RPEP-10139 · 2025Tirzepatide provided greater health benefits at lower costs than semaglutide for patients with knee osteoarthritis and obesity, with an incremental cost-effectiveness ratio (ICER) of $57,400 per quality-adjusted life-year (QALY) versus diet and exercise. At a $100,000 per QALY willingness-to-pay threshold, tirzepatide had a 64% probability of being cost-effective compared to 34% for semaglutide.
For patients eligible for bariatric surgery, Roux-en-Y gastric bypass (RYGB) provided even greater health benefits at lower costs than both GLP-1 drugs, with an ICER of $30,700 per QALY versus laparoscopic sleeve gastrectomy.
Betensky, Daniel J; Smith, Karen C; Katz, Jeffrey N; Yang, Catherine; Hunter, David J; Collins, Jamie E; Feldman, Candace H; Messier, Stephen P; Kim, Jason S; Selzer, Faith; Paltiel, A David; Losina, Elena · Modeling
RPEP-10140 · 2025Intestinal stretch — independent of nutrients and gut hormones — suppresses food intake and improves glucose tolerance in mice. Using mannitol (a nonnutritive substance) to selectively stretch the intestine, researchers showed this mechanical signal acutely reduces eating and improves oral glucose tolerance without relying on GLP-1 signaling or vagal mechanosensation. Critically, diet-induced obesity impaired this stretch response, reducing both feeding suppression and neuronal activation in the nucleus of the solitary tract (NTS). Both dietary weight loss and vertical sleeve gastrectomy (VSG) restored the impaired stretch-induced feeding suppression and enhanced NTS neuronal activation. VSG specifically heightened NTS neuronal activation in response to oral (but not injected) glucose.
Bethea, Maigen; Cook, Tyler; Mommandi, Marwa; McClennan, Andrew; Martin, Allison; Hendrix, Jasmine J; Hutch, Chelsea R; Lewis, Alfor; Seeley, Randy J; Fenselau, Henning; da Silva Teixeria, Silvania; Sandoval, Darleen A ·
RPEP-10142 · 2025Among 95 reviewers reporting both weight loss amounts and treatment duration, users taking semaglutide for more than 60 days achieved mean weight loss of 32.2 ± 3.1 lbs (14.6 kg).
The most frequently mentioned side effects were: nausea (46.9%), headache (18.4%), vomiting (14.3%), fatigue (9.2%), and dizziness (4.8%). Sentiment analysis showed the highest satisfaction scores in the ≤30-day group (mean: 3.38 on a 5-point scale). Topic modeling identified dominant themes: appetite suppression, medication cost and access barriers, and long-term experiences. Cluster analysis revealed distinct user profiles including a 'super-responder' group and a side-effect-burdened group.
Bhagavathula, Akshaya Srikanth ·
RPEP-10147 · 2025The review maps the incretin co-agonist landscape across multiple drug classes. GLP-1 receptor agonists improve glycated hemoglobin, weight, lipid profiles, and liver fat, with many reducing major adverse cardiovascular events (MACE). The oral GLP-1RA orforglipron achieves approximately 15% weight reduction.
Tirzepatide, the first approved dual GIP/GLP-1 agonist, offers comparable efficacy with notably fewer gastrointestinal side effects than GLP-1 monoagonists. Triple agonists targeting GLP-1, GIP, and glucagon receptors (retatrutide, efocipegtrutide) have demonstrated the highest pharmacotherapy-achievable weight loss to date. Emerging combinations include GLP-1/amylin agonists (CagriSema, amycretin) and peptide YY/GLP-1 dual agonists.
Bhat, Sowrabha; Fernandez, Cornelius J; Lakshmi, Vijaya; Pappachan, Joseph M ·
RPEP-10149 · 2025The study presents the rationale and evidence for SYMBRAVO, a dual-pathway pharmacological approach combining rizatriptan (a triptan targeting CGRP-induced nociception via serotonin 5-HT1B/1D receptors) and meloxicam (a selective COX-2 inhibitor reducing inflammatory prostaglandins).
The authors argue that CGRP and COX pathways interact in migraine through neuroinflammatory crosstalk, where CGRP-mediated neurogenic inflammation amplifies COX-dependent prostaglandin production and vice versa. Targeting both simultaneously could improve efficacy, reduce the dose needed for each drug, and minimize side effects compared to monotherapy.
Bhatia, Vandana; Vikram, Vir; Rattan, Aditya; Chandel, Anjali; Ashawat, M S ·
RPEP-10154 · 2025Glycocalyx-mimetic supplementation significantly reduced heart failure risk scores (HF2) by a mean of -0.58 (95% CI: -0.83 to -0.33, adjusted p<0.001) as measured by urinary peptidomic classifiers. The supplement altered 17 urinary peptides, primarily decreasing collagen-derived fragments, suggesting improved extracellular matrix turnover. Coronary artery disease (CAD160) and chronic kidney disease (CKD273) risk scores were unchanged. Neither the fasting-mimicking diet nor placebo produced meaningful changes in any classifier.
Biglari, Sajjad; Yuan, Lushun; Mischak, Harald; Siwy, Justyna; Latosinska, Agnieszka; Banasik, Miroslaw; van den Berg, Bernard M ·
RPEP-10155 · 2025The review identifies GLP-1 receptor agonists as effective treatments that improve both metabolic and reproductive outcomes in PCOS. The key recommendation is that PCOS patients with insulin resistance and obesity would benefit most from combination therapy with metformin and GLP-1 receptor agonists, which provides comprehensive treatment for both the reproductive and metabolic aspects of the condition.
