Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Effect of Semaglutide on Measured vs Estimated Glomerular Filtration Rate.
Nephrol Dial Transplant
Rafal Yahya, Esben Iversen, Suvanjaa Sivalingam +7 more
Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for its glucose-lowering effects in people with type 2 diabetes (T2D), as well as its cardiovascular and kidney-protective properties. However, it remains unclear whether semaglutide influences blood concentrations of endogenous filtration markers like creatinine, cystatin C, beta-trace protein (BTP), and beta-2 microglobulin (B2M). We investigated the effect of semaglutide on these filtration markers and the performance of estimated glomerular filtration rate (eGFR) equations compared with measured glomerular filtration rate (mGFR).
Current Concepts in Perioperative Guidance and Outcomes in Hand Surgery Patients Taking Glucagon-Like Peptide-1 Receptor Agonists.
J Hand Surg Am
Ethan Y Song, M Stephen Melton, Warren Hammert +2 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have rapidly increased in use for diabetes management and weight loss, coinciding with the rising prevalence of obesity and diabetes among patients undergoing hand surgery. Growing perioperative concerns of delayed gastric emptying and aspiration risk have prompted evolving guideline recommendations and clinical uncertainty surrounding surgical planning. Current evidence on GLP-1 RA usage and outcomes in hand and orthopedic literature remains limited, but multiple studies report no notable increase in postoperative complications. There may be potential benefits to GLP-1 RA in surgical outcomes, possibly related to reduced systemic medical morbidity and improved metabolic control. As there still are substantial limitations in the medical literature on the effects of GLP-1 RA, questions remain regarding optimal perioperative medication management, effects on bone and wound healing in the context of rapid weight loss, and anesthesia-related risk. Yet, as GLP-1 RA exposure becomes increasingly common, hand surgeons must understand the pharmacology, risk profile, and emerging evidence to guide individualized decision-making and ensure safe perioperative management for patients.
GLP-1 Agonists and Risk of Atrial Fibrillation in Non-Dialysis Chronic Kidney Disease.
Cardiovasc Drugs Ther
Parth Dhamelia, Ninad Khandekar, Srikanth Vallurupalli +5 more
GLP1 receptor agonists (GLP-1 RAs) improve cardiorenal outcomes in chronic kidney disease (CKD) patients with obesity or type 2 diabetes. Whether GLP-1 RAs reduce risk of atrial fibrillation (AF) in CKD patients, especially in absence of diabetes or obesity, is unclear.
Efficacy of tirzepatide versus SGLT2 inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD): a multicenter propensity-matched real-world study.
Hepatol Int
Ibrahim Khalil, Pallab Sarker, Nabila Nur +6 more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with significant cardiometabolic and hepatic risks. Tirzepatide, a dual GLP-1/GIP receptor agonist, shows promise in MASLD, but real-world comparative data against sodium-glucose cotransporter-2 inhibitors (SGLT2is) are lacking.
Synthesis, Characterization, and Antidiabetic Evaluation of Sequence-Modified Liraglutide Analogs in a Drosophila melanogaster Model.
Biopolymers
Tamira Ravi, Kalpanarani Dash, Deep Kumar Barman +3 more
Liraglutide, a glucagon-like peptide-1 receptor agonist, is widely used as a therapeutic macromolecule for the treatment of type 2 diabetes; however, its large-scale production is limited by high manufacturing costs and the frequent occurrence of closely related deletion impurities during synthesis. In the present study, we describe a novel, impurity-controlled, and industrially feasible synthetic strategy for liraglutide and its sequence-modified analogs. This method utilizes solution-phase incorporation of Pal-γ-Glu-OtBu in combination with a preassembled Boc-His (Boc)-Ala-Glu (OtBu)-OH tripeptide fragment, effectively minimizing the formation of des-His, des-Ala, and des-Glu impurities. The optimized protocol enabled the production of liraglutide and its analogs with consistent isolated yields and high chromatographic purity (> 95% by RP-HPLC), suitable for subsequent biological evaluation. The antidiabetic potential of liraglutide and three sequence-modified analogs, Lira (Trp-O25), Lira (desGly31), and Lira (Glu17), was evaluated using a Drosophila melanogaster model of high-sucrose diet induced diabetes. Among these, Lira (Glu17) exhibited the most pronounced metabolic improvements, significantly reducing free glucose (p < 0.001), trehalose (p < 0.001), and triglyceride levels (p < 0.001) when compared to diabetic controls. Furthermore, this analog effectively decreased lipid accumulation and reactive oxygen species in larval gut tissues and enhanced locomotor performance in both larva and adult flies. While Lira (Trp-O25) also demonstrated beneficial effects, Lira (desGly31) showed comparatively limited efficacy. Collectively, this study presents a cost-effective and impurity-controlled synthetic platform for liraglutide production and identifies Lira (Glu17) as a promising analog with enhanced antidiabetic activity, offering valuable insights for peptide manufacturing and GLP-1-based therapeutic development.
