Peptide Research Database
Access 6,710 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.
Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review.
In a case report, together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction.
Pasquariello T, Secondulfo F, Roscini AR, Nardi E, Prosperi E, Capasso G, Perna AF, Zacchia M
Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease. Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequential therapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist. We report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygous likely pathogenic BBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction-associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (-3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months. Following discontinuation of liraglutide, setmelanotide therapy was subsequently initiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10-40, 3-52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. Setmelanotide promoted clinically meaningful weight loss and improved liver, kidney, and metabolic parameters in an adult patient carrying BBS10-likely pathogenic variants. Together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction.
Loss of eIF3m aggravates myocardial ischemia/reperfusion injury via enhancing nitrative damage and inhibiting glycolytic reprogramming.
This study found our findings reveal the eIF3m-Mt2 axis as a new translational checkpoint that governs metabolic reprogramming and nitrative stress resistance in the injured heart, nominating it as a potential therapeutic target for myocardial I/R injury.
Wei Z, Zhao Y, Jia D, Gao R, Xiong W, Sun X, Weng X, Liu B, Song S, Luo W, Cui J, Hu K, Sun A, Ge J
The reprogramming of myocardial energy metabolism is critical for cardiac repair after ischemia/reperfusion (I/R) injury, yet the upstream translational control mechanisms remain elusive. Here, through multi-omics analysis of human failing hearts, we identify the mRNA regulator eIF3m as an essential factor for maintaining cardiac glycolytic flux post-I/R. We show that eIF3m, independently of the canonical eIF3 complex, stabilizes Mt2 and related stress-response mRNAs, ultimately protecting the key glycolytic activator Pfkfb3. Loss of eIF3m impairs the heart's adaptive shift toward utilizing glycolysis for energy, leading to contractile dysfunction. Mechanistically, eIF3m deficiency exacerbates excessive nitro-oxidative stress, which damages and inactivates the key glycolytic enzyme Pfkfb3. This damage is counteracted by the metallothionein Mt2, a direct binding partner of eIF3m. Our findings reveal the eIF3m-Mt2 axis as a novel translational checkpoint that governs metabolic reprogramming and nitrative stress resistance in the injured heart, nominating it as a potential therapeutic target for myocardial I/R injury.
Detection of NADH/NAD+ dysregulation in MELAS via diazo-carboxyl click derivatization mass spectrometry.
In a clinical study, although the β-hydroxybutyrate/acetoacetate ratio showed high sensitivity (95.7%), its overall diagnostic accuracy was limited by lower specificity.
Hu J, Liufu T, Li C, Zhao Q, Yu M, Yuan Y, Quan L, Chen Z, Wang Z
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder driven by mutations in mitochondrial or nuclear DNA, involving an altered NADH/NAD+-associated redox metabolism as a key pathological mechanism. The traditional metabolomic analyses in MELAS face sensitivity and sample volume limitations, particularly for carboxylic acid metabolites. This study employed a recently established diazo-carboxyl/hydroxylamine-ketone double-click derivatization (DQmB-HA) mass spectrometry method to overcome these barriers, enabling highly sensitive quantification of NADH/NAD+-related serum metabolites in minimal sample volumes. Using DQmB-HA mass spectrometry, we analyzed lactate, pyruvate, β-hydroxybutyrate, acetoacetate, α-hydroxybutyrate, and malate in 5-μL serum samples from each of the MELAS patients (n = 70), healthy controls (n = 29), and CPEO patients (n = 17). Individual metabolite levels were quantified, and the lactate/pyruvate ratio and β-hydroxybutyrate/acetoacetate ratio were used as surrogate indicators of cytoplasmic and mitochondrial NADH/NAD+ redox states, respectively. Following this, analyses were performed to assess between-group differences in these indicators and to determine their correlations with disease duration. MELAS patients exhibited significantly elevated lactate, β-hydroxybutyrate, α-hydroxybutyrate, and malate levels, together with increased lactate/pyruvate and β-hydroxybutyrate/acetoacetate ratios compared with healthy controls. Among the evaluated biomarkers, the lactate/pyruvate ratio achieved the highest diagnostic performance (AUC = 0.993, 95% CI = 0.979-1.000), followed by lactate (AUC = 0.976) and β-hydroxybutyrate (AUC = 0.864). Although the β-hydroxybutyrate/acetoacetate ratio showed high sensitivity (95.7%), its overall diagnostic accuracy was limited by lower specificity. However, none of these serum markers show a significant correlation with the disease duration course in MELAS patients. Relative to MELAS, lower concentrations of α-hydroxybutyrate (p < 0.001) and malate (p = 0.026) and elevated lactate/pyruvate ratio (p < 0.001) were observed in CPEO. The DQmB-HA method enabled high-sensitivity metabolomic profiling in low-volume clinical samples and revealed broad alterations in metabolites and metabolite ratios associated with NADH/NAD + -related redox metabolism in MELAS, providing a useful framework for metabolomic screening in mitochondrial diseases.
Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats.
In a rat study, collectively, our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists.
Petersen J, Merrild C, Holm SK, Kurgan N, Hassan S, Mathiesen CV, Börchers S, Svendsen C, D'Anna S, Andersen NR, Klein AB, Fritzen AM, Deshmukh AS, Pers TH, Clemmensen C
Peptide multi-receptor agonists have advanced obesity treatment, yet challenges remain in achieving maximal weight loss and metabolic control, especially in patients with obesity and type 2 diabetes. Here we demonstrate enhanced metabolic benefits of a combination therapy with retatrutide, a unimolecular GLP-1R/GIPR/GCGR tri-agonist, and cagrilintide, an AMLNR/CALCR co-agonist, in diet-induced obese male rats. Daily co-administration produces dose-dependent reductions in body weight and food intake that exceed both equimolar monotherapies and matched-dose comparator combinations incorporating semaglutide or tirzepatide. The combination therapy also improves circulating markers of metabolic health, including cholesterol, triglycerides and insulin levels. Pair-feeding and weight-matching studies reveal that the enhanced weight loss cannot be explained by reduced food intake alone and enable discrimination between weight-loss-dependent and drug-specific molecular responses. Plasma proteomic profiling highlights enrichment of bioenergetic processes with the combination therapy, whereas brain transcriptomic profiling identifies convergent central neuronal programmes linked to energy balance regulation. Collectively, our preclinical findings support five-receptor polypharmacology as a strategy for efficaciously lowering body weight and provide guidance for the design of next-generation unimolecular multi-receptor agonists.
Stressor- and Tissue-Specific Regulation of the Corticotropin-Releasing Factor System Across Epithelial Tissues in Rainbow Trout.
This study found overall, our results implicate the peripheral CRF system as a stressor- and tissue lining tissue-specific modulator of immune and osmoregulatory functions in teleosts.
Culbert BM, Pulford-Thorpe AE, Best C, Bernier NJ
The corticotropin-releasing factor (CRF) system is a major neural regulator of stress responses in vertebrates. However, stress-related roles for the CRF system in other tissues-and whether these roles vary between stressor types-remain unclear. To address this gap, we first characterized the CRF system in the gills and intestine of rainbow trout (Oncorhynchus mykiss) and then evaluated how it is transcriptionally regulated following either an immune (vaccination) or osmotic (seawater transfer) stressor. Additionally, since the CRF system is involved in food intake regulation, we also evaluated whether feeding state affects the intestinal CRF system. Vaccination against Vibrio anguillarum caused increases in intestinal CRF binding protein transcripts paired with reductions in ligand (crfa2) and receptor (crfr1b) transcripts but did not affect transcript levels of CRF system components in the gills. In contrast, seawater transfer caused the abundance of most CRF system transcripts to increase in the middle (but not posterior) portion of the intestine, while transcript levels of CRF binding proteins and receptors in the gills declined. Finally, levels of CRF system transcripts in the intestine varied with feeding state in a region-specific manner. In the middle intestine, transcript levels of most components declined with fasting and increased when feeding was resumed, whereas the opposite pattern occurred in the posterior intestine. Overall, our results implicate the peripheral CRF system as a stressor- and epithelial tissue-specific modulator of immune and osmoregulatory functions in teleosts.
A multicenter real-world study on the safety and effectiveness of the glucagon-like peptide-1 receptor agonist (liraglutide) in adolescents with obesity in Taiwan.
This study found in adolescents with obesity in Taiwan, liraglutide at doses below 3.0 mg/day was well-tolerated, and reductions in BW, BMI, and BMI standard deviation score were observed. Evaluated the safety and effectiveness of GLP-1 receptor agonist (liraglutide) in adolescents with obesity in clinical practice in Taiwan.
