls. In aged mice, MOTS-c treatment improved glucose intolerance and modulated nuclear gene expression linked to beta-cell aging. The findings position MOTS-c as a potential therapeutic target for age-related metabolic disease.

On September 19, 2025, the FDA granted accelerated approval to FORZINITY (elamipretide HCl), making it the first treatment ever approved for Barth syndrome and the first drug to directly target mitochondrial dysfunction. Elamipretide — originally known in research as the SS-31 peptide — works by stabilizing cardiolipin in the inner mitochondrial membrane. The approval covers adult and pediatric patients weighing at least 30 kg and is supported by the TAZPOWER trial showing improved knee extensor muscle strength.

Researchers developed a machine learning tool called OBSCORE to predict the risk of obesity-related complications using data from approximately 200,000 individuals. Validated in the SURMOUNT-1 trial, the study showed that tirzepatide effectively reduced these predicted risks across different baseline risk groups, regardless of the patient's initial risk score.

A genome-wide association study of nearly 28,000 patients identified genetic variants in the GLP1R and GIPR genes that influence the efficacy and side effects of GLP-1 receptor agonists. A specific missense variant in GLP1R was linked to significantly greater weight loss, while variations in both GLP1R and GIPR were associated with the likelihood of experiencing nausea or vomiting. These findings suggest that genetic screening could help predict individual patient responses to popular obesity drugs like semaglutide and tirzepatide.

This opinion piece criticizes Health Secretary RFK Jr. for reportedly moving to reverse the FDA's 2023 safety classification of certain peptides, specifically BPC-157 and GHK-Cu. The author argues that returning these substances to a status that allows compounding pharmacies to produce them ignores the lack of clinical trial data and poses significant risks to the public.

Researchers have identified neuraminidase 1 (NEU1) as a novel regulator that suppresses the liver's response to glucagon, a peptide hormone that raises blood sugar. In mouse models, the absence of NEU1 exacerbated glucagon-driven glucose production, whereas its overexpression reduced hyperglycemia. The study also identified two compounds, α-hederin and oleanolic acid, that mimic this protective effect by stabilizing NEU1.

A study published in Nature identifies a link between insulin-regulated serine metabolism and peripheral neuropathy. Researchers found that low levels of the non-essential amino acids serine and glycine drive nerve damage in diabetic mice. The study suggests that dietary serine supplementation could serve as a potential therapeutic intervention for diabetic neuropathy.

Nature Medicine reports on the development of a new oral GLP-1 drug designed to treat obesity. Unlike current peptide-based treatments that require subcutaneous injection, this non-peptide version is administered as a pill, offering easier storage and usage. The advancement aims to improve accessibility and adherence for patients requiring weight management therapies.

Landmark cardiovascular/renal outcome trials show GLP-1 receptor agonists lower the risk of major cardiovascular events and kidney failure — benefits now reported to extend to type 1 diabetes populations, broadening the therapeutic case for the class beyond weight loss and glycemic control.

The GLP-1 receptor agonist efficacy ladder keeps climbing: semaglutide (~15% mean weight loss), the dual GIP/GLP-1 agonist tirzepatide (~21%), and triple agonists such as retatrutide (glucagon/GIP/GLP-1) reporting even greater reductions in Phase 2. The 2026 pipeline is crowded with next-generation candidates aiming for greater efficacy, oral delivery, and muscle preservation.

A large study published in Annals of Oncology analyzed health data from over 229,000 obese, non-diabetic people and found an association between GLP-1 receptor agonist use and reduced risk of obesity-related cancers, including pancreatic and colorectal cancers. The research adds to growing interest in GLP-1 drugs like Ozempic, Wegovy, Zepbound, and Mounjaro beyond diabetes and weight loss. Experts note that with hundreds of millions of people expected to take these drugs, even modest risk reductions could have major public health implications.

