Peptide Research Database
Access 6,188 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.
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.
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).
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.
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.
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.
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.
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.
Ectopic ACTH-dependent Cushing syndrome in 3 hospitalized patients: lessons learned from management with osilodrostat.
In a clinical study, our experience suggests that rapid initiation and titration of osilodrostat effectively treats hypercortisolism and improves outcomes.
Ruggles H, Yang E, Mohan N, Espinosa LB, Harris E, Jones M
Severe Cushing syndrome (CS) is a rare diagnosis with high mortality, which limits the ability of endocrinologists to gain experience delivering care. Here we describe our experience treating 3 cases of ectopic ACTH-dependent CS presenting in a single year. The initial diagnosis of each case was made during hospitalization resulting from complications of CS, implicating severe disease and delayed diagnosis. Our experience suggests that rapid initiation and titration of osilodrostat effectively treats hypercortisolism and improves outcomes.
Simplified definition and imaging-based stratification of at-risk MASH using magnetic resonance elastography.
In a case report, these findings support the use of MRE to guide resmetirom and semaglutide eligibility and improve access to emerging therapies. Aimed to standardize the definition of at-risk MASH and propose optimized MRE-based liver stiffness (LS-MRE) cutoffs to improve noninvasive risk stratification and better guide pharmacotherapy.
Li J, Wu H, Glaser KJ, Ou FS, Manduca A, Venkatesh SK, Sirlin C, Loomba R, Shah VH, Ehman RL, Allen AM, Yin M
Accurate identification of patients with metabolic dysfunction-associated steatohepatitis (MASH) at risk of disease progression (at-risk MASH) is critical for guiding resmetirom and semaglutide therapy. Inconsistent definitions of at-risk MASH complicate clinical risk classification and comparisons across studies. This study aimed to standardize the definition of at-risk MASH and propose optimized MRE-based liver stiffness (LS-MRE) cutoffs to improve noninvasive risk stratification and better guide pharmacotherapy. In this prospective study, 413 patients with suspected or diagnosed MASLD from two medical centers underwent liver biopsy and MRE. A simplified definition of at-risk MASH (MASH with fibrosis stage≥2) identified a broader group of patients requiring clinical attention than a stricter definition requiring NAFLD Activity Score≥4 with ≥1 point in steatosis, inflammation, and ballooning (n=122 vs. 77). LS-MRE alone showed the highest diagnostic accuracy for identifying at-risk MASH using the simplified definition (AUC 0.91 [0.87, 0.95]) and cirrhosis (AUC 0.93 [0.88, 0.99]), compared with FIB-4 and individual laboratory parameters (AST, ALT, and platelet count) (p<0.01 for all, paired DeLong tests). Optimized LS-MRE cutoffs (2.8-6.4 kPa) captured 25 additional biopsy-proven pharmacotherapy candidates (28% of all eligible patients) compared to AASLD guidelines-recommended cutoffs (3.1-4.4 kPa), improving sensitivity (80% vs. 50%) with acceptable specificity (73% vs. 88%). A simplified definition of at-risk MASH enables broader identification of treatment candidates. LS-MRE demonstrates excellent diagnostic performance and improves noninvasive risk stratification when paired with optimized cutoffs. These findings support the use of MRE to guide resmetirom and semaglutide eligibility and improve access to emerging therapies.