Other effective interventions include myoinositol (for ovarian function), resveratrol (metabolic and reproductive benefits), and bariatric surgery for severe obesity. Lifestyle modifications remain the first-line approach.
Bila, Jovan; Dotlic, Jelena; Andjic, Mladen; Ivanovic, Katarina; Micic, Jelena; Tulic, Lidija; Pupovac, Miljan; Stojnic, Jelena; Vukovic, Ivana; Ivanovic, Stefan ·
RPEP-10167 · 2025Using advanced solid-state NMR techniques, researchers revealed exactly how the host-defense peptide cathelicidin-2 attacks the cell wall of Aspergillus fumigatus, a drug-resistant fungus that causes life-threatening infections. The peptide disrupts galactosaminogalactan — a key component involved in the fungus's ability to cause invasive disease — and affects other polysaccharides and amino acids in the mobile cell wall domain.
With longer exposure, cathelicidin-2 also penetrates the rigid cell wall by enhancing water infiltration into normally hydrophobic regions, eventually reaching the plasma membrane. This two-phase attack — first targeting mobile wall components, then breaching rigid defenses — explains how the peptide can overcome the complex fungal cell wall barrier that makes antifungal drug development so challenging.
Bishoyi, Ajit Kumar; van Neer, Jacq; Bahri, Salima; Lorenz, Sophie; de Cock, Hans; Baldus, Marc · In Vitro / Mechanistic Study
RPEP-10169 · 2025PF14-Lys (a lysine-substituted analog of PepFect14) showed superior delivery of splicing-switching oligonucleotides and siRNA compared to the original PF14 in reporter cell lines. The alpha-helical structure of PF14 was found to be essential for delivery — mutations disrupting the hydrophobic or cationic face abolished nanoparticle formation and cell entry. PF14-Lys efficiently delivered miR-146a into human primary keratinocytes, downregulating target genes. Most importantly, subcutaneously administered PF14-Lys-miR-146a nanoparticles suppressed inflammatory responses in a mouse model of irritant contact dermatitis.
Biswas, Abhijit; Periyasamy, Kapilraj; Maloverjan, Maria; Porosk, Ly; Arya, Geeta; Mehta, Sudhichan; Andla, Hanna; Raid, Raivo; Kisand, Vambola; Rätsep, Margus; Wengel, Jesper; Rebane, Ana; Pooga, Margus ·
RPEP-10175 · 2025Among 5,173 individuals with BMI ≥27, those with obstructive coronary artery disease (≥50% blockage) had a 71% higher risk of cardiovascular events compared to those with no disease (adjusted HR: 1.71; 95% CI: 1.21-2.42; P = 0.002). At 4 years, event rates were 7.8% for obstructive CAD and 7.7% for extensive nonobstructive CAD — comparable to the 9.7% rate in the SELECT trial's control arm. The estimated number needed to treat with semaglutide was 66-67, close to SELECT's 56.
Blair, Camila V; Huck, Daniel; Besser, Stephanie A; Cardoso, Rhanderson; Shiyovich, Arthur; Berman, Adam N; Biery, David W; Weber, Brittany N; Petranovic, Milena; Nasir, Khurram; Hedgire, Sandeep; Plutzky, Jorge; Cannon, Christopher; Di Carli, Marcelo F; Ghoshhajra, Brian B; Trinquart, Ludovic; Blankstein, Ron ·
RPEP-10179 · 2025The review identifies several diabetes drugs with neuroinflammatory potential:
- Liraglutide (GLP-1 receptor agonist): Showed encouraging effects in regulating blood sugar while possibly lowering neuroinflammation; obese patients saw decreased neuroinflammatory markers alongside weight loss and glycemic improvements
- Gliburide (sulfonylurea): Effectively inhibits the NLRP3 inflammasome, suggesting potential for neuroinflammation-related disorders
- Sulfonylureas: Mouse studies showed anti-neuroinflammatory properties by targeting NLRP3 and modulating ERK/STAT3/NF-κB signaling
- Empagliflozin (SGLT2 inhibitor): Offered neuroprotection and helped neurovascular remodeling for cognitive function
- Insulin, metformin, thiazolidinediones: All have potential for repurposing against neuroinflammation
The shared pathway through NLRP3 inflammasome and IL-1β connects diabetes and neuroinflammation mechanistically.
Blossom, Vandana; Ullal, Sheetal D; Rai, Rajalakshmi; D Souza, Melisha Michael; Kalluraya, P Gopal Govind; Dixit, Ayush; Jiji, P J; Murlimanju, B V ·
RPEP-10183 · 2025Adding GLP-1 receptor agonists to standard PCOS therapy significantly outperformed standard therapy alone across multiple metabolic measures: body weight dropped by 3.44 kg more, BMI by 2.05 points, and waist circumference by 4.39 cm. The combination also improved insulin resistance (HOMA-IR reduced by 1.29) and fasting blood glucose.
Orlistat stood out for a different reason — it was the most effective at reducing testosterone levels (the key hormonal driver of PCOS symptoms) and raising HDL cholesterol. The overall conclusion supports combination pharmacotherapy for comprehensive PCOS management.
Bo, Yali; Zhao, Jie; Liu, Chengjiang; Yu, Ting · Meta Analysis
RPEP-10187 · 2025A 66-year-old woman developed rhabdomyolysis with markedly elevated creatine kinase levels following her first administration of an increased dose of tirzepatide. The temporal relationship between drug initiation and symptom onset strongly suggested tirzepatide as the trigger. Laboratory findings normalized within 4 days of drug discontinuation and supportive IV fluid therapy. The authors report this as the first documented case of rhabdomyolysis associated with tirzepatide.