This study investigates the role of the cGMP-PKG signaling pathway in mitigating calcific aortic valve disease (CAVD). Researchers found that this pathway is suppressed in patients with CAVD and that pharmacological activation using the peptide hormone BNP, as well as vericiguat and sildenafil, attenuates calcium deposition in valve cells. The mechanism involves PKGI-mediated autophagy via ULK1 phosphorylation, suggesting vericiguat as a potential therapeutic candidate.

A study published in Translational Psychiatry utilized a rat model of maternal separation to investigate cognitive impairment resembling schizophrenia. Researchers found that cognitive deficits were linked to mitochondrial dysfunction and reduced levels of NAD+ and SIRT3 in the hippocampus. The study demonstrated that supplementing with nicotinamide (NAM), a form of Vitamin B3, successfully restored the NAD+/SIRT3 axis, improved synaptic plasticity, and reversed cognitive decline.

Researchers have proposed an updated framework called 'NAD World 3.0' to explain mammalian aging, highlighting the critical roles of nicotinamide mononucleotide (NMN) and extracellular nicotinamide phosphoribosyltransferase (eNAMPT). This concept emphasizes that the decline of systemic NAD+ is a key driver of aging and suggests that inter-tissue communication, mediated by NMN transport and eNAMPT activity, regulates longevity. The theory updates previous versions by incorporating new findings on how these molecules maintain metabolic feedback loops between the hypothalamus and peripheral tissues.

A study in *Translational Psychiatry* found that female mice lacking the ZDHHC7 gene exhibited resilience to chronic stress, characterized by reduced depression-like behaviors and preserved hippocampal structure. This resilience was associated with a significant upregulation of the neuropeptide cortistatin in the brain, suggesting a potential protective role for this peptide against stress-induced psychiatric disorders.

A comprehensive observational study published in Nature Medicine analyzed the health impacts of GLP-1 receptor agonists, identifying 42 potential benefits and 19 potential risks. The research highlights that these drugs affect multiple organ systems beyond their primary use in diabetes and weight loss. While confirming protective effects for the heart and kidneys, the study also flagged rare but serious safety concerns, including gastrointestinal conditions and potential neurological risks.

Researchers investigated the anti-biofilm peptide DJK-5 in combination with antibiotics against polymicrobial infections. In vitro and in vivo studies showed that DJK-5 sensitizes Staphylococcus aureus to colistin and Pseudomonas aeruginosa to daptomycin, overcoming the typical resistance of these pathogens in co-biofilms.

Research published in Cell Death & Disease demonstrates that Nicotinamide mononucleotide (NMN) can improve the mitochondrial stress response in Alzheimer's disease models. The study found that NMN supplementation restores NAD+ levels and activates the ATF4-dependent mitochondrial unfolded protein response (UPRmt), which helps clear toxic protein aggregates. In mice models, this mechanism reduced synaptic loss, brain atrophy, and memory deficits, suggesting NMN could be a viable therapeutic strategy for neurodegeneration.

Research published in Nature Communications indicates that prenatal exposure to Bisphenol A (BPA) is linked to autism spectrum disorder (ASD) symptoms in males through the disruption of brain aromatase. Using a birth cohort and mouse models, scientists found that BPA suppresses aromatase, leading to ASD-like behaviors and brain changes. The study further reports that treatment with 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid found in royal jelly, successfully alleviated these neurological and behavioral deficits in mice.

A Nature Communications study shows that medullary thyroid cancer (MTC) expresses CGRP, which shapes an immunosuppressive tumor microenvironment by altering dendritic cell development via cAMP/KLF2 pathways and impairing T cell activity. A CGRP receptor antagonist reversed these effects in vitro. The findings propose the CGRP receptor as a potential therapeutic target in MTC.

