Peptide Research Database
Access 4,887 peer-reviewed studies, clinical trials, and research papers on peptides. Filter by key research, study type, compound, and category. Direct links to full PubMed entries for comprehensive, evidence-based exploration.
Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study.
In a clinical study, it supports evidence-based decision-making for long-term weight management treatment in the UK, and beyond, while offering a scalable platform for future therapeutic evaluations.
Annemans L, Johansson E, Spaepen E, van Hest N, Grist J, Zimner-Rapuch S, Wilding JPH
This study presents an updated health economic model for evaluating the long-term cost-effectiveness of interventions in overweight and obesity, integrating new clinical evidence from the SURMOUNT clinical trial programme and methodological advancements in type-2 diabetes and obstructive sleep apnea (OSA) modelling. An updated individual patient simulation model evaluated the costs and long-term clinical outcomes of tirzepatide (5, 10, 15.0 mg) versus diet and exercise (D&E) alone in patients with a body mass index (BMI) ≥30 kg/m2 (obesity), or BMI ≥27 to <30 kg/m2 (overweight) + ≥1 obesity-related complication with a UK healthcare perspective. Key improvements over a previously published model were introduced, including modelling remission and progression of OSA, capturing realistic patterns of D&E discontinuation, incorporating HbA1c as a continuous cardiometabolic endpoint and transition to R-based implementation over VBA. Primary results include incremental cost-effectiveness ratios (ICERs; cost/QALY), costs, life years gained and quality-adjusted life years (QALYs). Secondary outcomes including clinical outcomes, random seed and cohort convergence, deterministic sensitivity results and run time were also calculated. The refined model predicted that all tirzepatide doses were cost-effective compared to D&E at a £20,000/QALY gained WTP (willingness-to-pay) threshold (ICERs: £8,327-£10,157). Refined estimation of long-term D&E discontinuation and OSA remission likely contributed to lower incremental costs, higher QALYs, and reduced ICERs compared with the previous model, aligning outcomes more closely with expected benefits from weight management treatment. Transitioning to R-based implementation reduced run time (e.g. by 4.52 h for deterministic sensitivity analyses) and enhanced model stability in all analyses conducted. This enhanced economic model represents a significant advancement in the evaluation of obesity pharmacotherapy, designed to enhance clinical relevance, technical robustness, and increase usability. It supports evidence-based decision-making for chronic weight management treatment in the UK, and beyond, while offering a scalable platform for future therapeutic evaluations.
Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial.
In a case report, this supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD). Evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity.
Johansson E, Wilding JPH, Upadhyay N, van Hest N, Kirk M, Spaepen E, Zimner-Rapuch S, Annemans L, Bays H
This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]). This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses. Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD). Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD).
GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.
In a research review, personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management.
Chikatimalla R, Shah A, Shah T, Perry G, Banker H, Aggarwal K, Jain R
To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management.
Targeting the NAD+-SIRT3 axis to mitigate metabolic memory in diabetic kidney disease.
In an animal study, translationally, selective kidney-targeted SIRT3 activators, integration with renoprotective therapies, and validated SIRT3 activity biomarkers are priorities to determine if targeting the NAD+-SIRT3 axis can reduced metabolic memory and slow DKD progression.
Zhang Y, Wang Y, Qiao Y, Liu L, Zhao H, Jin Q, Peng L, Li P
Metabolic memory-the persistent risk of diabetic complications after early hyperglycemia-drives progressive renal injury in diabetic kidney disease (DKD) via sustained oxidative stress, inflammation, and epigenetic reprogramming. We synthesize clinical and experimental evidence showing the nicotinamide adenine dinucleotide (NAD+)-SIRT3 (sirtuin 3) axis as a central mechanistic hub linking mitochondrial dysfunction to epigenetic and inflammatory programs in DKD metabolic memory, while evaluating restoration strategies. Integrating data from preclinical, cellular, and human studies, we review SIRT3 biology, compartment-specific renal effects (proximal tubule, podocyte, endothelium), downstream targets, and NAD+/SIRT3-modulating interventions. Key findings show consistently reduced renal SIRT3 expression and activity, driving mitochondrial hyperacetylation, impaired fatty-acid oxidation, persistent ROS, NLRP3/NF-κB-mediated inflammation, and profibrotic signaling. Preclinical NAD+ restoration or SIRT3 activation (e.g., NMN, NR, honokiol, metformin, SGLT2 inhibitors) ameliorates mitochondrial dysfunction, oxidative stress, fibrosis, and albuminuria; however, clinical evidence regarding renal endpoints and SIRT3 engagement biomarkers remains scarce. Translationally, selective kidney-targeted SIRT3 activators, integration with renoprotective therapies, and validated SIRT3 activity biomarkers are priorities to determine if targeting the NAD+-SIRT3 axis can mitigate metabolic memory and slow DKD progression.
