Peptide Research Database

Access 6,575 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.

Animal Study
Notable
PMID: 42627259
2026 Dec 31

Rethinking dog stress behaviours: contextual and physiological insights from the attachment framework.

In an animal study, our findings suggest that the observed behaviours were not expressed linearly in relation to expected stress levels across the SSP episodes. Using the Strange Situation Procedure (SSP) as a social-stress paradigm, we evaluated contextual correlates of dog behaviours to explore their validity as stress indicators.

Riggio G, Borrelli C, Atilgan D, Russo G, Diverio S, Mariti C

While dogs' behavioural indicators of psychological stress are widely used, their function as reliable stress markers remains debated. Using the Strange Situation Procedure (SSP) as a social-stress paradigm, we evaluated contextual correlates of dog behaviours to explore their validity as stress indicators. In 64 dogs, behaviours commonly used as stress markers were video-coded and analysed via GLMMs to investigate differences across test episodes and attachment styles (secure, anxious, avoidant), while salivary cortisol, oxytocin, and rectal temperature provided a physiological framework. Episode had significant effects on shaking (p < 0.05), lip-licking (p < 0.001), paw-lifting (p < 0.001), whining (p < 0.001), head-turning (p < 0.001), sniffing the door (p < 0.001), and locomotion (p < 0.001), while attachment style significantly affected head-turning only (p = 0.004). Our findings suggest that the observed behaviours were not expressed linearly in relation to expected stress levels across the SSP episodes. This lack of linearity, combined with the divergent physiological correlates found across attachment groups-for instance, oxytocin correlated positively with lip-licking in securely attached dogs (p < 0.05), but negatively in anxious ones (p < 0.05) -, suggests that these behaviours do not function as simple stress indicators. Rather, their meaning appears to be contingent upon the individual's internal state and the socio-environmental context. We discuss our results in light of an alternative semiotic interpretative framework.

The veterinary quarterly
Clinical Trial
Highly Cited
PMID: 42610532
2026 Dec 31

Hunger pain and its reduction; qualitative insight from people with schizophrenia on semaglutide.

In a clinical study, it is relevant to assess patients' eating problems prior to semaglutide treatment. As part of the RCT "Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes, HISTORI", the present study investigates experiences of hunger and eating habits in people using antipsychotics during semaglutide treatment.

Rasmussen BS, Simonÿ C, Poulsen ML, Uhrenholt NG, Lundberg B, Rønne ST, Uhrenholt PG, Gæde PH, Arnfred SM

It is often reported that people with schizophrenia experience weight gain and disordered eating, partly due to antipsychotics. As part of the RCT "Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes, HISTORI", the present study investigates experiences of hunger and eating habits in people using antipsychotics during semaglutide treatment. Eleven semi-structured interviews were conducted 4 months to 1,5 years after treatment completion. Six women and 5 men were interviewed. The interviews were analysed using Braun & Clarke's reflexive thematic analysis. Three themes were identified; "Hunger pain induced by antipsychotic medicine", "Positive and negative experiences of reduced hunger", and "Eating habits and what influences them". The term "Hunger pain" was applied. It defines an excruciating combination of feeling extremely hungry, never achieving satiety, and relentless preoccupation with thoughts about food. The analysis suggested a focus on the patients' coping styles. The hunger pain, probably induced by antipsychotics, seemed to reinforce maladaptive coping styles. The relief from hunger pain due to semaglutide was in most cases a liberation. Yet, it is important also to pay attention to the negative effects of reduced hunger. It is relevant to assess patients' eating problems prior to semaglutide treatment.

International journal of qualitative studies on health and well-being
Other
PMID: 42578506
2026 Dec

Design, synthesis, and stability evaluation of semaglutide-derived lactam-stapled peptide scaffolds for GLP-1R targeting.

This study found collectively, these results define a practical strategy for constructing stabilised semaglutide-derived peptide scaffolds and provide a basis for subsequent functional optimisation of GLP-1R-targeting peptides.