A peer-reviewed study in Scientific Reports examined whether semaglutide and tirzepatide reduce alcohol consumption in people with obesity. Researchers analyzed ~68,250 Reddit posts about GLP-1 and GLP-1/GIP drugs and ran a remote study with 153 drinkers (BMI ≥30) taking either drug or no medication. Alcohol-related posts (n=1,580) were 71% positive regarding reduced cravings and desire to drink. The participant study found significantly lower alcohol intake, drinks per episode, binge drinking odds, and AUDIT scores versus baseline and controls. The authors present this as real-world evidence supporting possible efficacy for alcohol use disorder comorbid with obesity.

Researchers utilized cryo-electron microscopy to solve the structures of the human melanocortin-3 (MC3R) and melanocortin-5 (MC5R) receptors bound to various agonists. The findings reveal how the endogenous peptide γ-MSH achieves selectivity for MC3R through specific C-terminal interactions, while α-MSH binds non-selectively to MC5R. Additionally, the study characterizes the binding mode of a potent synthetic agonist, PG-901, and confirms the presence of calcium ions within the receptor structures.

Japanese researchers developed Osteo-DISCO, a tissue-clearing method enabling 3D visualization of nerves and blood vessels in murine bone. They identified specific nerve entry sites in long bones and showed that surgical ablation of these nerves impaired bone formation and regeneration. Administering CGRP, a sensory neuropeptide, suppressed the nerve-ablation-induced bone loss, and in vitro data showed CGRP directly stimulates osteoblast activity, supporting sensory nerves as regulators of osteogenesis via CGRP.

A study in Nature Communications demonstrates that a combination therapy using the peptide-based drugs ActRIIB-Fc and anamorelin can reverse cancer cachexia and improve survival in a mouse model of lung cancer. While anamorelin successfully restored appetite, only the dual treatment effectively increased lean mass and physical activity. Crucially, the therapeutic benefits were found to be specific to female mice, dependent on ovarian function, and correlated with Activin A expression levels in human female patients.

A study published in Translational Psychiatry utilized genetic data from approximately 480,000 individuals in the UK Biobank to investigate the relationship between the oxytocin pathway, severe mental disorders, and metabolic health. The researchers developed polygenic scores specific to the oxytocin system and found statistically significant associations with schizophrenia, bipolar disorder, type 2 diabetes, and cardiovascular disease risk factors. These findings suggest that genetic variations in the oxytocin pathway may partially explain the high co-occurrence of metabolic and cardiometabolic conditions in patients with severe mental illness.

This review highlights the role of the cyclic peptide melanin-concentrating hormone (MCH) in regulating energy balance, sleep, and emotional states. It details how MCH acts through the MCHR1 receptor to stimulate food intake, reduce energy expenditure, and promote weight gain. The authors suggest that targeting MCHR1 with agonists or antagonists offers promising therapeutic potential for treating obesity and associated metabolic disorders.

A study published in Scientific Reports found that exposure to bright light in the early evening can reduce the sleep-disrupting effects of light exposure later at night. Researchers observed that while late-evening light typically suppresses melatonin and alertness, these negative physiological impacts were mitigated when participants were exposed to bright light earlier in the evening.

Researchers have identified a novel cell-penetrating peptide named CPP-Ts in the venom of the Tityus serrulatus scorpion. This peptide modulates intracellular calcium channels by activating nuclear InsP3 receptors, which increases the contraction frequency of cardiomyocytes. Furthermore, the team developed a synthetic sub-fragment of the peptide (residues 14–39) that retains nuclear-targeting capabilities but lacks toxic pharmacological activity, demonstrating its potential as a targeted drug delivery vehicle for cancer cells.

A genome-wide association study published in Nature Communications has identified a genetic link between hyperemesis gravidarum (HG), a severe form of pregnancy sickness, and two specific genes: GDF15 and IGFBP7. The research found that variants at chr19p13.11 and chr4q12 loci are associated with the condition, implicating these genes which are known to influence placentation, appetite regulation, and cachexia. While further study is needed to prove causality, these findings suggest that hormonal signaling involving these peptides may drive the severe nausea and vomiting experienced in HG.