Investigation of the stability profile of therapeutic α-MSH analogue: Insights from liquid chromatography-high resolution mass spectrometry analysis of afamelanotide.
In lab experiments, researchers studied the chemical stability of afamelanotide (melanotan-1), an approved drug for a rare light sensitivity disorder. By tracking how the peptide breaks down under various storage conditions, they identified the specific degradation pathways that could reduce its effectiveness. This work helps ensure the drug maintains its potency and safety throughout its shelf life.
Chawathe A, Sharma N
Afamelanotide, also known as melanotan-1, is a synthetic 13-amino acid peptidomimetic of α-melanocyte stimulating hormone (α-MSH), and is a critical peptide orphan drug used for the management of erythropoietic protoporphyria. It contains norleucine and D-phenylalanine at positions 4 and 7, in place of methionine and L-phenylalanine, respectively as found in endogenous peptide. Therapeutic peptide stability profiling is crucial in drug development because chemical and physical degradation during storage alters structural properties, potentially reducing efficacy and compromising safety by preventing target engagement. Stability testing for synthetic peptides is performed by following the International Council for Harmonisation (ICH) guidelines Q1A(R2) and Q5C. The current work endeavours to explore afamelanotide's degradation pathways under various chemical and physical stress conditions: acidic, basic, neutral, and oxidative stress, UV light exposure, and increased temperature at 60⁰C. The study demonstrated that afamelanotide undergoes degradation under all applied stress conditions with the generation of fourteen different degradation products (DPs) which were separated by gradient reversed-phase HPLC on a Zorbax SB C18 column (300 Å, 4.6*150 mm, 3.5 µm) and the method was validated according to the ICH Q2(R1) guideline. To enable comprehensive characterization, the analysis was coupled with ultra-high-performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS), where collision-induced dissociation yielded abundant and accurate fragmentation patterns, enabling the detailed structural elucidation of the products. While this work has identified several degradation pathways such as truncation, methylation, deacetylation, and oxidation, it also establishes complete stability profile of α-MSH analogue, thus offering key insights for the rational design of robust drug formulations.
Finding functional gaps: integrative analysis of VPAC1- and VPAC2-mediated signalling pathways in human lymphocytes
In lab experiments, in Jurkat cells, both receptors induce a shift in its basal state; however, changes do not persist during TCR-driven activation, resulting in largely convergent effector responses.
Cabrera-Martín A, Arribas-Castaño P, Castro-Vázquez D, Tecza K, Pérez-García S, Martinez C, Khamlichi CE, Morisset-López S, Juarranz Y, Gutiérrez-Cañas I, Villanueva-Romero R.
Abstract Background Vasoactive Intestinal Peptide (VIP) is a pleiotropic neuropeptide regulating diverse cellular and physiological processes. Its functions are primarily mediated through two G protein–coupled receptors, VPAC1 and VPAC2. The aim of this study was to perform an integrative analysis of VPAC receptor signalling, encompassing receptor–G protein coupling, second messenger production, kinase activation and transcriptional responses in T cells. Experimental Approach : Receptor interactions with Gα subunits were analysed using BRET assays. Stable Jurkat T-cell lines overexpressing VPAC1 (J-OEV1) or VPAC2 (J-OEV2) were generated. VPAC-dependent intracellular signalling in these cells was assessed by measuring cAMP and Ca²⁺ levels, performing phospho-kinase arrays and Western blot analyses, and evaluating immune mediator expression, cell viability, and proliferation. Results VPAC1 showed interaction with both Gαs and Gαq subunits, whereas VPAC2 preferentially interacted with Gαs. In Jurkat cells, both receptors overexpression enhanced cAMP signalling, while increased Ca²⁺ responses were restricted to VPAC1. In both J-OEV1 and J-OEV2 cells, VIP treatment reduced phosphorylation of inflammatory kinase-associated proteins. Overexpression of either receptor induced distinct basal transcriptional profiles of transcription factors and cytokines, which were further modulated by CD3/CD28-activation and VIP. While proliferation was not altered with overexpression, J-OEV2 showed a reduced redox metabolism at 72h. Conclusion This study aimed to identify functional differences between VPAC1 and VPAC2 signalling and reveals reproducible subtype-specific differences at early signalling. In Jurkat cells, both receptors induce a shift in its basal state; however, changes do not persist during TCR-driven activation, resulting in largely convergent effector responses.