Liu T, Ren X, Li Y, Wang J, Chen J, Lin R, Zhang J

Glucagon-like peptide-1 receptor (GLP-1R) ligands including semaglutide play an important role in drug discovery. Herein, a short semaglutide-derived GLP-1R-engaging segment was used as the basis for scaffold construction, and conformational restabilisation was introduced through lactam stapling and bulky aromatic non-natural amino acid substitution. A total of 108 stapled peptide candidates were designed by structure-guided modelling and virtual screening. Among them, 35 peptides were synthesised and characterised. Most stapled analogues showed improved serum and proteolytic stability relative to semaglutide, and 11CP-17B, 11CP-17N, and 11CP-19N showed the most favourable stability profiles. Molecular dynamics simulations and MM-GBSA analysis were consistent with receptor-compatible poses and favourable predicted interaction patterns for these representative analogues. Collectively, these results define a practical strategy for constructing stabilised semaglutide-derived peptide scaffolds and provide a basis for subsequent functional optimisation of GLP-1R-targeting peptides.

Journal of enzyme inhibition and medicinal chemistry
Clinical Trial
Notable
PMID: 42021523
2026 Dec

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.

Journal of medical economics
Review
Notable
PMID: 41999297
2026 Dec

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.

Annals of medicine
Animal Study
Notable
PMID: 42494251
2026 Dec

Soy protein alleviates DKD by restraining inflammation via the MAPKs/PPAR-γ signaling pathway.

In a mouse study, soy protein alleviates DKD via genistein, which inhibits p38 MAPK and activates PPAR-γ to reduce inflammation/cell damage from free radicals, supporting soy-based DKD interventions. Explored if soy protein alleviates DKD via the MAPKs/PPAR-γ pathway.

Zhang Y, Xie J, Wang M

Diabetic Kidney Disease (DKD), a leading cause of kidney failure driven by chronic inflammation and dysregulated signaling, lacks effective therapies. This study explored if soy protein alleviates DKD via the MAPKs/PPAR-γ pathway. Bioinformatics on GEO datasets (GSE154881, GSE139317) identified differentially expressed genes (DEGs): GSE154881 (peripheral blood) had 580 DEGs enriched in inflammation/MAPK signaling; GSE139317 (kidney tissues) had 2830 DEGs enriched in fatty acid metabolism/PPAR signaling, suggesting MAPK-PPAR-γ crosstalk. Although soy isoflavones have been reported to modulate MAPK or PPAR-γ signaling in other diseases, whether soy protein affects this pathway crosstalk in DKD remains unknown. Based on the bioinformatic prediction, we hypothesized that soy protein ameliorates DKD by targeting the MAPKs/PPAR-γ axis. In streptozotocin-induced DKD mice, soy protein (200-800mg/kg) dose-dependently reduced serum creatinine, blood urea nitrogen, blood glucose, tubular injury, kidney pro-inflammatory cytokines (MCP-1, IL-6, TNF-α), and reversed weight loss. In high glucose-stimulated HK-2 cells, genistein (soy isoflavone, 20-100μM) dose-dependently restored viability, reduced MDA (oxidative stress), increased GSH (antioxidant), and lowered cytokines. p38 MAPK agonist (diprovocim) or PPAR-γ antagonist (GW9662) abolished these effects. Soy protein alleviates DKD via genistein, which inhibits p38 MAPK and activates PPAR-γ to reduce inflammation/oxidative stress, supporting soy-based DKD interventions.

Renal failure
Other
PMID: 42639925
2026 Dec

Clinical practice patterns and unmet needs in the use of GLP-1 receptor agonists in sleep medicine: A pan-European survey performed in the European sleep apnoea database network.

In a clinical study, harmonised guidance and coordinated multidisciplinary care are urgently needed.

Testelmans D, Bonsignore MR, Pataka A, Fanfulla F, Ryan S, Lombardi C, Randerath W, Grote L, Kalkanis A

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 agonists have demonstrated weight loss benefits and reductions in obstructive sleep apnoea (OSA) severity. Following recent regulatory approval of tirzepatide for OSA with obesity, their integration into sleep medicine is accelerating. However, real-world clinical practice remains undefined. The European Sleep Apnoea Database (ESADA) network conducted a multinational online survey across 24 centres in 14 European countries to evaluate current practice patterns regarding GLP-1RA use in patients with obesity and suspected or established OSA. Forty-two percent of centres reported that GLP-1RA therapy could be initiated by sleep physicians within the sleep clinic. Indications were consistent, primarily targeting moderate-to-severe obesity with metabolic comorbidities. Most clinicians continued to recommend diagnostic sleep studies in symptomatic (92%) and asymptomatic (81%) patients recently started on GLP-1RAs. A weight loss threshold > 10% was considered clinically meaningful for OSA reassessment by 61% of centres. Despite anticipated reductions in OSA severity, proactive positive airway pressure (PAP) re-titration or withdrawal was uncommon (14%). Monitoring focused on weight trajectory, symptoms, and PAP telemonitoring. Structured interdisciplinary pathways were largely absent. GLP-1RAs are increasingly incorporated into European sleep practice; however, substantial variability exists in diagnostic timing, PAP management, and follow-up strategies. Harmonised guidance and coordinated multidisciplinary care are urgently needed.