Chiu CF, Chou CK, Hu SW, Huang KC, Wu YL, Wu HF, Liu YL, Yang YC, Chen HL, Yeung CY
Pediatric obesity is linked to many metabolic complications and has limited treatment options. We evaluated the safety and effectiveness of GLP-1 receptor agonist (liraglutide) in adolescents with obesity in clinical practice in Taiwan. We conducted a prospective study (NCT06283641) across 14 hospitals and clinics from February 2024 to March 2025 evaluating adolescents receiving liraglutide at baseline, week 13, and week 26. Demographics, and safety and effectiveness outcomes, including incidence proportions of adverse events and adverse drug reactions, and changes in body weight and body mass index, were assessed. Among 41 participants, 22 (53.7%) were male, with mean age (±standard deviation) 13.9 ± 1.8 years, body weight (BW) 88.5 ± 19.3 kg, and body mass index (BMI) 33.4 ± 5.1 kg/m2. Nineteen (46.3%) had medical history of hepatic impairment. Mean daily and maximum doses were 1.4 ± 0.5 mg/day and 1.8 ± 0.7 mg/day, respectively, throughout 128.3 ± 56.0 days; 14.4% escalated to 3.0 mg/day. Overall respective incidence proportions of adverse events and adverse drug reactions were 19.5% (8/41; all mild) and 9.8% (4/41; 6 events), respectively. Gastrointestinal events were most frequent, followed by injection site-related events. No treatment discontinuation resulted from intolerance. Mean respective losses in BW, BMI, and BMI standard deviation score at weeks 13 and 26 were -2.7 ± 3.8 kg (p = 0.0003), -1.3 ± 1.4 kg/m2 (p < 0.0001), and -0.2 ± 0.2 (p < 0.0001); and -4.4 ± 5.7 kg (p = 0.0015), -1.9 ± 2.1 kg/m2 (p = 0.0004), and -0.4 ± 0.3 (p < 0.0001), respectively. In adolescents with obesity in Taiwan, liraglutide at doses below 3.0 mg/day was well-tolerated, and reductions in BW, BMI, and BMI standard deviation score were observed.
Effects of GLP-1 receptor agonists on body weight and cardiovascular outcomes: a review.
In a research review, overall, GLP-1RAs represent a therapeutic option for cardiovascular prevention across a broad spectrum of patients at high-risk for or with established CVD.
van Maren SJF, van Doorn EPM, Smits MM, Tack CJJ, van Rossum EFC, El Messaoudi S
Obesity is a rapidly increasing global health challenge that is strongly linked to the cardiorenometabolic syndrome, cardiovascular morbidity, and mortality. Lifestyle interventions remain the cornerstone of treatment, but average long-term weight loss is modest and durable weight maintenance is often limited. Bariatric surgery is not suitable for all patients, and substantial weight regain occurs in a considerable proportion over time. Glucagon-like peptide‑1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes (T2D), have emerged as potent agents for weight reduction and cardiometabolic risk improvement. By enhancing glucose-dependent insulin secretion, suppressing appetite, improving lipid metabolism, and exerting anti-inflammatory, endothelial, and haemodynamic effects, GLP-1RAs influence multiple pathways relevant to cardiovascular disease.Across large cardiovascular-outcome trials, GLP-1RAs consistently reduce major adverse cardiovascular events (MACE), all-cause mortality, and heart-failure hospitalizations in individuals with T2D. In populations with overweight or obesity without diabetes, semaglutide, as shown in the SELECT trial, has demonstrated significant cardiovascular risk reduction, partly independent of weight loss. Overall, GLP-1RAs represent a therapeutic option for cardiovascular prevention across a broad spectrum of patients at high-risk for or with established CVD. This review provides a comprehensive overview of the pleiotropic cardiovascular effects associated with GLP-1RAs and discusses their potential integration into cardiovascular care.
The association of perinatal factors with molar hypomineralization and caries - Results from an observational study.
This study found the results support the assumption that perinatal factors - particularly operative vaginal delivery, secondary Cesarean section, and associated anaesthetic procedures - are positively associated with MH.
Kühnisch J, Ammar N, Fresen KF, Gaballah R, Pernegger E, Schill HI, Amend S, Heinrich J, Krämer N
Molar hypomineralization (MH) and caries are prevalent hard tissue defects. With respect to the unclear MH-etiology this observational study aimed to comprehensively investigate perinatal factors associated with both MH and caries. A sample of 5418 school-aged children from Bavaria, Germany, was clinically examined, and their parents were asked to complete a questionnaire covering perinatal factors, using medical records (Maternal Health Record and Child Health Examination Booklet). A total of 1315 questionnaire were available for analysis using marginalized zero-inflated negative binomial regression. Incidence rate ratios (IRRs) and adjusted odds ratios (aORs) were calculated. Among all individuals, 20.0% (N = 263) were diagnosed with MH, and 39.9% (N = 525) were diagnosed with caries. Advanced parental age emerged as a significant risk factor for MH (aOR: 1.24 (1.02-1.50)), as did the use of general (IRR: 1.95 (1.16-3.27)) or regional anesthesia (aOR: 1.41 (1.16-1.71)). An increased risk of MH was also observed in children born via secondary Cesarean section (aOR: 1.43 (1.09-1.87)) or operative vaginal delivery (IRR: 1.37 (1.02-1.84)). Conversely, oxytocin administration for labour induction was associated with a lower rate of MH (aOR: 0.80 (0.66-0.96)). With respect to caries, the investigated variables showed weak, inconsistent, or no significant associations. The results support the assumption that perinatal factors - particularly operative vaginal delivery, secondary Cesarean section, and associated anaesthetic procedures - are positively associated with MH. Future studies are warranted to confirm the reported associations. Etiology of MH remain unclear but perinatal factors may have a potential influence.