Bodanowitz, Jonas Michael; Mattes, Isabell; Loebermann, Micha; Fritzsche, Carlos ·
RPEP-10192 · 2025Among 63,561 Veterans with type 2 diabetes and coronary artery disease across 84 VA medical centers (2015-2023), Black Veterans were 15% less likely to receive evidence-based GLP-1 receptor agonist prescriptions compared to White Veterans (adjusted OR 0.85, 95% CI 0.74-0.98, p=0.025).
No racial disparity was found for SGLT2 inhibitor prescribing (adjusted OR 0.96, 95% CI 0.89-1.04, p=0.32). However, overall uptake remained low for both drug classes: only 42% of eligible patients received SGLT2 inhibitors and 15% received GLP-1RAs by 2023, indicating widespread undertreatment regardless of race.
Bolden, Demetria M; Richardson, Vanessa; Salahuddin, Taufiq; Henderson, Kamal; Hess, Paul L; Raghavan, Sridharan; Saxon, David R; Ho, P Michael; Waldo, Stephen W; Schwartz, Gregory G ·
RPEP-10197 · 2025A novel peptide (PTR-CE1) isolated from the skin secretion of an Ecuadorian leaf frog lacked antimicrobial activity due to a kink in its alpha-helix structure. By engineering two analogs with complete α-helix conformations, researchers created potent antimicrobial agents. PTR-CE1a showed broad-spectrum activity against all tested microorganisms with MIC values of 3.02–12.06 μM and only 7.5% hemolytic activity at its effective concentration. Both analogs were active against ampicillin-resistant bacteria.
Bonilla-Jiménez, Stefanny; Espinosa de Los Monteros-Silva, Nina; Morán-Marcillo, Giovanna; Bermúdez-Puga, Sebastián; Terán-Valdez, Andrea; Almeida, José R; Proaño-Bolaños, Carolina ·
RPEP-10204 · 2025GIPR activation has antiemetic properties that counteract the nausea and vomiting caused by GLP-1R activation. In rats and shrews, GIPR agonism blocked emesis and reduced malaise behaviors triggered by GLP-1R activation, while still maintaining the benefits of reduced food intake, weight loss, and improved glucose tolerance.
At equipotent doses for weight loss, tirzepatide (a dual GLP-1R/GIPR agonist) produced significantly fewer gastrointestinal side effects than semaglutide (a GLP-1R-only agonist). This explains why tirzepatide can achieve greater weight loss than semaglutide while patients report fewer GI complaints.
Borner, Tito; Pataro, Allison M; Doebley, Sarah A; Furst, Charles D; White, Alex D; Gao, Serena X; Chow, Angela; Sanchez-Navarro, Marcos J; Ghidewon, Misgana Y; Halas, Julia G; Mohiby, Allaha Z; Willard, Francis S; Grill, Harvey J; Ai, Minrong; Samms, Ricardo J; Hayes, Matthew R; De Jonghe, Bart C · Animal
RPEP-10205 · 2025The combined 4GI-HbA1c systems model successfully predicted the glucose and HbA1c-lowering effects of both liraglutide (a GLP-1 agonist) and cotadutide (a dual GLP-1/glucagon agonist) using only in vitro potency data and pharmacokinetic information. The model was validated against continuous glucose monitoring data from Phase 2a studies and achieved prediction errors of 5.9% for fasting plasma glucose and 13% for HbA1c.
Critically, the model was used prospectively during cotadutide's clinical development to predict 26-week glucose and HbA1c outcomes of a Phase 2b study before the study was initiated — and retrospective analysis confirmed the predictions were adequate.
Bosch, Rolien; Petrone, Marcella; Arends, Rosalin; Sijbrands, Eric J G; Hoefman, Sven; Snelder, Nelleke ·
RPEP-10209 · 2025In propensity score-matched analyses of abdominoplasty patients:
- GLP-1RA use independently increased hypertrophic scarring risk (RR=1.79, 95% CI 1.37-2.35), confirmed in sensitivity analysis against DPP-4 inhibitors (RR=2.40)
- Prior bariatric surgery increased hematoma risk (RR=1.55, 95% CI 1.11-2.17) and seroma risk (RR=1.55, 95% CI 1.19-2.02), but lowered hypertrophic scarring (RR=0.74) and systemic infections (RR=0.78)
- Combined BS + GLP-1RA use increased wound dehiscence risk (RR=1.92, 95% CI 1.12-3.38) and constitutional symptoms (RR=1.69, 95% CI 1.16-2.46)
The scarring finding with GLP-1RAs was robust across multiple analyses.
Boukind, Adam; He, Kevin; Speller, Nicholas; Badran, Saif ·
RPEP-10210 · 2025Among 499 diabetic patients undergoing hip hemiarthroplasty for femoral neck fractures, GLP-1RA use (n=248) was not associated with increased risk of any measured outcome compared to non-GLP-1RA users (n=251). Specifically, there was no increase in medical complications at 30, 90, or 365 days; no increase in surgical site infection, implant complications, or revision surgery; no increase in aspiration pneumonitis; and no difference in hospital length of stay or readmissions. GLP-1RA use was associated with decreased 365-day in-hospital mortality/hospice discharge. After controlling for confounders, no adverse outcome was associated with GLP-1RA use (all P>0.05).