Temporal persistence of unidirectional rhythmic coupling is inversely associated with salivary oxytocin change during facilitated drum circles in children
This study found larger preregistered studies are needed to determine whether temporal persistence of directional coupling provides a biologically relevant marker of engagement during group music-making. In a school-based pilot study (n = 11; aged 9–10 years), we examined whether the temporal structure of facilitator–child rhythmic interaction relates to pre–post changes in salivary oxytocin.
Kikuchi M, Yoshimura Y, Tanaka S, Okanemasa Y, Furuhara K, Higashida H, Tsuji C.
Abstract Facilitated drum circles may promote social bonding in children, yet endocrine responses vary widely. In a school-based pilot study (n = 11; aged 9–10 years), we examined whether the temporal structure of facilitator–child rhythmic interaction relates to pre–post changes in salivary oxytocin. Chest-mounted accelerometry (20 Hz) from the facilitator and each child during a 30-min drum circle was decomposed into a rhythm band (0.3–3 Hz) and a beat-related component. We estimated time-resolved directed coupling using transfer entropy (60-s windows, 5-s step) and computed directional asymmetry (ΔTE). Salivary oxytocin increased from pre to post (paired t-test, two-sided, p = 0.022), while cortisol showed no significant change. Individual oxytocin change was not strongly related to conventional summary indices of directional influence. Instead, oxytocin change was inversely associated with the longest sustained episode of significant unidirectional rhythmic influence (Spearman ρ = −0.72, p = 0.013). These exploratory findings suggest that prolonged unidirectional lock-in at the rhythmic timescale may be less conducive to oxytocin increases than dynamically shifting, bidirectional exchange. Larger preregistered studies are needed to determine whether temporal persistence of directional coupling provides a biologically relevant marker of engagement during group music-making.
Rosuvastatin Attenuates Pulmonary Damage in Rats with Cecal Ligation and Puncture-Induced Sepsis
In a rat study, these findings suggest that rosuvastatin may have therapeutic potential in the management of sepsis-associated lung injury, although further studies are required to confirm its clinical applicability.
Yıldız Sİ, Saydam F, Topçu A, Tümkaya L, Kutlu EY, Uydu HA.
Background: /Objectives: Sepsis is a life-threatening condition characterized by a dysregulated host immune response, frequently leading to multiple organ dysfunction, with the lungs being among the most severely affected organs. Oxidative stress, inflammation, apoptosis, and DNA damage play key roles in the pathogenesis of sepsis-induced acute lung injury (ALI). Beyond its lipid-lowering effects, rosuvastatin possesses anti-inflammatory and antioxidant properties that may confer protective effects in sepsis. This study aimed to evaluate the dose-dependent effect of rosuvastatin against pulmonary damage in an experimental model of sepsis induced by cecal ligation and puncture (CLP). Methods: Sprague–Dawley rats were randomly divided into six groups: Sham, Sham + rosuvastatin (10 mg/kg), Sham + rosuvastatin (20 mg/kg), CLP, CLP + rosuvastatin (10 mg/kg), and CLP + rosuvastatin (20 mg/kg). Rosuvastatin was administered via oral gavage before 4 hours the CLP procedure in the experimental groups. All rats were euthanized 16 hours after induction of CLP. Lung tissues were analyzed for biochemical markers, including malondialdehyde (MDA) and reduced glutathione (GSH), as well as histopathological changes and immunohistochemical expression of NF-κB/p65, caspase-3, and 8-OHdG. Results: CLP-induced sepsis significantly increased MDA levels while decreasing GSH levels, indicating enhanced oxidative stress. Rosuvastatin treatment significantly reversed these changes. Histopathological analysis revealed marked lung injury in the CLP group, including alveolar inflammation, interstitial inflammation, vascular congestion, and increased alveolar septal thickness, all of which were significantly reduced following rosuvastatin administration. Immunohistochemical findings demonstrated increased expression of NF-κB/p65, caspase-3, and 8-OHdG in the CLP group, whereas rosuvastatin significantly attenuated these expressions. No significant differences were observed between the two rosuvastatin doses. Conclusion: Rosuvastatin exerts significant protective effects against sepsis-induced lung injury by reducing oxidative stress, inflammation, apoptosis, and DNA damage. These findings suggest that rosuvastatin may have therapeutic potential in the management of sepsis-associated pulmonary injury, although further studies are required to confirm its clinical applicability.
