RPEP-12672 · 2025A 55-year-old African American female with a history of deceased donor renal transplantation developed:
• Extensive thrombosis of the left AV fistula
• Thrombosis extending to the brachiocephalic vein
• Thrombosis of both radial and ulnar arteries
• Symptoms: pain, swelling, erythema, fever, chills, and loss of palpable thrill over the fistula for approximately one week
Comprehensive prothrombotic workup (both inherited and acquired hypercoagulable states) was completely unremarkable. The only identifiable change was a recent dose escalation of her GLP-1 receptor agonist. After the drug was discontinued, no further thrombotic events occurred during follow-up, supporting a temporal and causal association.
Muneeb, Muhammad; Choi, Elizabeth; Rodriguez, Coralys; Goyal, Kanika; Bhura, Zainab; Hannoudi, Ghadeer ·
RPEP-12675 · 202518F-exendin-4 PET/CT achieved 100% sensitivity for insulinoma detection in 12 patients, significantly outperforming CT (83%), MRI (63%), endoscopic ultrasonography (90%), and selective arterial calcium stimulation (89%). The peptide-based probe showed significantly higher uptake in tumor tissue than surrounding pancreatic tissue. All 12 lesions were surgically confirmed as insulinomas, and all patients achieved complete resolution of hypoglycemia after resection.
Murakami, Takaaki; Yoshida, Hayao; Sakaki, Kentaro; Otani, Daisuke; Kawai Miyake, Kanae; Shimizu, Yoichi; Fujimoto, Hiroyuki; Yabe, Daisuke; Nakamoto, Yuji; Inagaki, Nobuya ·
RPEP-12677 · 2025Among 25 patients who took weekly semaglutide less than 7 days before surgery:
- 20 patients (80%) had empty stomachs on ultrasound and proceeded without complications
- 5 patients (20%) had residual gastric contents despite adequate NPO (fasting) status and were rescheduled
- Semaglutide taken 1-3 days before surgery was significantly associated with residual gastric contents compared to 4-6 days before (p = 0.02)
- No postoperative aspiration complications occurred in patients who proceeded after clear ultrasound
Muranaka, Mehana O; Nguyen, Tony H; Wang, Annie T; Cordero, Justin; Yang, Su-Jau; Felix, Jasmine; Nguyen, Jennifer L; Carré, Antoine L; Chu, Michael W ·
RPEP-12689 · 2025Snake venoms contain a diverse arsenal of bioactive peptides and proteins that kill bacteria through multiple mechanisms: punching holes in cell membranes, enzymatically degrading microbial structures, generating oxidative stress, breaking up biofilms, and modulating the immune system. These compounds show broad-spectrum activity against drug-resistant bacteria in lab settings.
The review also highlights a newer discovery — snake venom-derived extracellular vesicles (SVEVs) — tiny membrane-bound packages that protect venom compounds from degradation and improve their delivery to target sites. Advanced delivery strategies including PEGylation, liposomes, hydrogels, microneedle patches, and nanoparticles are being developed to reduce the toxicity of these venom compounds while preserving their antimicrobial potency.
Muttiah, Barathan; Hanafiah, Alfizah · Review
RPEP-12693 · 2025In a propensity-matched retrospective study of 20,959 patients per group, GLP-1 receptor agonists were associated with a significantly lower hazard of nonexudative AMD (HR 0.47, 95% CI 0.28–0.78) and any AMD (HR 0.61, 95% CI 0.43–0.85) compared to other weight loss pharmacotherapies.
The difference for exudative (wet) AMD alone was not statistically significant (HR 0.63, 95% CI 0.30–1.32). Importantly, BMI and hemoglobin A1c trajectories were similar between the two groups over follow-up, suggesting the protective association is not simply driven by greater weight loss or metabolic improvement.
Myers, Walter K; Heath, Garrett; Rohrer, Bärbel ·
RPEP-12694 · 2025Cerebiome probiotic attenuated increased calorie intake in Western-diet-fed rats. Probiotic standard-diet males showed reduced anxiety in the novelty-suppressed feeding task. Probiotic rats overall had more feeding bouts in the center of the open field (suggesting less anxiety about eating in a novel environment). Probiotic administration increased adrenal neuropeptide Y (NPY) expression regardless of diet or sex. Plasma leptin was increased with Western diet; plasma ghrelin was elevated in standard-diet females. Female rats had higher adrenal glucocorticoid receptor expression than males. Effects were sex- and diet-dependent, highlighting the importance of studying both variables.