Comparative effects of central and peripheral PDE10A inhibition on weight gain following semaglutide cessation in diet-induced obese mice
In a mouse study, these findings establish BEN-8744 as pharmacologically active through a food-intake-independent mechanism consistent with increased energy expenditure, but indicate that its efficacy is modest relative to additional central PDE10A inhibition.
Grey J, Whitton B, Mulvaney K.
Obesity is a chronic disease of disordered energy balance for which durable weight management remains an unmet need. The rise in use of anorectic therapies, such as incretin analogues, now particularly highlights the need for therapies which maintain weight loss after cessation of effective pharmacotherapy. Phosphodiesterase 10A (PDE10A) inhibition increases energy expenditure and promotes white adipose tissue browning in preclinical models, providing a mechanistic rationale for its therapeutic application. Two complementary studies in male diet-induced obese C57BL/6J mice were conducted to evaluate its pharmacological activity. In a 21-day dose-response study, BEN-8744, an orally bioavailable, peripherally-restricted, PDE10A inhibitor, significantly attenuated body weight gain relative to vehicle at all doses tested. In a 40-day weight maintenance study, mice pre-treated with semaglutide were switched to vehicle-only, BEN-8744, the brain-penetrant PDE10A inhibitor mardepodect or continued semaglutide. Mardepodect was comparable to continued semaglutide, significantly suppressing food intake and weight gain. BEN-8744 showed numerically less gain than vehicle but this difference did not reach statistical significance. Contrary to mardepodect treatment, BEN-8744 also did not significantly improve glucose tolerance or serum insulin. These findings establish BEN-8744 as pharmacologically active through a food-intake-independent mechanism consistent with increased energy expenditure, but indicate that its efficacy is modest relative to additional central PDE10A inhibition. Central PDE10A target engagement is essential for a sustained anti-obesity effect.
DUTCH weight control in atrial fibrillation study (DUTCH-WAIST) : Design and rationale of a randomised controlled trial.
In a clinical study, investigates whether treatment of overweight with semaglutide, as an adjunct to lifestyle intervention, enhances rhythm control in AF patients with first detected persistent AF and overweight, offering a potential new approach to reducing AF burden and cardiovascular risk in this population.
Voorhout L, Pisters R, Huisman M, Klok E, Rutten F, Geersing GJ, Tieleman R, Cornel JH, Schut A, Tijssen J, van Bon A, Hemels M
Obesity is a well-established and highly prevalent risk factor for atrial fibrillation (AF) and its progression by promoting structural and electrical atrial remodelling, leading to AF recurrence and persistence. Weight loss is expected to reverse atrial remodelling and improve rhythm control. Optimal strategies for weight management are, however, under-explored. To quantify the effect of clinically meaningful weight loss on rhythm control in overweight patients with first detected persistent AF. A multicentre, double-blind, randomised, placebo-controlled trial evaluating semaglutide 2.4 mg once weekly versus placebo, in addition to combined lifestyle intervention (CLI), during a one-year period. Adults with a BMI > 30 kg/m2, or BMI > 27 kg/m2 with a weight-related comorbidity, and first detected (< 6 months) persistent AF scheduled for electrical cardioversion. Weekly subcutaneous injections of semaglutide 2.4 mg or placebo, alongside CLI and standard AF care in both groups. The co-primary outcome is (i) a hierarchical assessment of rhythm status at one year, ranking patients by severity from arrhythmic death to sinus rhythm without any additional rhythm control support. (ii) the composite of either persistent atrial fibrillation on ECG, catheter ablation for AF, arrhythmic death, or any serious adverse event due to anti-arrhythmic drugs occurring within 1 year. This study investigates whether treatment of overweight with semaglutide, as an adjunct to lifestyle intervention, enhances rhythm control in AF patients with first detected persistent AF and overweight, offering a potential new approach to reducing AF burden and cardiovascular risk in this population.