Peptide Research Database
Access 4,900 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.
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.
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.
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.
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).
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.
Glucagon-Like Peptide-1 Receptor Agonists in the Real World: Are Clinical Trials Reproducible? A Spanish Pilot Study
In a case report, these findings support the need for individualized treatment strategies in obesity care.
Vergniory-Trueba O, Treceño-Lobato C.
Introduction: Obesity is a chronic, multifactorial disease associated with significant metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor ago-nists (GLP-1RAs) have emerged as effective pharmacological options for weight man-agement, demonstrating clinically relevant weight loss in controlled trials. However, real-world evidence is essential to assess their effectiveness and safety under routine clinical conditions and to verify if trial results are reproducible in diverse populations. Objective: To evaluate the effectiveness and safety of GLP-1RAs in terms of weight loss in real-world clinical practice and to compare outcomes among different available agents, focusing on their impact on obesity management. Method: A cross-sectional, observational pilot study was conducted in Spain. Adult patients receiving GLP-1RAs for at least four weeks were included. Data collected included sociodemographic vari-ables, treatment characteristics, anthropometric measurements, and adverse effects. Weight loss outcomes were analyzed using descriptive statistics, ANOVA for in-ter-drug comparisons, and multivariate ANCOVA to adjust for confounders. This pilot study also validated the protocol for a subsequent nationwide multicenter study. Re-sults: A total of 32 patients (62.5% women; mean age 58.2 years) were analyzed. Mean weight loss was 2.97 kg (3.17%). Significant differences between drugs were observed (p = 0.005), with semaglutide 2.4 mg (Wegovy) showing the greatest reduction (11.0 kg). Patients without diabetes achieved significantly greater weight loss than those with diabetes (5.0 vs. 0.8 kg; p = 0.021). Treatments were well tolerated, with 53.1% re-porting no adverse effects; most side effects were mild gastrointestinal symptoms. Conclusions: GLP-1RAs are effective and well-tolerated for obesity treatment in re-al-world clinical practice, although weight loss is more modest than in pivotal clinical trials. Differences between agents persist after adjustment, with specific formulations like semaglutide 2.4 mg showing superior effectiveness. These findings support the need for individualized treatment strategies in obesity care. This pilot study success-fully validated the methodology for an ongoing nationwide investigation
Glucagon-Like Peptide-1 Receptor Agonists in Chronic Migraine: A Convergent Disease-Modification Hypothesis
In a clinical study, a biochemical scheiding between exendin-based agonists (exenatide, lixisenatide) and human GLP-1 analogues (semaglutide, liraglutide, dulaglutide) generates a falsifiable sub-hypothesis on peripheral TRPV1 inhibition that is testable retrospectively on data that already exist.
Sulter GA.
Chronic migraine is increasingly understood as a network-level disorder in which trigeminovascular nociception is sustained by metabolic, inflammatory, and macro-network dysfunction rather than by an isolated headache mechanism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, engage receptors expressed in choroid plexus, cortex, hippocampus, thalamus, and hypothalamus. Evidence converges on four mechanistic intersections between GLP-1 signalling and the chronic-migraine cascade: restoration of cerebral insulin signalling and cortical energy supply; modulation of cerebrospinal-fluid secretion and intracranial pressure with downstream relevance for glymphatic dynamics (most clearly validated in idiopathic intracranial hypertension, with explicit caveats for normotensive migraine); suppression of microglial activation in pain-relevant circuits (established preclinically, with one pilot human imaging study); and direct trigeminal-nociceptor effects via TRPV1 inhibition demonstrated for exendin-derived peptides. A 2026 real-world cohort of approximately 11,000 chronic-migraine adults provides a preliminary clinical signal. We propose, and operationalise as falsifiable, the hypothesis that GLP-1RAs are disease-modifying rather than purely symptomatic in chronic migraine, and we describe a placebo-controlled trial with parallel multiple mediation analysis on weight change AND HOMA-IR/TyG delta that can refute the claim within five years. A biochemical scheiding between exendin-based agonists (exenatide, lixisenatide) and human GLP-1 analogues (semaglutide, liraglutide, dulaglutide) generates a falsifiable sub-hypothesis on peripheral TRPV1 inhibition that is testable retrospectively on data that already exist.
The Nonlinear Relationship Between Maternal Temperature Variation and Total Duration of Labor: A Cross-Sectional Study of 6,654 Parturients with Epidural Analgesia
This study found below this threshold, each 0.1°C increment in temperature variation was notably associated with prolonged labor (β = 17.4 min, 95% CI: 14.6 to 20.3, P. Aimed to investigate the association between maternal temperature change and total duration of labor in parturients receiving epidural analgesia.
Wu Z, Yu H, Ke W, Zhou J, Shi J, Lai Y, Chen W, Wu Z, Zhao Y.