Myles, Elizabeth M; O'Leary, M Elizabeth; Romkey, Isaac D; Hamm, Sara I; Dauphinee, Laura; Piano, Amanda; Bronner, Stéphane; Perrot, Tara S ·
RPEP-12695 · 2025Across all 23 RCTs (n=1,474), collagen supplements appeared to significantly improve skin hydration, elasticity, and wrinkles. However, subgroup analysis by funding source revealed that only pharmaceutical/supplement company-funded studies showed significant effects — independently funded studies showed no benefit in any category. Similarly, high-quality studies showed no significant effect across all skin measures, while low-quality studies showed improvement only in elasticity. The authors concluded there is no clinical evidence to support collagen supplements for skin aging.
Myung, Seung-Kwon; Park, Yunseo ·
RPEP-12701 · 2025Obesity pathophysiology involves insulin resistance, dyslipidemia, chronic low-grade inflammation, and neuroendocrine dysregulation of appetite. Gut-derived peptide hormones (leptin, ghrelin, GLP-1, PYY, CCK) are pivotal regulators of appetite and weight. Beyond caloric excess, genetic predisposition, epigenetic modifications, gut microbiota dysbiosis, endocrine-disrupting chemicals, circadian misalignment, and prenatal/intergenerational influences are all critical determinants. Advances in molecular profiling and metabolic phenotyping are enabling precise risk stratification and personalized treatment selection.
Młynarska, Ewelina; Bojdo, Kinga; Bulicz, Anna; Frankenstein, Hanna; Gąsior, Magdalena; Kustosik, Natalia; Rysz, Jacek; Franczyk, Beata ·
RPEP-12702 · 2025In 10 pediatric chronic migraine patients who had failed at least 2 prior preventive therapies, CGRP monoclonal antibodies or antagonists combined with structured lifestyle modifications produced significant improvements over 12 months:
- Migraine frequency decreased from a median of 26.5 to 14 days per month (statistically significant)
- Acute analgesic use dropped from 14 to 5 days per month (statistically significant)
- Disability scores improved significantly (p=0.037)
All patients had severe baseline burden (PedMIDAS score ≥30, ≥8 migraine days per month), making these reductions clinically meaningful for this difficult-to-treat population.
Na, Ji-Hoon; Jeon, Hayoon; Shim, Ji-Eun; Lee, Hyunjoo; Lee, Young-Mock ·
RPEP-12703 · 2025The review reached several key conclusions about GLP-1 receptor agonists and eye health:
1. Preclinical studies hint at possible retinal protective effects of GLP-1 agonists
2. Clinical cases of retinopathy worsening after GLP-1RA use are likely due to rapid reduction in glycated hemoglobin (HbA1c) levels rather than the drug's mechanism of action — a phenomenon known as 'early worsening' that occurs with any treatment that rapidly improves blood sugar control
3. Evidence linking semaglutide specifically to nonarteritic anterior ischemic optic neuropathy (NAION) remains inconclusive and limited by methodological constraints
4. Large-scale, well-designed studies are needed to clarify both potential associations and guide clinical practice
Nadeem, Nadia; Al Issa, Raghad Mazin; Shah, Asnin; Wardeh, Rahaf; Rashid, Fauzia; Abdelgadir, Elamin Ibrahim; Bashier, Alaaeldin ·
RPEP-12705 · 2025NeoPAIR-T successfully identified two functional neoantigen-TCR pairs from lung cancer samples out of 63 candidate peptides and 8 TCR clonotypes. The system uses CRISPR-engineered Jurkat reporter T cells with luciferase/eGFP dual readout and autologous antigen-presenting cells transfected with tandem minigenes encoding predicted neoantigens. The validated pairs showed functional binding with EC50 values ranging from 10⁻⁹·² to 10⁻⁶·⁷ M, confirmed by peptide assays. Key innovations include TCRα-knockout with targeted knock-in to prevent receptor mispairing, and the ability to test multiple reporter clones in parallel against the same antigen-presenting cells.