Physiologically Based Pharmacokinetic Modeling to Predict the Pharmacokinetics of Sacubitril/Valsartan in the Elderly with Renal or Hepatic Impairment Population.
J Clin Pharmacol
Jiaqi Shao, Ying Jin, Yingying Yang +5 more
This study developed and validated a whole-body physiologically based pharmacokinetic (PBPK) model for sacubitril/valsartan and its active metabolite LBQ657. The model, which incorporates key transporter-mediated clearance pathways, demonstrated robust predictive performance upon validation with clinical data from healthy, renally impaired, and hepatically impaired populations. Simulations using this validated model provided quantitative predictions of steady-state exposure in elderly populations with organ impairment under label-recommended dosing. The results mechanistically confirmed the selective increase in drug exposure driven by organ dysfunction: renal impairment disproportionately elevated LBQ657 exposure, whereas hepatic impairment predominantly increased valsartan exposure. A critical finding was the nuanced interaction between aging and organ impairment, where advanced age selectively exacerbated the exposure of the drug component cleared by the relatively intact organ. This work highlights the potential challenge of balancing exposure for both components when adjusting the dose of this fixed-dose combination in patients with organ dysfunction. The established PBPK model serves as a valuable quantitative tool for informing personalized dosing strategies and supporting clinical decision-making for vulnerable elderly patients with renal or hepatic impairment.
Structural and cellular mechanisms of mucus plugging in the larger airways.
Chin Med J Pulm Crit Care Med
Zheqing Hu, Liyuan Yang, Yabo Ma +2 more
Intractable mucus plugging drives mortality in cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). While surface metaplasia narrows small airways, the massive volumetric reservoir capacity of hypertrophied submucosal glands (SMGs) dictates catastrophic mucus plugging in the larger airways. This review proposes a flush-load model to explain this structural failure: a biophysical imbalance in which SMG serous fluid secretion (the flush) is insufficient to hydrate and clear the burden of high-molecular-weight mucins (the load), leading to osmotic compression, ciliary collapse, and intractable luminal occlusion. The review delineates the disease-specific etiologies of this imbalance. In CF, dysfunction of ion channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channels (ENaC), causes mechanical uncoupling and mucin 5B (MUC5B) tethering to glandular ducts. In asthma, Type 2 inflammation disrupts the glandular stem cells, driving an explosive release of mucin. In COPD, epidermal growth factor receptor (EGFR)-driven remodeling and senescent inflammaging perpetuate chronic hypersecretion. Ultimately, anchored MUC5B strands from hypertrophic SMGs structurally integrate with surface-derived mucin 5AC (MUC5AC), forming an intractable adhesive mesh. Synthesizing these insights, we advocate shifting the therapeutic paradigm from symptomatic downstream clearance to upstream, disease-modifying interventions that target the glandular stem cell niche, restore ion channel homeostasis, and correct coordinated airway surface dysfunction.
[Clinical application value of sST2 in patients with heart failure].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
Siyao Li, Haoneng Tang, Ruohong Chen +1 more
Accurate diagnosis and prognostic assessment of heart failure are crucial for improving patients' quality of life. This study aims to investigate the clinical value of serum soluble growth stimulation expressed gene 2 protein (sST2) levels in patients with heart failure, with and without obesity/overweight.
Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus: a network meta-analysis based on clinical trials.
Front Pharmacol
Xichao Wu, Yujiao Yang, Xueyan Cui +2 more
This study systematically assessed the efficacy and safety of 15 incretin-based therapies (IBTs) for type 2 diabetes mellitus (T2DM), including mono- (GLP-1RA), dual- (GIP/GLP-1RA or GLP-1/GCGR), and triple- (GIP/GLP-1/GCGR) receptor agonists, and explored how dosage and treatment duration affect clinical outcomes to support individualized treatment decisions.
Impact of incretin therapies on biochemical and imaging outcomes in metabolic dysfunction-associated steatotic liver disease.
Am J Prev Cardiol
Nicole Ann Tesoro, Frederick Berro Rivera, Nathan Ross B Bantayan +11 more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition. Incretin therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and emerging dual agonists, have shown promise in improving steatohepatitis.