Box, McKenna W; Puga, Troy B; Werthmann, Neil J; Liu, Yingxian; Riehl, John T ·
RPEP-10218 · 2025Across 26 RCTs with 143,296 participants with T2DM and CKD:
- SGLT2 inhibitors ranked highest (by P-score) for: composite renal events (0.94), eGFR decline >40% or renal replacement therapy (0.99), MACE (0.93), and heart failure (1.00)
- GLP-1 RAs ranked highest for: myocardial infarction (0.87), macroalbuminuria (0.86), and stroke (0.83)
- Both SGLT2 inhibitors and GLP-1 RAs had equal P-scores (0.83) for reducing all-cause mortality
- DPP-4 inhibitors had limited benefits compared to either SGLT2 inhibitors or GLP-1 RAs across all outcomes
Bramlage, Peter; Vijayan, Anjaly; Varghese, Treesa P; Melepurakkal Sadanandan, Deepthy; Lanzinger, Stefanie; Rodriguez, Carmen Ferrero ·
RPEP-10219 · 2025Among 121 patients who had regained weight (median 9.7 kg, or 27.9% of total weight previously lost) or had suboptimal weight loss after bariatric surgery, adjuvant obesity medications produced a median 8.8% total body weight loss (IQR 5.7-14.1%) over a median follow-up of 9 months.
Semaglutide was the most commonly prescribed (52.8% of patients), followed by naltrexone/bupropion (28.1%) and liraglutide (19.1%). The medications were effective across all surgery types: sleeve gastrectomy (59.7%), one-anastomosis gastric bypass (11.8%), adjustable gastric banding (6.7%), and conversional procedures (21.8%). Adverse effects were minor and consistent with those seen in non-surgical clinical trial populations.
Brancatisano, Anthony; Ryan, Brendan ·
RPEP-10220 · 2025A 48-year-old man with hyperkalemic periodic paralysis (hyperPP) caused by a SCN4A sodium channel mutation experienced dramatic reversal of chronic myopathy after starting semaglutide for weight loss. Before treatment, he could not rise from a chair without help and had a very slow gait. Over the following year, his strength and quality of life returned to levels he hadn't experienced in decades. Previous treatments with acetazolamide and diclofenamide had been ineffective. The authors propose semaglutide acts on skeletal muscle through both insulin-dependent and insulin-independent mechanisms.
Brand, Kenneth; Landry, Daniel; Mulhern, Jeffrey; Braden, Gregory ·
RPEP-10223 · 2025In free-choice diet obese hamsters with MASH and heart failure:
Semaglutide effects:
- Transiently reduced food intake
- Significantly reduced fructose and alcohol consumption
- Significant body weight loss
- Lower HOMA-IR index (improved insulin resistance)
- Improved dyslipidemia (cholesterol problems)
- Improved heart failure with preserved ejection fraction (HFpEF)
- Reduced hepatic fat content only (not full MASH resolution)
Lanifibranor showed similar cardiometabolic benefits but was superior in the liver, significantly improving both MASH and alcohol-related liver disease (MetALD).
Both drugs' effects in hamsters matched what has been observed in human clinical trials, validating the animal model.
Briand, François; Dubroca, Caroline; Wettstein, Guillaume; Grasset, Estelle; Breyner, Natalia; Bigot, Claire; Assaly, Rana; Broqua, Pierre; Sulpice, Thierry ·
RPEP-10228 · 2025A case of acute mesenteric ischemia (loss of blood flow to the intestines) occurred in a patient taking tirzepatide, a dual GIP/GLP-1 receptor agonist used for type 2 diabetes. The authors propose this rare but serious adverse event may be related to tirzepatide's effects on gastrointestinal motility and vascular perfusion. The case report serves as a safety alert highlighting the need for careful patient selection and close monitoring, particularly as tirzepatide use expands outside formal clinical supervision.
Brooks, Shani; Nafees, Samraiz; Abdi, Khaled; Austin, Isobel; Mahmood, Balal; Bowden, Adam; Warren, Emily; Crossley, Alexander; Mehmood, Azhar; Birkett, Victoria ·
RPEP-10233 · 2025Among 4,901 patients (3,004 conversion RYGB, 1,897 GLP-1 RA) with prior sleeve gastrectomy, pre-intervention weights were identical between groups (242.8 vs. 242.3 lbs, p=0.993). In multivariate analysis adjusting for sex, baseline BMI, age, and race, conversion to RYGB was associated with 11% greater percentage total body weight loss compared to GLP-1 RA treatment at 3 years. Both groups showed similar improvements in HbA1c at all time points (p>0.05). The cRYGB group had higher baseline HbA1c (6.19 vs. 5.85, p significant).
Brown, Avery; Sergent, Helena; Vu, Alexander Hien; Liu, Helen; Fisher, Jason; Somoza, Eduardo; Mei, Tony; Lipman, Jeffrey; Park, Julia; Chui, Patricia; Saunders, John; Kurian, Marina; Tchokouani, Loic; Orandi, Babak; Ferzli, George; Chhabra, Karan; Ren-Fielding, Christine; Parikh, Manish; Jenkins, Megan ·
RPEP-10237 · 2025GLP-1 receptor agonists are FDA-approved for type 2 diabetes and cardiovascular risk reduction, with beneficial effects extending to obesity and related conditions. The article discusses both the physiologic mechanisms and the psychological effects of these medications, providing a clinical overview of their safety and effectiveness profile.