Abstract Background Epidural analgesia is associated with maternal hyperthermia during labor, but the relationship between temperature variation and labor progression remains unclear. This study aimed to investigate the association between maternal temperature change and total duration of labor in parturients receiving epidural analgesia. Methods This cross-sectional study included 6,654 parturients who received epidural analgesia for vaginal delivery at Maternity&Child Healthcare Hospital of Longgang District, Shenzhen City in 2024. Generalized additive models and two-piecewise linear regression were employed to examine the dose-response relationship and threshold effects. Subgroup analyses were performed by parity and oxytocin use. Results A nonlinear, inverted U-shaped relationship was identified between temperature variation and total labor duration, with an inflection point at 1.2°C. Below this threshold, each 0.1°C increment in temperature variation was significantly associated with prolonged labor (β = 17.4 min, 95% CI: 14.6 to 20.3, P
Endogenous Incretin Secretagogue Compositions as a Mechanistic Class Versus Pharmacological Incretin Receptor Agonists for Weight Reduction in Overweight Adults: A Real-World Observational Cohort Analysis of a Nutraceutical Composition (Trimsulin) and Comparison with Published Outcomes for Semaglutide and Tirzepatide
In a randomized trial, [11–14] Beyond supplement formats, investigation of BSM-framework ingredient systems in functional food and food-additive delivery formats represents a translational research direction of broader public health relevance, given the potential for population-scale access that food-category routes offer relative to pharmaceutical channels.
Kaufman RC.
Abstract Background: Pharmacological glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists such as tirzepatide produce clinically meaningful weight reduction in adults with overweight or obesity. However, gastrointestinal and serious adverse events affect a substantial proportion of treated patients, contributing to discontinuation and limiting long-term adherence. Nutraceutical compositions designed to stimulate endogenous GLP-1 and GIP secretion may offer a tolerability advantage. Objective: To describe weight change and adverse event rates in a real-world cohort of overweight adults using a nutraceutical endogenous incretin secretagogue composition (Trimsulin Weight Loss Program) and to compare these outcomes with publicly available outcome data for semaglutide and tirzepatide. Methods: Observational cohort analysis of 503 overweight adults enrolled in the Trimsulin Weight Loss Program, comprising two nutraceutical products (Control, a powdered drink mix; Thermo, a capsule formulation) taken twice daily before meals, plus a structured dietary protocol and a moderate-exercise recommendation. Body weight, BMI, and participant-reported adverse events were tracked at 12 weeks and 24 weeks. Comparative weight-loss outcomes for semaglutide and tirzepatide were drawn from the on-treatment estimand of the published Truveta-derived real-world cohort analysis by Rodriguez et al. (n = 18,386; mean baseline BMI 39.0). Comparative adverse event rates were drawn from a separate body of clinical trial and pharmacovigilance evidence. Outcomes are reported descriptively; no inferential statistical testing was performed between cohorts. Results: Of more than 1,000 enrolled program participants, 503 completed six months of program participation with protocol-conformant follow-up measurements and constitute the analysis cohort. Mean baseline weight was 201.2 lb (range 130–360); mean BMI was 27.5 (range 20.0–50.1). At 3 months, mean weight reduction was 7.3% in the Trimsulin cohort, compared with 3.6% (semaglutide) and 5.9% (tirzepatide) reported in published comparator data. At 6 months, mean reductions were 14.1%, 5.8%, and 10.1%, respectively. Any adverse event was reported by 4.8% of Trimsulin participants, compared with 89.7% (semaglutide) and 81.0% (tirzepatide) in published trial cohorts. No serious adverse events were reported in the Trimsulin cohort, compared with approximately 3.0% for semaglutide and 5–7% for tirzepatide. These hypothesis-generating findings support further controlled investigation of endogenous incretin secretagogue compositions as a class. The present cohort study evaluated one licensed implementation of the BSM platform framework. Future research directions of highest priority include prospective randomized controlled trials of BSM-framework compositions — including next-generation formulations incorporating more advanced ingredient systems and delivery architectures — compared against placebo and against active pharmacological incretin comparators. Secondary endpoints of particular mechanistic value include changes in plasma active GLP-1 and GIP concentrations, DPP-4 activity, fasting and post-prandial glycemic response, UCP-1 induction, and patient-reported tolerability. A factorial design apportioning the contribution of the BSM supplement components versus the dietary and behavioral program elements would clarify the mechanistic contribution of each. Adjunctive use of BSM-framework compositions in patients who discontinue pharmacological incretin therapy due to intolerance represents a clinically meaningful research direction, given the established real-world discontinuation burden of pharmacological GLP-1 receptor agonists. [11–14] Beyond supplement formats, investigation of BSM-framework ingredient systems in functional food and food-additive delivery formats represents a translational research direction of broader public health relevance, given the potential for population-scale access that food-category routes offer relative to pharmaceutical channels.
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.