Longitudinal 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) Findings in Korsakoff Syndrome After Rapid Weight Loss During Tirzepatide Therapy: A Case Report.
Cureus
Viviane T Crelier, Alexandra S Vidal, Nathane B Rezende +4 more
We report a case of a 50-year-old man with obesity and chronic alcohol use disorder who developed Korsakoff syndrome in the setting of rapid weight loss temporally associated with tirzepatide therapy, a dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonist. Within weeks of treatment initiation, he presented with profound memory impairment and anosognosia. Initial brain magnetic resonance imaging (MRI) was unremarkable, but 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed hypometabolism in the mammillary bodies with progressive involvement of the thalamus and brainstem. Despite intravenous thiamine replacement, cognitive deficits persisted. This case raises concern that rapid weight loss and reduced nutritional intake during GLP-1-based therapy may contribute to the development of Wernicke-Korsakoff syndrome in vulnerable individuals, particularly those with chronic alcohol use disorder, and underscores the importance of nutritional assessment and consideration of thiamine supplementation when initiating these treatments.
Prolactin receptor overexpression in pregnancy-associated Cushing syndrome and functional implications.
JCEM Case Rep
Masamitsu Naka, Kazuki Ishiwata, Sawako Suzuki +3 more
Cushing syndrome (CS) during pregnancy is rare but is associated with substantial maternal and fetal risks. Although aberrant activation of G protein-coupled receptors (GPCRs), particularly the luteinizing hormone/human chorionic gonadotropin receptor, has been implicated in pregnancy-related hypercortisolism, non-GPCR mechanisms remain incompletely defined. We report a case of adrenocorticotropic hormone-independent CS during pregnancy caused by a cortisol-producing adrenocortical adenoma. Integrative molecular analyses of the resected tumor, including ribonucleic acid sequencing and immunohistochemistry, demonstrated increased expression of the prolactin receptor (PRLR) compared with adjacent normal adrenal tissue. PRLR is a member of the type I cytokine receptor family and is expressed in normal adrenal glands; however, its potential role in adrenal tumors has not been well characterized. To examine its functional relevance, primary cell cultures derived from independent cortisol-producing adenomas from nonpregnant women were treated with recombinant prolactin (PRL). PRL induced a dose-dependent increase in both cortisol secretion into the culture medium and intracellular cortisol levels. Following unilateral adrenalectomy, hypercortisolism resolved, and maternal and neonatal outcomes were favorable. These data provide molecular and functional evidence supporting a contributory role of PRLR in pregnancy-associated hypercortisolism, potentially triggered by physiological PRL elevations during gestation.
Enhanced Stability and Transdermal Delivery of Semaglutide Using an L-Arginine Based Dissolving Microneedle System.
AAPS PharmSciTech
Priyanka Panchal, Snehal Daware, Yi Guo +4 more
Glucagon-like peptide-1 agonists, especially Semaglutide (SMG), have revolutionized the management of diabetes and obesity, yet its clinical application is hindered by challenges in oral bioavailability and patient adherence to injectable formulations. Transdermal delivery offers a promising alternative, and this study explores dissolving microneedle (DMN) technology for SMG administration. PETOX is a water-soluble polymer utilized for the fabrication of dissolving microneedles and unique stabilization of SMG by incorporating L-arginine. Our study presents the first comprehensive investigation of L-arginine as an excipient in dissolving microneedles to enhance peptide integrity and stability. This study focuses on the development and characterization of DMN arrays formulated with a polymeric blend of hyaluronic acid, PETOX, and L-arginine, designed for the transdermal delivery of SMG. The SMG loaded microneedles (SMG-DMNs) exhibit robust mechanical strength (3.47 N/needle; fracture force), excellent Parafilm M® insertion (> 50% at 450 μm depth), and drug release over 12 h. Extensive SMG-DMNs characterization include ex-vivo porcine skin insertion, scanning electron microscopy, confocal microscopy, and unique agarose-based dissolution model showed effective optimization of polymeric matrix for SMG, ensuring better insertion capabilities. The florescence imaging verified efficient transdermal deposition and penetration of dye suggesting potential transdermal delivery of SMG upon insertion. While the DMN approach addresses key barriers such as low oral bioavailability, injection-related discomfort and patient compliance; challenges persist regarding loss of therapeutic activity and stability of peptide. Nevertheless, DMN technology presents a promising, patient-friendly alternative for peptide therapeutics, with the potential to significantly improve outcomes in T2DM and obesity management.