Browne-Bradwisch, Sarah A; Smith, Erin Murphy; Wilson-Mooney, Catherine; Donahue-Stathis, Courtney ·
RPEP-10239 · 2025The NRPS-like gene LYS2 (3,825 bp, encoding 1,274 amino acids) was identified as essential for cyclo(Pro-Val) biosynthesis in the marine probiotic yeast M. guilliermondii GXDK6. The encoded enzyme (Lys2p, an L-2-amino-hexanedioic acid reductase) utilizes a novel macrocyclization mechanism involving peptide N-terminal and C-terminal imines through nucleophilic reactions.
Overexpressing LYS2 increased cyclo(Pro-Val) production by 45.5%, while knocking out LYS2 completely eliminated synthesis — confirming it as the essential biosynthetic gene. This establishes a new metabolic regulatory pathway for cyclic peptide production in yeast.
Bu, Ru; Li, Zhenze; Qin, Qiyu; Bai, Huashan; Meng, Can; Wei, Ruihang; Chen, Xinglin; Wu, Shanguang; Kashif, Muhammad; He, Sheng; Jiang, Chengjian ·
RPEP-10242 · 2025Pfizer's oral GLP-1 drug danuglipron produced statistically significant weight loss in adults with obesity — ranging from 5.0% to 12.9% beyond placebo depending on dose — over 26 to 32 weeks. However, the trial was marred by very high dropout rates: only 39.3% of participants completed treatment, with approximately 38% discontinuing due to adverse events (primarily nausea and vomiting).
The weight loss was dose-dependent, with higher doses producing more weight loss but also more GI side effects. The drug was given twice daily at doses from 40 to 200 mg, escalated over 1, 2, or 4 weeks. While the efficacy signal was clear, the tolerability problem was worse than expected across all treatment groups.
Buckeridge, Clare; Cobain, Sonia; Bays, Harold E; Matsuoka, Osamu; Fukushima, Yasushi; Halstead, Patricia; Tsamandouras, Nikolaos; Sherry, Nicole; Gorman, Donal N; Saxena, Aditi R · Rct
RPEP-10248 · 2025GLP-1 receptor agonists are associated with a range of dermatologic effects — some harmful, some potentially beneficial. On the adverse side: injection-site reactions, immune-mediated responses including hypersensitivity, urticaria, and bullous pemphigoid (a blistering skin condition), facial fat loss dubbed "Ozempic face," and hair loss in the form of telogen effluvium linked to rapid weight loss.
On the potentially positive side, emerging evidence suggests GLP-1 drugs may enhance wound healing and could benefit inflammatory skin conditions like psoriasis. The review highlights that as GLP-1 use expands to millions of patients, dermatologic side effects are becoming an increasingly important clinical consideration.
Burke, Olivia M; Sa, Brianna; Cespedes, David Alvarez; Tosti, Antonella · Review
RPEP-10249 · 2025A 30-year-old woman with treatment-resistant cystic acne and PCOS experienced near-complete clearance of her cystic acne within 4 weeks of starting rimegepant (a CGRP receptor antagonist) for migraine management. Key details:
- Previous failed treatments: antibiotics and hormonal therapy
- Most affected area (chin) cleared almost entirely
- Both cosmetic and physical discomfort (painful lesions) resolved
- Acne did not recur, except for a minor episode during high stress
- The improvement was an unexpected secondary benefit of migraine treatment
The proposed mechanism involves CGRP's role in neurogenic inflammation and its effects on sebaceous gland activity, both of which contribute to acne pathology.
Burke, Olivia M; Cocores, Alexandra; Beer, Jacob; Keri, Jonette E ·
RPEP-10260 · 2025Liraglutide preserved endothelium-dependent vasodilation (acetylcholine responses) in ophthalmic arteries of septic mice while untreated septic mice showed significantly impaired responses. The protective effect was linked to reduced oxidative stress markers: both dihydroethidium staining and NOX2 antibody staining showed elevated oxidative stress in untreated septic arteries but not in liraglutide-treated ones. Importantly, endothelium-independent vasodilation (sodium nitroprusside) and vasoconstriction (phenylephrine) were unaffected across all groups, confirming the dysfunction was specifically endothelial.
Böhm, Elsa Wilma; Omran, Wael; Zadeh, Jenia Kouchek; Arad, Tschingis; Pfeiffer, Norbert; Patzak, Andreas; Oelze, Matthias; Daiber, Andreas; Helmstädter, Johanna; Steven, Sebastian; Gericke, Adrian ·
RPEP-10262 · 2025The review found no evidence for major qualitative sex differences in the therapeutic effects of clinically approved GLP-1 analogs — both men and women benefit from these drugs for obesity, diabetes, and cardiovascular disease. However, a growing body of literature identifies quantitative sex differences in the response to GLP-1 and its analogs, meaning the magnitude or specific mechanisms of action may differ between sexes.
Notably, there appears to be an interaction between GLP-1 therapeutics and estrogens, which could affect drug responses in women across different life stages. The review also addresses emerging data on GLP-1 analogs' effects on mood and reproductive function, where sex differences are particularly relevant.
Börchers, Stina; Skibicka, Karolina P ·
RPEP-10268 · 2025GEP12, administered at doses of 1.57 or 12.53 μg/kg intraperitoneally, reduced voluntary fentanyl self-administration (2.5 μg/kg IV) in both male and female rats and shifted the fentanyl dose-response curve downward. The drug also reduced fentanyl-seeking behavior during reinstatement after extinction — a model of relapse.
Using fiber photometry, the researchers demonstrated that GEP12 reduced fentanyl-evoked dopamine release in the nucleus accumbens, identifying a central mechanism for its anti-addiction effects. Importantly, the behaviorally effective doses did not alter food intake or produce malaise-like side effects, suggesting a therapeutic window exists.
Caffrey, Antonia; Lavecchia, Enzo; Chichura, Kylie S; Hayes, Matthew R; Doyle, Robert P; Schmidt, Heath D ·
RPEP-10270 · 2025In the largest real-world study of its kind — analyzing over 810,000 new semaglutide users across 14 databases — semaglutide showed no increased risk of proliferative diabetic retinopathy (PDR) or treatment-requiring diabetic eye disease compared to other GLP-1 drugs or non-GLP-1 diabetes medications.
Semaglutide's risk of PDR was similar to dulaglutide (HR 0.81), empagliflozin (HR 0.83), and sitagliptin (HR 0.83), and significantly lower than glipizide (HR 0.59, p=0.01). For treatment-requiring retinopathy/macular edema, semaglutide actually showed lower risk than dulaglutide (HR 0.53, p=0.02), sitagliptin (HR 0.46, p=0.008), and glipizide (HR 0.55, p=0.02).
These findings provide strong reassurance that the retinopathy signal seen in the earlier SUSTAIN 6 trial does not translate into increased real-world eye disease risk.
Cai, Cindy Xinji; Nishimura, Akihiko; Baxter, Sally; Goetz, Kerry; Hribar, Michelle; Toy, Brian; Barkmeier, Andrew; Wang, Sophia; Swaminathan, Swarup; Flowers, Alexis; Brown, Eric; Xu, Benjamin; Chen, John; Chen, Aiyin; Leng, Theodore; Boland, Michael; Alshammari, Thamir; Bu, Fan; Falconer, Thomas; Martin, Benjamin; Westlund, Erik; Mathioudakis, Nestoras; Zhang, Linying; Fan, Ruochong; Wilcox, Adam; Lai, Albert; Stocking, Jacqueline C; Xie, Yangyiran; Lee, Lok Hin; Dorr, David; Humes, Izabelle; McCoy, David; Adibuzzaman, Mohammad; Areaux, Raymond; Brash, James; Weiskopf, Nicole; Morgan-Cooper, Hannah; Desai, Priya; Tran, Diep; Rustam, Zainab; Zhu, Gina; Swerdel, Joel; Sena, Anthony; Nagy, Paul; Suchard, Marc; Schuemie, Martijn; Hripcsak, George; Ryan, Patrick · Retrospective Cohort
RPEP-10271 · 2025The review consolidates current knowledge on antimicrobial peptide hydrogels, highlighting that hydrogel encapsulation addresses the two main clinical barriers for AMPs: pH-dependent instability and enzymatic degradation in vivo.
A particular focus is placed on reactive oxygen species (ROS) modulation as a key therapeutic mechanism. The authors catalog applications across at least seven biomedical domains — antifungal therapy, wound healing, cancer treatment, bioimaging, nucleic acid delivery, immunomodulation, and surgical implants — demonstrating the versatility of the AMP-hydrogel platform.
Cai, Dingjun; Li, Canhong; Zhu, Taifu; Li, Ruiqi; Zhang, Mu; Li, Xiaoling; Liu, Yilong; Dai, Zhifei; Wan, Lei; Lu, Haibin ·
RPEP-10278 · 2025In PDAC patients, S1PR1 levels in intrapancreatic nerves were significantly higher in those experiencing cancer-associated pain versus those without pain. In a mouse orthotopic pancreatic cancer model:
• S1PR1 was upregulated in dorsal root ganglia (DRGs) and colocalized with neurons and satellite glial cells
• Intrathecal injection of S1PR1 antagonists W146 and FTY720 effectively alleviated pain hypersensitivity
• Both antagonists suppressed the upregulation of TRPV1 (a pain-sensing ion channel) and CGRP (calcitonin gene-related peptide, a key pain-signaling neuropeptide)
• FTY720 additionally demonstrated partial anti-tumor effects on pancreatic cancer progression
The finding that S1PR1 blockade suppresses CGRP connects this sphingolipid pathway to the same neuropeptide signaling axis targeted by migraine therapies (anti-CGRP antibodies).
Cai, Shen-Quan; Zhang, Yi-Xuan; Wang, Chun; Gao, Yu; Wang, Ting-Yu; Xu, Fang-Ning; Liu, Qing-Zheng; Yin, Jing; Zhang, Zhi-Jie; Zhang, Shu; Duan, Muan-Lin; Huang, Ying; Tao, Gao-Jian ·
RPEP-10280 · 2025Among 1,572 T2DM patients (945 liraglutide, 627 dulaglutide), there was no overall significant difference in MACE between the two drugs. However, liraglutide users showed a significant increase in MACE with worsening kidney function:
- eGFR 60–89: HR 1.401 (95% CI 0.663–2.958)
- eGFR <60: HR 4.078 (95% CI 1.111–14.971, P = 0.0079)
This trend was not observed with dulaglutide (P = 0.1906), suggesting dulaglutide may maintain cardiovascular protection across CKD stages while liraglutide's benefit diminishes with declining renal function.
Cai, Yu-Xuan; Liu, Feng-Hsuan; Sun, Jui-Hung; Lin, Chia-Hung ·
RPEP-10284 · 2025Using RNAscope technology, researchers mapped opioid receptor expression in reproductive hormone neurons of female mice and rats. In mice, kappa-opioid receptors (Oprk1) were the predominant type in arcuate nucleus kisspeptin neurons, and their expression decreased during proestrus (high estrogen) compared to metestrus (low estrogen). All three opioid receptor types (kappa, mu, delta) were expressed in GnRH neurons and rostral periventricular kisspeptin neurons. In rats, arcuate kisspeptin neurons showed the same kappa receptor cycling pattern but with equal expression of all three receptor types rather than kappa predominance. The findings implicate kappa-opioid receptors in the estrogen feedback control of LH secretion.