Clinical Trial
Highly Cited
PMID: 42480078
2026 Dec

Effect of oral calcium carbonate on uterine contractility: a pilot randomised controlled trial.

In a clinical study, these findings likely reflect the limited physiologic effect of oral calcium on serum calcium levels.

Bui TM, Nelson M, Rehman R, Stowe Ii RJ, Roloff KA, Valenzuela GJ

Ineffective uterine contractions contribute to labour dystocia and are a leading indication for primary caesarean delivery. Although oxytocin is the standard therapy for augmentation, prolonged exposure may result in receptor desensitisation and reduced effectiveness. Calcium is essential for myometrial contraction; however, systemic calcium homeostasis is tightly regulated, and it is unclear whether oral calcium supplementation can meaningfully influence uterine activity. This study aimed to evaluate the effect of oral calcium carbonate on uterine contractility. We conducted a single-centre randomised controlled pilot trial at a tertiary care teaching hospital (ClinicalTrials.gov: NCT07056062). Term patients with singleton foetus in cephalic presentation and an intrauterine pressure catheter in place were randomised 1:1 to receive a single 2,000 mg oral dose of calcium carbonate or no intervention. Uterine activity was measured using Montevideo units (MVUs) at baseline and at 30-minute intervals for two hours. Secondary outcomes included contraction frequency, peak contraction pressure, labour duration, mode of delivery, oxytocin dose, and postpartum haemorrhage. Oxytocin infusion rates were held constant during the observation period. Eighty-nine patients were analysed (45 control; 44 intervention) with similar baseline characteristics. No statistically significant difference in baseline MVUs was observed between groups (p = 0.1825). Although absolute MVUs were higher in the intervention group at 30 minutes (p = 0.0500), this difference was not sustained at subsequent time points and was absent in change-from-baseline analyses, suggesting no clinically meaningful treatment effect. No statistically significant differences were identified in secondary outcomes. Oral calcium carbonate did not result in a statistically significant improvement in uterine contractility or clinical outcomes. These findings likely reflect the limited physiologic effect of oral calcium on serum calcium levels. Oral calcium carbonate appears unlikely to be an effective intervention for labour augmentation; future research should focus on strategies with more controllable mechanisms.

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology
Animal Study
Notable
PMID: 41991506
2026 Dec

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.

Renal failure
Case Report
Notable
PMID: 42495930
2026 Dec

Comparison of lifestyle, surgery, and semaglutide for weight management in endometrial cancer: a prospective observational study.

In a case report, integrated lifestyle support may be a useful medium-term strategy for patients seeking fertility preservation.

Wei Y, Gong Y, Gong J, Zeng H, Zhong Z, Xiong Y, Li X

To compare sleeve gastrectomy, semaglutide therapy, and the Diet, Exercise, Accompany and Refresh (DEAR) weight management programme for weight control, metabolic improvement, and oncological outcomes in patients with endometrial cancer receiving fertility-sparing treatment. In this prospective observational study, 53 patients received sleeve gastrectomy (n = 10), semaglutide therapy (n = 23), or the DEAR programme (n = 20) after multidisciplinary assessment and shared decision-making. Anthropometric and metabolic measures and tumour response were assessed over two years. At 1 year, all groups lost weight; the sleeve gastrectomy group had the largest body mass index reduction compared with the semaglutide group (difference = 4.04 kg/m2, p < 0.05) and the DEAR group (difference = 2.12 kg/m2, p < 0.05). By 2 years, weight regain was less frequent in the DEAR group (14.3%) than in the semaglutide (55.6%) and sleeve gastrectomy (66.7%) groups (p = 0.037). The DEAR group showed more stable metabolic improvements and the highest complete tumour remission rate (85.0%), followed by the semaglutide group (73.9%) and the sleeve gastrectomy group (60.0%). Sleeve gastrectomy produced rapid short-term weight loss, whereas the DEAR programme showed better medium-term weight maintenance, metabolic stability, and tumour response. Integrated lifestyle support may be a useful medium-term strategy for patients seeking fertility preservation.

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology