Peptide Research Database
Access 5,476 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.
The Combination of Oxytocin with Mindfulness-Based Group Therapy Reduces Negative Symptoms in Schizophrenia Spectrum Disorders: A Triple-Blind, Placebo-Controlled, Randomized, Controlled Clinical Pilot Trial (OXYMIND)
In a randomized trial, conclusions These findings suggest, oxytocin combined with MBGT may improve negative symptoms in SSD and support further large-scale trials.
Zierhut M, Alt M, Hahne IM, Bergmann N, Opper F, Braun K, Braun A, Kraft J, Ta TMT, Ripke S, Bajbouj M, Hahn E, Boege K.
Background Negative symptoms in schizophrenia spectrum disorders (SSD) remain insufficiently treated and require novel therapeutic approaches. Oxytocin may improve negative symptoms, although its effects appear highly context-dependent according to the social salience hypothesis. We conducted a randomized, triple-blind, placebo-controlled pilot study combining intranasal oxytocin with mindfulness-based group therapy (MBGT), hypothesizing that the positive social context of MBGT would enhance oxytocin-related effects. Methods 47 participants with SSD (34% female) were randomized to receive either 24 IU oxytocin (MBGT+OXT; n = 26) or placebo (MBGT+PLA; n = 21) before four MBGT sessions. Primary outcome was negative symptoms assessed with the Positive and Negative Syndrome Scale negative subscale (PANSS-N) at post-intervention and 4-week follow-up. Secondary outcomes included the Brief Negative Symptom Scale (BNSS), Self-Evaluation of Negative Symptoms Scale (SNS), and additional clinical measures. Linear mixed models estimated within- and between-group effects. Results Overall dropout rate was 14.89%, with one dropout potentially treatment-related. Blinding was successful. Participants completed 95.63% of sessions. Only the MBGT+OXT group showed significant improvements in PANSS-N from baseline to post-intervention (d = -0.74) and follow-up (d = -0.77), with a small between-group effect at follow-up (d = 0.39). BNSS total improved significantly only in the MBGT+OXT group from baseline to post-intervention (d = -0.88) and follow-up (d = -0.91), with between-group effects favoring MBGT+OXT at follow-up (d = -0.38). No serious adverse events occurred. Conclusions These findings suggest, oxytocin combined with MBGT may improve negative symptoms in SSD and support further large-scale trials. Clinical Trials Registration: https://clinicaltrials.gov/study/ NCT06136390 , Registration number: NCT06136390
Oxytocin receptor dysfunction during neurodevelopment programs lasting pain hypersensitivity and sex-specific cognitive deficits
In a rat study, these findings demonstrate that developmental OTR dysfunction likely contributes to nociceptive and cognitive consequences of ELS, while anxiety-like phenotypes probably involve additional mechanisms. Here, we investigated whether neonatal OTR blockade alone could recapitulate key features of the NMS phenotype.
Illouz H, Tanche E, Schaack O, Lelievre V, Poisbeau P.
Early life stress (ELS), modeled in rodents through neonatal maternal separation (NMS), induces lasting behavioral and molecular alterations including pain hypersensitivity, anxiety-like behaviors, and cognitive deficits. While NMS disrupts the oxytocinergic system, the specific contribution of oxytocin receptor (OTR) dysfunction during critical neurodevelopmental periods remains unclear. Here, we investigated whether neonatal OTR blockade alone could recapitulate key features of the NMS phenotype. Control rats received daily injections of the selective OTR antagonist d(CH2)5-Tyr(Me)-[Orn8]-vasotocin (dOVT) during postnatal days 2-12, matching the NMS period. At adulthood, behavioral assessments revealed that control+dOVT animals exhibited mechanical and cold thermal hypersensitivity similar to NMS rats, though hot thermal sensitivity was unaffected. Anxiety-like behaviors observed in NMS animals were not reproduced by dOVT treatment. Notably, sex-specific spatial memory deficits emerged: male NMS and female control+dOVT rats showed impaired object location recognition, while females and males in their respective opposite groups remained unaffected. Molecular analyses of spinal cord tissue revealed significant downregulation of GAD65, BDNF, and CD11b in control+dOVT animals. Chloride cotransporters NKCC1 and KCC2 exhibited sexual dimorphism with opposite changes in NMS males versus females and different responses to dOVT. These expressions yet converged on an elevated NKCC1/KCC2 ratio in both sexes, indicating compromised chloride homeostasis despite sex-divergent molecular pathways. These findings demonstrate that developmental OTR dysfunction likely contributes to nociceptive and cognitive consequences of ELS, while anxiety-like phenotypes probably involve additional mechanisms. This work highlights OTR as a critical mediator of neurodevelopmental programming and a potential therapeutic target for mitigating ELS-related disorders.
The insertion of Neomycin cassette impairs maternal and social behaviors in Arc/Arg3.1 knock-out mice
In a mouse study, together, our findings demonstrate that the Neo cassette influence behavioral phenotypes, particularly social and maternal behavior in Arc/Arg3.1 KO mice, highlighting the need to carefully re-evaluate conclusions drawn from animal models retaining the Neo cassette in neuroscience research. Identified severe impairments in maternal behavior in Neo +, but not Neo − Arc/Arg3.1 KO dams.
Pellissier L, Dudas A, CAIRE E, KUKU AHA, MARCHAND O, AZZOPARDI N, ELSEEDY H, JUGNARAIN V, VACHER H, Piégu B, ANNAMNEEDI A, Pecnard E, BRUNEAU G, Drobecq L, Trouillet A, YVINEC R, Lefort G, Crepieux P, Sirigu A, Kuhl D, Ohana O, Chamero P.
Abstract The Neomycin resistance cassette (Neo + ) is commonly inserted in the genome of mice to generate knock-out (KO) models. The effect of gene deletion on social behaviors in mice is inconsistent across studies using Neo + and Neo − lines, particularly Arc/Arg3.1 KO models. In this study, we identified severe impairments in maternal behavior in Neo + , but not Neo − Arc/Arg3.1 KO dams. These deficits were associated with reduced sociability and abnormal social information processing in Neo + Arc/Arg3.1 KO dams, and were further exacerbated by impaired social communication in their pups. Mechanistically, although the Neo cassette product was not cytotoxic, its presence altered ERK signaling, gene expression profile, and the oxytocin system. However, oxytocin administration failed to rescue social deficits in Neo + Arc/Arg3.1 KO animals. Notably, early-life social enrichment improved social interaction with familiar conspecifics, but did not restore responses to unfamiliar animals or maternal behavior. Together, our findings demonstrate that the Neo cassette influence behavioral phenotypes, particularly social and maternal behavior in Arc/Arg3.1 KO mice, highlighting the need to carefully re-evaluate conclusions drawn from animal models retaining the Neo cassette in neuroscience research.
Plasma oxytocin measured by LC–MS/MS varies with life stage, sex, and obesity in mice
In a mouse study, a precise understanding of Oxt regulation in different conditions, backed by reliable methodologies, is indispensable for the rational development of effective treatments for obesity and related endocrine diseases. Objective Oxytocin (Oxt) assessment in plasma is challenging, and available data are contradictory.
Colleluori G, Galli C, Moretti S, Di Bona S, Severi I, Perugini J, Scopini E, Grandin G, Cruciani G, Giordano A.
Objective Oxytocin (Oxt) assessment in plasma is challenging, and available data are contradictory. We aimed to assess circulating Oxt in mice by a validated nano-liquid chromatography/mass-spectrometry (nLC-MS/MS) protocol, combined with Oxt hypothalamic expression in different sex, life stages, and in diet-induced obesity. Methods We assessed plasma Oxt by nLC-MS/MS, Oxt hypothalamic expression by qPCR, and Oxt-immunoreactive neuron and fiber densities by immunohistochemistry and morphometric analyses in C57BL/6 mice at 21 and 60 days of life (p21 and p60, respectively). Mice in normo-fed condition and following 12 weeks of high-fat diet (HFD) were studied alongside food intake and hypothalamic expression of its regulators. Results Circulating Oxt does not vary based on sex at p21 and p60 but increases with aging. While hypothalamic Oxt mRNA expression followed the same trend across both sexes, Oxt neuron and fiber densities exhibited a similar trend only in females. Plasma vasopressin (Avp) followed Oxt trend in females but was opposite in males and was not mirrored by Avp mRNA hypothalamic expression. HFD-fed females were more resistant to weight gain compared to males and displayed higher Oxt plasma levels and hypothalamic expression. Sex dimorphism in food intake and hypothalamic expression of Avp and of key anorexigenic and orexigenic neuropeptides was detected. Conclusions Oxt plasma levels are higher in adulthood compared to weaning in mice of both sexes who displayed similar concentrations. Oxt plasma levels are mirrored by Oxt hypothalamic expression. In obesity, females display a lower increase in body weight but higher Oxt plasma levels than males. Significance This study delineates the pattern of Oxt plasma levels across various age, sex and in obesity in mice. We overcome some limitations of previous research, which were often confounded by numerous factors, by reliably measuring circulating Oxt and integrating this with parallel analyses of Oxt gene expression, and Oxt neuron and immunoreactive fiber densities. Critically, this is among the few studies to employ LC-MS/MS specifically in mice. This novel, integrated perspective is relevant given the compelling evidence for Oxt’s role as an anti-obesity agent and its potential as a therapeutic target. A precise understanding of Oxt regulation in different conditions, backed by reliable methodologies, is indispensable for the rational development of effective treatments for obesity and related endocrine diseases.