Appetite Suppression by GLP-1 Receptor Agonists: Role of Delayed Gastric Emptying.
Obesity (Silver Spring)
Mark I Friedman, W Scott Harmsen, Michael Camilleri
This study aimed to evaluate relationships between delayed gastric emptying and appetite suppression during treatment with liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA).
The Preparation and Physicochemical Characterization of a Triple Synergistic Nanoplatform Designed for Targeted Subcutaneous Delivery of Sitagliptin with Potential for β-Cell Preservation.
AAPS PharmSciTech
Mo'tasem M Alsmadi, Rana Obaidat
Effective diabetes management necessitates innovative strategies that simultaneously stimulate β-cell growth and prevent apoptosis. While sitagliptin is an established therapeutic, its clinical utility is often hampered by suboptimal oral bioavailability and a lack of site-specific delivery. This research details the development and in vitro assessment of Sita-Ex-Cs-SeNPs, a subcutaneous nanocarrier composed of sitagliptin-loaded chitosan-selenium nanoparticles conjugated with exenatide. The platform is engineered to leverage GLP-1 receptor affinity for pancreatic targeting and utilize selenium's intrinsic antioxidant properties to achieve therapeutic synergy. We employed the ionotropic gelation technique to encapsulate sitagliptin and integrate exenatide and selenium into a unified, stable delivery system. The resulting nanoparticles exhibited a spherical architecture with an average diameter of 314.1 nm and a zeta potential of + 18.7 mV. We achieved a high encapsulation efficiency of 98%. Analytical techniques (DSC and PXRD) confirmed that sitagliptin transitioned to an amorphous state, while FTIR validated successful peptide conjugation. Release kinetics followed the Weibull model, demonstrating a controlled biphasic profile (57% over 24 h) that significantly extends the therapeutic window compared to the free drug. Sita-Ex-Cs-SeNPs offer a promising, biocompatible approach for targeted diabetes intervention. Although in vitro results confirm stable sustained release, subsequent in vivo trials are essential to validate their efficacy in β-cell preservation.
[Therapeutic mechanism of combination of Epimedii Folium and Ligustri Lucidi Fructus for glucocorticoid synthesis-restricted asthma in rats].
Zhongguo Zhong Yao Za Zhi
Zai-Na Ma, Ren-Hui Liu, Yong-Hao Xie +4 more
This study aims to elucidate the therapeutic effects and mechanisms of the combination of Epimedii Folium and Ligustri Lucidi Fructus on glucocorticoid(GC) synthesis-restricted asthma in rats. The classic asthma model induced by ovalbumin(OVA) sensitization and challenge, a complex asthma animal model with specific suppression of hypothalamic-pituitary-adrenal(HPA) axis at the synthesis level of endogenous GC by intraperitoneal administration of metyrapone(Met), was established. This model was designed to simulate the pathological condition of GC resistance or insufficient synthesis encountered in clinical practice. Male SD rats were randomly assigned into six groups: normal, Met, asthma+Met, Epimedii Folium, Ligustri Lucidi Fructus, and Epimedii Folium+Ligustri Lucidi Fructus, followed by a one-week drug treatment via gavage. Serum levels of corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH), corticosterone(CORT), and cortisol(COR) were assessed. Targeted metabolomics was adopted to detect endogenous GC metabolism levels in the urine. Immunohistochemical staining was employed to assess the expression of hydroxysteroid dehydrogenase(HSD) 11B1,HSD11B2, cytochrome P450 family 11 subfamily B member 1(CYP11B1), and steroidogenic factor 1(SF1) in the lung and adrenal gland. Western blot was employed to quantify the expression of related proteins in the liver tissue. The results showed that Epimedii Folium and/or Ligustri Lucidi Fructus elevated the serum concentrations of CRH, ACTH, CORT, and COR in model rats, partially reversed abnormalities in the urinary GC metabolic profile, and upregulated the expression of key synthetic and metabolic enzymes(HSD11B1, HSD11B2, CYP11B1, and SF1) in the lung, liver, and adrenal gland. The combination of Epimedii Folium and Ligustri Lucidi Fructus exerts multi-faceted regulatory effects on both the HPA axis and GC synthesis/metabolism in the peripheral tissue, synergistically ameliorating endogenous GC dysregulation in synthesis-restricted asthma. These findings suggest the potential therapeutic value of this combination against GC resistance and related disorders.
Liver fibrosis in metabolic dysfunction-associated steatotic liver disease: epidemiology, risk stratification and therapeutics.