Campideli-Santana, Ana C; Coolen, Lique M; Lehman, Michael N; Szawka, Raphael E ·
RPEP-10290 · 2025A PCL-collagen peptide composite filament was successfully fabricated using a scalable, non-toxic solvent-assisted blending process on a desktop extrusion system. The collagen peptides enhanced tensile stiffness through intermolecular hydrogen bonding with PCL while maintaining the matrix's crystalline and thermal properties.
The composite was confirmed biocompatible and exhibited intrinsic bioactive capabilities from the collagen peptides. Degradation studies showed the PCL degradation rate could be tuned. Complex 3D scaffolds based on Triply Periodic Minimal Surfaces (TPMS) were successfully fabricated using standard fused filament fabrication printing, demonstrating practical applicability.
Cantella, Stefano; Badini, Silvia; Bollati, Carlotta; Madar Saheb, Mushtaq Alam; Viganò, Roberto; Lammi, Carmen; Pugliese, Raffaele; Graziosi, Serena ·
RPEP-10304 · 2025Among 18 lupus patients treated with GLP-1 receptor agonists from the NYU Lupus Cohort, only one mild-to-moderate flare occurred at 6–10 months, and no patients accumulated new SLE classification criteria during follow-up. The flare rate was within expected background rates for the disease.
BMI reductions were statistically significant: median BMI decreased by 3% at 1–4 months (P = 0.002) and by 13% at 6–10 months (P = 0.001). Notably, 9 of 18 patients (50%) were initially denied insurance coverage for their GLP-1RA prescription. Only 24 of 1,211 patients (2%) in the entire lupus cohort had received a GLP-1RA, suggesting significant underutilization.
Carlucci, Philip M; Cohen, Brooke; Saxena, Amit; Belmont, H Michael; Masson, Mala; Gold, Heather T; Buyon, Jill; Izmirly, Peter ·
RPEP-10306 · 2025All 86 participants reported at least one perceived benefit of tirzepatide during the SURMOUNT-4 open-label phase, with the most commonly mentioned being improved appetite control, increased energy, and improved clothing fit.
Despite gastrointestinal side effects being common, participants generally valued the efficacy of tirzepatide enough to tolerate them. The single-use injection pen device was rated as easy to use. Most participants expressed willingness to continue tirzepatide treatment. Participants reported wide-ranging life improvements beyond direct pharmacological effects, suggesting the drug's impact extends beyond weight loss alone.
Carmichael, Chloe; Jouravskaya, Irina; Collins, Elizabeth; Burns, Danielle; Poon, Jiat Ling; Kitchen, Helen; Mojdami, Donna; Murphy, Madhumita; Ahmad, Nadia; Kanu, Chisom ·
RPEP-10313 · 2025Before CGRP mAb treatment, 73.6% of patients experienced 12 or more monthly migraine headache days; after treatment, only 9.0% did. Conversely, patients with 0-7 monthly migraine days went from 4.5% to 79.7%.
Monthly sick leave of 4+ days dropped from 37.0% to 4.0%. Full-time work/study capacity improved from 47.7% to 76.1%. Median pain intensity decreased from 8.0/10 to 6.0/10. Among the 383 respondents, 78 (20.4%) were on galcanezumab, the newest reimbursed CGRP mAb in Finland, and this group had more prior CGRP mAb switches suggesting they were harder-to-treat cases. Quality of life scores (MSQoL) did not differ between new users (0-6 months) and persistent users (6+ months), suggesting benefits are sustained.
Casey, Caroline S; Pölkki, Mari; Suvanen, Elisa K; Iso-Mustajärvi, Ilona; Purmonen, Timo; Peltonen, Essi J; Appel, Camilla K; Patel, Niraj J; Von Arx, Lill-Brith ·
RPEP-10317 · 2025The review establishes that type 2 diabetes, MASLD, and cardiovascular disease form a clinical triad connected by shared pathophysiology including insulin resistance, chronic inflammation, oxidative stress, and endothelial dysfunction. Under-recognized factors like gut-derived metabolites and adipose tissue dysfunction contribute to disease progression.
SGLT2 inhibitors, GLP-1 receptor agonists, and tirzepatide are identified as cardioprotective agents with potential to address multiple components of this triad simultaneously. However, the review notes gaps in translating these therapies from clinical trials to routine hepatology and cardiology practice.
Caturano, Alfredo; Nilo, Davide; Lorenzo, Giovanni Di; Rocco, Maria; Tagliaferri, Giuseppina; Piacevole, Alessia; Donnarumma, Mariarosaria; Iadicicco, Ilaria; Moretto, Simona Maria; Acierno, Carlo; Sardu, Celestino; Russo, Vincenzo; Perrone, Marco Alfonso; Vetrano, Erica; Galiero, Raffaele; Marfella, Raffaele; Bonfrate, Leonilde; Rinaldi, Luca; Conte, Caterina; Sasso, Ferdinando Carlo ·
RPEP-10320 · 2025Endogenous opioid systems — including somatostatin, dynorphin, β-endorphin, methionine enkephalin, endocannabinoids, and anti-inflammatory cytokines — modulate neurogenic inflammation in the dental pulp triggered by orthodontic forces. This explains why most patients experience minimal pain during orthodontic treatment despite the release of pro-inflammatory neuropeptides (Substance P, CGRP, Neurokinin A). However, when severe orthodontic forces are applied, these endogenous control mechanisms may be overwhelmed, leading to asymptomatic irreversible pulpitis or pulp necrosis.