This review article updates the 'NAD World' concept, highlighting how the enzyme eNAMPT and the molecule NMN facilitate communication between the hypothalamus, adipose tissue, and skeletal muscle to regulate aging. It posits that adipose tissue-derived eNAMPT is critical for maintaining NAD+ levels, which in turn activates SIRT1 to control longevity. This framework provides a biological basis for developing anti-aging interventions.

Research from Columbia University indicates that the bone-derived hormone osteocalcin is necessary for exercise capacity in mice, monkeys, and humans. The study found that osteocalcin levels rise during physical activity, signaling muscles to uptake more glucose and nutrients. Notably, administering osteocalcin to older mice restored their exercise performance to levels comparable to young mice.

This clinical study investigated how a state of ketosis affects appetite-regulating hormones following significant weight loss. Researchers found that maintaining ketosis via a very-low-energy diet (VLED) suppressed the typical post-weight loss surge in ghrelin, a hormone known to stimulate hunger. Additionally, participants in ketosis exhibited lower levels of amylin and leptin compared to their levels after refeeding, suggesting that ketogenic diets may help mitigate the physiological drive to regain weight.

This review article examines human genetic evidence supporting the role of the corticotropin-releasing factor (CRF) system in stress, anxiety, and depression. It highlights that genetic variants in the CRF1 receptor gene interact with adverse environmental factors to predict the risk of psychiatric disorders.

A review in Nature Neuroscience refines the 'neurotrophin hypothesis of depression' by examining the complex biology of Brain-Derived Neurotrophic Factor (BDNF). It highlights that while BDNF signaling is necessary for antidepressants to work, genetic disruption of these pathways does not inherently cause depression. The authors emphasize the opposing roles of the precursor proBDNF and mature mBDNF, suggesting that the balance between these peptides, rather than BDNF levels alone, is critical for understanding mood disorders.

A Swedish national cohort study of 14,694 people with bipolar disorder found that semaglutide use was associated with a lower risk of psychiatric hospitalization, with no concerning safety signals such as suicidality. Published in Acta Psychiatrica Scandinavica, the study analyzed 2009-2024 registry data from patients using diabetes medications. This is the first study to evaluate GLP-1 receptor agonists in people with bipolar disorder, despite frequent co-occurrence of diabetes, obesity, and bipolar disorder.

A Nature Communications study reports that calcitonin gene-related peptide (CGRP), a neurotransmitter peptide, contributes to an immunosuppressive tumor microenvironment in medullary thyroid cancer. The findings suggest CGRP signaling may help the cancer evade immune attack and could represent a therapeutic target. The article metrics page itself is only a wrapper, but the underlying paper centers on CGRP biology in cancer immunology.

This article aggregates research findings on neuropeptides, specifically focusing on the role of Orexin-A and Orexin-B in the brain. It highlights how Orexin-A regulates dopamine D2 receptors within the mesolimbic circuit and discusses the broader function of orexin signaling in promoting initial alcohol consumption. The text provides context on the exclusive expression of these neuropeptides in hypothalamic neurons and their interaction with specific G-protein coupled receptors.

Researchers used mRNA display to discover macrocyclic peptides that bind to the BamA protein in Gram-negative bacteria. These peptides inhibit outer membrane protein assembly, effectively killing the bacteria by blocking an essential cellular process. Molecular dynamics simulations indicate that these peptides function via a previously undescribed mechanism, trapping BamA in a conformation that halts the initiation of assembly.

Researchers used computational methods to identify dynobactin A, a novel peptide antibiotic from *Photorhabdus australis* that targets the BamA protein in Gram-negative bacteria. Unlike the related darobactin, dynobactin features two unlinked rings and binds uniquely to the BamA lateral gate. The peptide demonstrated efficacy in mouse models of systemic *E. coli* infection, marking it as a promising candidate for drug development.