BMJ Open Gastroenterol
Fuliang Li, Hongmei Li, Dulguun Juramt +3 more
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide and is tightly linked to cardiometabolic comorbidities. A major clinical focus on MASLD is the detection of hepatic fibrosis, which most strongly predicts liver-related events, hepatocellular carcinoma risk and mortality. While lifestyle modification and sustained weight loss remain foundational, therapeutic innovation has rapidly expanded, shifting the metabolic dysfunction-associated steatohepatitis (MASH) treatment landscape towards targeted pharmacotherapies that address metabolic stress, inflammation and fibrogenesis, particularly for moderate/advanced fibrosis (i.e., F2/F3 fibrosis and cirrhosis). This review summarises the burden and systemic complications of MASLD, highlights endocrine influences that modulate hepatic steatosis and disease severity and emphasises the central role of fibrosis staging and non-invasive risk stratification in clinical decision-making. We then synthesise emerging pharmacotherapies across key mechanistic axes, including incretin-based agents (GLP-1 receptor agonists and dual/triple agonists), hepatocyte-directed metabolic modulators (thyroid hormone receptor-β agonists, fatty acid synthase inhibitors, acetyl-CoA carboxylase and other de novo lipogenesis inhibitors), bile acid pathway therapies (FXR agonists) and pleiotropic metabolic-fibrotic regulators (fibroblast growth factor 21 [FGF21] analogues and peroxisome proliferator-activated receptor [PPAR] agonists). We also discuss combination strategies, candidate agents with potential direct antifibrotic activity and the growing role of genetic risk stratification and hepatocyte-targeted oligonucleotide therapeutics. Finally, we outline current surrogate endpoints used in clinical trials and propose future directions towards stage-specific, mechanism-informed and combination regimens to achieve persistent MASH resolution and meaningful fibrosis regression.
Regenerative Index: a method to assess muscle regeneration in patients with Duchenne muscular dystrophy.
Skelet Muscle
Johnathan K Smid, Charis A McPherson, Jacob G Monast +3 more
Duchenne muscular dystrophy (DMD) is a devastating disease manifested in skeletal muscle by repetitious myonecrosis and regeneration. Because the regenerative process is closely linked to the cumulative severity of muscle damage, which is variably distributed within and between muscle groups, accurately quantifying muscle regeneration has remained a significant challenge.
Population dynamics analysis of an industrial methanotrophic consortium based on Methylococcus capsulatus KN2 using AI technologies.
Front Microbiol
Maksim V Zakhartsev, Dmitriy A Pavlov, Igor Y Oshkin +2 more
Monitoring the population dynamics of industrial methanotrophic bacterial consortia is critical for optimization of single-cell protein (SCP) production from natural gas. Traditional manual microscopy is labor-intensive, subjective, and limited in throughput. AI-based computer vision offers a promising alternative for automated, quantitative analysis of cell morphotypes in mixed cultures.
Regarding IL-15 Plus Thymosin α1 Reduces Senescent Hepatic CD8+ T Cells in Hepatocellular Carcinoma via PI3K/AKT Suppression.
J Gastroenterol Hepatol
Ilker Sengul, Demet Sengul
The investigation by Wu et al. into the synergistic application of interleukin-15 (IL-15) and thymosin 1 (T1) marks a pivotal advancement in addressing CD8+ T-cell immunosenescence within the hepatocellular carcinoma (HCC) microenvironment. By utilizing a clinically relevant aged orthotopic model, the authors demonstrate that a dual-compartment strategy-leveraging central replenishment and peripheral rescue-significantly attenuates tumor progression. However, a critical reappraisal of the functional data suggests that the observed therapeutic benefit may stem from a "strategic change of the guard" rather than a literal phenotypic reversal of senescent cells. Specifically, the persistently low Granzyme B expression within terminally differentiated CD27-CD28- populations across treatment arms implies that efficacy is primarily driven by T1-mediated thymic output and the IL-15-induced expansion of newly recruited, non-senescent effectors. Furthermore, the mechanistic focus on PI3K/AKT pathway suppression as a "therapeutic reset" introduces a significant metabolic paradox. Although effective in breaking the cycle of chronic tonic signaling that defines the senescent state, systemic attenuation of this axis risks blunting the acute metabolic fitness required for robust immune responses in an already fragile aged population. This commentary emphasizes that distinguishing between population replacement and cellular rejuvenation is paramount for predicting long-term durability. Future clinical translations should look beyond the CD8+ compartment to integrate the pleiotropic effects of these agents on the broader immune landscape to ensure both oncological efficacy and systemic immunological safety.