Caviedes-Bucheli, Javier; Rios-Osorio, Nestor; Ulate-Rodríguez, Esteban; Muñoz-Alvear, Hernan Dario; Gaviño-Orduña, José F; Ortolani-Seltenerich, P Sebastian; Gomez-Sosa, Jose F; Munoz, Hugo Roberto ·
RPEP-10332 · 2025LL-37 at 4 μM concentration enhanced rhinovirus-induced interferon-beta (IFNβ) expression in BEAS-2B human airway epithelial cells and reduced viral load. This enhancement did not involve upregulation of classical viral sensors (TLR3, MDA5, RIG-I). Instead, the effect was dependent on endosomal acidification (blocked by chloroquine) and critically required calcium — chelating calcium with EGTA abolished the response. LL-37 directly increased intracellular calcium concentration, and mimicking this calcium rise with the ionophore A23187 replicated the IFNβ enhancement, confirming that calcium is the key mediator.
Cerps, Samuel; Ramu, Sangeetha; Gidlöf, Olof; Menzel, Mandy; Swärd, Karl; Uller, Lena; Nilsson, Bengt-Olof ·
RPEP-10348 · 2025Perch hydrolysates contained 62.60% peptides with low molecular weight (≤1 kDa), with collagen composition at 1,183 mg/100g and branched-chain amino acids at 1,122 mg/100g. The peptide sequence FPSLVRGP, at 6.21% abundance, was identified as potentially antihypertensive.
In fibroblast models, the peptides accelerated wound healing by increasing secretion of procollagen I, fibronectin, and hyaluronan. In SD rats with wounds mimicking human injuries, orally administered perch hydrolysates (MW <2.3 kDa) accelerated wound healing through the combined action of collagen-forming amino acids, branched-chain amino acids, and matrikines (extracellular matrix-derived signaling peptides).
Chang, Jia-Feng; Hsieh, Chih-Yu; Chen, Ling-Ni; Lee, Mao-Hsiang; Ting, Yi-Han; Yang, Chi-Yu; Lin, Chih-Cheng ·
RPEP-10349 · 2025After simulated digestion and purification, peptides from all three legumes showed potent ACE-inhibitory activity. The IC50 values (concentration needed to block 50% of ACE activity) improved two- to nine-fold after gel-permeation chromatography purification, reaching approximately 85 µg/mL for lentil, 64 µg/mL for black soybean, and 93 µg/mL for black turtle bean.
A total of 210 peptides were sequenced from the small (<3 kDa) fractions, with chain lengths from 6 to 18 amino acids. Lentil had the shortest average peptide length at 7.7 amino acids. Overall, the bioactive peptides contributed more antioxidant capacity and ACE inhibition than the phenolic compounds in these legumes. Black turtle bean proteins required more heating to achieve comparable digestibility to lentil and soy proteins.
Chang, Sam K C; Zhang, Yan; Pechan, Tibor ·
RPEP-10350 · 2025Chronic semaglutide treatment in rats created a surprising split in behavior: while it reduced overall food consumption (both free food reward and regular chow), it actually increased the motivational value of limited food rewards and food-associated cues. Semaglutide-treated rats worked harder on a progressive ratio schedule to earn food and responded more for a food-paired cue during conditioned reinforcement testing.
Importantly, semaglutide did not alter the acquisition or expression of Pavlovian conditioned approach behavior itself. The dissociation — eating less overall but wanting food more intensely when it's limited — suggests semaglutide doesn't simply suppress all food motivation but rather reshapes the relationship between reward value and availability.
Chang, Stephen E; Turner, Christopher A; Pagán, Natalia Morales; Pereira, Daniela; Kleer, Sophia; Flagel, Shelly B · Animal Study
RPEP-10351 · 2025Researchers conducted the first comprehensive mapping of sugar modifications (glycosylation) on proteins in human tear fluid, with a focus on lacritin — a protein critical for tear production, immune defense, and antimicrobial activity. They identified 19 specific sites where sugar chains attach to lacritin, and found that these glycans make up over 50% of the protein's molecular weight and make its structure rigid and extended.
Using AlphaFold 3.0 modeling, they visualized how these sugar modifications shape the protein's 3D structure. They also discovered two previously undetected splice variants of lacritin and characterized the glycosylation of other tear proteins including immunoglobulin A (IgA) and lactoferrin — both of which have antimicrobial properties and serve as disease biomarkers.
Chang, Vincent; Mahoney, Keira E; Lian, Isaac; Chen, Ryan; Chung, Nara; Paaske Utheim, Tor; Karlsson, Niclas G; Malaker, Stacy A · Basic Science (Analytical/Proteomics)
RPEP-10361 · 2025The review identified three categories of AT1R antagonists investigated from 2020 to 2024: large peptide molecules, small non-peptide-like molecules, and sartan derivatives. Notably, some non-sartan compounds exhibited very low IC50 values (indicating high potency), demonstrating that there is substantial chemical space beyond current drug classes that could yield more effective antihypertensive medications.
Computational chemistry analysis revealed the key molecular interactions governing binding affinity at the AT1R active site, explaining why structurally diverse compounds show different potencies. The review also updated understanding of AT1R structure-function relationships based on recent cryo-EM and crystallographic data.
Chatzipieris, Filippos Panteleimon; Petsas, Errikos; Lambrinidis, George; Matsoukas, John M; Mavromoustakos, Thomas ·