Enhanced cardioprotective effects of resveratrol and liraglutide against isoproterenol-induced myocardial injury: role of oxidative stress, inflammation, and mitochondrial function
In a rat study, this combination may represent a promising therapeutic strategy for myocardial injury.
El-Deen AEN, Taha R, Esmail SFA, Sayed MH, Ahmed MZH, Elfiky MA, El-Rhman AAA, Farag OK, Mohammed MAA, Ghany AFA, Allah AG, Taha A.
Abstract Background: Myocardial infarction (MI) remains a leading cause of global mortality and is strongly associated with oxidative stress, mitochondrial dysfunction, and inflammatory responses that contribute to irreversible cardiac injury. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide, have demonstrated cardioprotective effects beyond glycemic control, while resveratrol, a natural polyphenol, exhibits potent antioxidant and mitochondrial-protective properties. However, the combined effects of these agents on mitochondrial function in myocardial injury have not been fully explored. Objective: This study aimed to evaluate the combined cardioprotective effects of resveratrol and a GLP-1 receptor agonist (liraglutide) against isoproterenol (ISO)-induced myocardial injury in rats, with particular emphasis on oxidative stress and mitochondrial dysfunction. Methods: Seventy adult male albino rats were randomly allocated into five groups: Control, ISO (100 mg/kg, s.c., for two consecutive days), Resveratrol + ISO (20 mg/kg/day, orally for 28 days), GLP-1 RA + ISO (liraglutide 0.2 mg/kg/day, s.c., for 10 days), and Resveratrol + GLP-1 RA + ISO. ISO was administered on days 27 and 28. Cardiac injury was assessed using serum biomarkers (cTnI, CK-MB, LDH), oxidative stress markers (MDA, SOD, GSH), inflammatory cytokines (TNF-α, IL-6), and mitochondrial function parameters, including mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) generation. Histopathological evaluation of cardiac tissue was also performed. Results: ISO administration significantly increased cardiac injury markers, lipid peroxidation, and pro-inflammatory cytokines, while reducing antioxidant defenses and impairing mitochondrial function (p Conclusion: The combined administration of resveratrol and liraglutide provides enhanced cardioprotection against ISO-induced myocardial injury, likely through complementary effects on oxidative stress, inflammation, and mitochondrial function. While interaction analysis suggests a greater-than-additive effect, further studies using dedicated synergy models and molecular validation are required. This combination may represent a promising therapeutic strategy for myocardial injury.
Semaglutide cardiovascular outcomes align more closely with attained dose than achieved weight loss
In a case report, to reduced confounding, we performed propensity-matched comparisons during the landmark period, in which semaglutide was associated with lower rates of cardiovascular events than metformin, DPP-4 inhibitors, and SGLT2 inhibitors; however, these findings should be interpreted as associative and remain susceptible to treatment selection bias.
Murugadoss K, Venkatakrishnan AJ, Gregg C, Soundararajan V.
Abstract Semaglutide is often optimized for weight loss, but whether longer-term cardiovascular benefit tracks achieved weight loss or therapeutic exposure levels remains unclear. We conducted a retrospective observational study using a federated, deidentified U.S. electronic health record network and applied multimodal AI-based methods to analyze 47,199 patients with baseline cardiovascular disease. We quantified dose escalation and weight change during the 0–2-year period after semaglutide initiation (landmark period) and assessed cardiovascular outcomes during the 2–4-year period (post-landmark). To mitigate confounding, we performed propensity-matched comparisons during the landmark period, in which semaglutide was associated with lower rates of cardiovascular events than metformin, DPP-4 inhibitors, and SGLT2 inhibitors; however, these findings should be interpreted as associative and remain susceptible to treatment selection bias. Higher maximum semaglutide dose was associated with greater weight loss during the landmark period (3.15% additional weight loss per 1 mg increase; r = − 0.97, P