Beyond Appetite: An MBM-Based Hypothesis for Dual-Action Anti-Obesity Pharmacotherapy Targeting Both Sides of the Mass Balance Equation
In a clinical trial, this MBM-based rational polypharmacy represents a paradigm shift from viewing obesity as a disorder of energy surplus to treating it as a disorder of mass flow dysregulation.
Manninen AH.
Anti-obesity pharmacotherapy has been transformed by potent GLP-1 and dual GIP/GLP-1 receptor agonists. Semaglutide and tirzepatide produce weight losses of 15–25%, magnitudes previously achievable only through bariatric surgery. Nevertheless, both agents encounter a consistent therapeutic plateau: after initial rapid weight reduction, loss progressively slows and eventually stabilizes despite ongoing treatment. The conventional energy balance model (EBM) attributes this plateau to poorly defined "compensatory metabolic adaptations" but provides no principled mechanistic explanation. In contrast, the mass balance model (MBM) frames the plateau as a predictable physical consequence of one-sided intervention. Current therapies reduce only net mass inflow (NMI) while allowing net mass outflow (NMO) to decline through two mechanisms: passive reduction driven by Torricelli's Law as body mass decreases, and active down-regulation of the mass clearance coefficient k. I hypothesize that combining an NMI-reducing agent (e.g., a GLP-1 or GIP/GLP-1 receptor agonist) with an NMO-stabilizing or NMO-enhancing agent will achieve greater total weight loss, delay or attenuate the plateau, and improve body composition compared to monotherapy. This dual-action strategy simultaneously targets both sides of the mass balance equation. Promising candidates for the NMO component include SGLT2 inhibitors (via direct glucosuria), activin/myostatin pathway inhibitors (via lean mass preservation), and mitochondrial uncouplers (via increased k through enhanced thermogenesis), with SGLT2 inhibitors currently offering the highest near-term translational potential. Recent phase 2 data with the myostatin inhibitor apitegromab combined with tirzepatide provides the first direct clinical evidence supporting the MBM prediction that NMO-stabilizing agents enhance body composition during GLP-1-induced weight loss. This MBM-based rational polypharmacy represents a paradigm shift from viewing obesity as a disorder of energy surplus to treating it as a disorder of mass flow dysregulation.
Engagement Phenotypes in a Real-World Tirzepatide-Based Dig-Ital Weight-Loss Program: Unsupervised Clustering of Self-Tracking, Human Coaching, and AI Conversational Support
In a clinical study, under strict clinical safety guardrails, structured automated conversational support may achieve outcome parity with human coaching, offering a highly scalable mechanism to complement pharmacologic obesity care.
Talay L, Xu C, Hom J, Swinckels L, Tan M, Alderete J, Ahuja N.
Background: and Objectives: Real-world adherence to medication-supported weight management programs is often low. While digital weight loss services (DWLS) provide multi-modal digital supports to improve engagement and counter attrition, existing literature frequently relies on unidimensional or binary classifications of user engagement. This study used unsupervised machine learning to identify distinct digital engagement phenotypes and evaluated their independent associations with 6-month weight loss outcomes in patients prescribed tirzepatide. Materials and Methods: This retrospective cohort study analyzed deidentified data from 9,470 medication-adherent, complete-case adult patients within an Australian DWLS who initiated tirzepatide between May 20 and December 2, 2025. K-means clustering was performed on four continuous, longitudinal usage metrics: weekly app logins, health coach messaging, automated assistant (JuneBot) messaging, and weight tracking. To evaluate the primary clinical endpoint - 6-month percentage weight loss - unadjusted pairwise comparisons (Tukey HSD) and a fully adjusted ordinary least squares multivariate linear regression model were executed to control for baseline demographic, clinical, and interim behavioral covariates. Results: Four stable engagement phenotypes emerged: non-engaged (n = 1,772), high health-coach engagement (n = 1,141), high JuneBot engagement (n = 1,472), and passive self-trackers (n = 5,085). In the multivariate regression model (Adjusted R2 = 0.3606, p < 0.001), all active phenotypes were strong independent predictors of weight loss success relative to the non-engaged baseline. The adjusted incremental weight loss premiums were similar between the automated conversational cohort (β = 2.28%, SE = 0.24, p < 0.001) and the human health-coaching cohort (β = 2.17%, SE = 0.26, p < 0.001), while passive self-trackers demonstrated a smaller independent premium (β = 1.67%, SE = 0.20, p < 0.001). Conclusions: In a real-world per-protocol cohort, active engagement in a DWLS is associated with significantly improved 6-month weight loss outcomes. Under strict clinical safety guardrails, structured automated conversational support may achieve outcome parity with human coaching, offering a highly scalable mechanism to complement pharmacologic obesity care.