Nagaoka, Koji; Kobayashi, Yukari; Kakimi, Kazuhiro ·
RPEP-12707 · 2025A 63-year-old woman with grade II obesity (BMI not specified but >35 kg/m²) was initially denied as a living kidney donor. After 3 months of comprehensive treatment at a cardio-obesitology clinic — including caloric restriction, physical activity, and liraglutide — her BMI decreased to 33.4 kg/m². Subsequent evaluation confirmed no surgical contraindications. An incidental finding of hematuria led to a diagnosis of benign Alport syndrome carrier status, which without proteinuria or renal impairment did not preclude donation. She successfully donated her kidney.
Nagy, Norbert; Kleinová, Patrícia; Péč, Martin Jozef; Samoš, Matej; Dedinská, Ivana ·
RPEP-12713 · 2025Novel NPY::Venus transgenic mice were successfully generated, allowing direct visualization of neuropeptide Y secretory granules in brain tissue using confocal and super-resolution microscopy. The key finding was that the number of NPY secretory granules released onto the SCN increased during fasting conditions, providing direct visual evidence that NPY serves as a feeding-state signal to the brain's master circadian oscillator.
This establishes that NPY from the intergeniculate leaflet (IGL) neurons is actively secreted onto the SCN in response to fasting, suggesting a mechanism by which the food-entrainable oscillator communicates with the light-dependent circadian clock.
Nakazawa, Kazuo; Matsuo, Minako; Nakao, Kazuki; Nonaka, Shigenori; Numano, Rika ·
RPEP-12715 · 2025Over a median follow-up of 27 weeks, adding finerenone to existing SGLT2 inhibitor and GLP-1 receptor agonist therapy produced an adjusted 51.3% reduction in urinary albumin-to-creatinine ratio (UACR), a key marker of kidney damage.
Kidney function (eGFR) remained stable during the treatment period. Serum potassium levels did not rise to dangerous levels. The albuminuria reduction was consistent across subgroups analyzed by age, sex, BMI, baseline eGFR, and baseline UACR.
Notably, 94% of patients were also receiving a renin-angiotensin system inhibitor, meaning this was effectively a quadruple-therapy approach targeting multiple pathways of diabetic kidney disease.
Nakhleh, Afif; Khazim, Khaled; Shehadeh, Naim ·
RPEP-12732 · 2025In type 2 diabetes patients, GLP-1 RA treatment was associated with significantly lower incidences of multiple systemic conditions compared to non-users (over 5+ years of follow-up):
- Dementia: Risk Difference -0.010 (p<0.001)
- Alzheimer's disease: RD -0.003 (p<0.001)
- Parkinson's disease: RD -0.002 (p<0.001)
- Pancreatic cancer: RD -0.003 (p<0.001)
- Systemic lupus erythematosus: RD -0.001 (p<0.001)
- Systemic sclerosis: RD -0.000 (p<0.001)
Bronchial asthma showed a slight increase in risk (RD 0.002, p<0.001). Similar patterns were observed in the obesity-only cohort. Additional conditions evaluated included rheumatoid arthritis, ulcerative colitis, Crohn's disease, osteoporosis, and several cancers.
Nassar, Mahmoud; Nassar, Omar; Abosheaishaa, Hazem; Misra, Anoop ·
RPEP-12736 · 2025Across 78 randomized clinical trials with 73,640 participants, semaglutide showed no association with increased risk of eye disorders overall (OR 1.01; 95% CI 0.91–1.12) or diabetic retinopathy specifically (OR 1.04; 95% CI 0.92–1.17).
However, semaglutide treatment was associated with significantly increased odds of nonarteritic anterior ischemic optic neuropathy (NAION), with an OR of 3.92 (95% CI 1.02–15.02). This is a rare but serious condition involving sudden loss of blood flow to the optic nerve.
Trial sequential analysis confirmed sufficient sample size to rule out increased diabetic retinopathy risk, but the data were insufficient to draw definitive conclusions about the NAION association, given the rarity of this event.
Natividade, Gabriella R; Spiazzi, Bernardo F; Baumgarten, Matheus W; Bassotto, Caroline; Pereira, Afonso A; Fraga, Bruna L; Scalco, Bruno G; Mattes, Nicole R; Lavinsky, Daniel; Kramer, Caroline K; Gerchman, Fernando ·
RPEP-12740 · 2025Of 23 obese kidney transplant candidates initially rejected due to obesity, semaglutide treatment (up to 1 mg/week subcutaneously) over a median of 12.2 months produced significant improvements: mean weight decreased by 11.4 kg (p ≤ 0.001), BMI dropped by 3.9 points (p ≤ 0.001), and waist circumference decreased by 9.6 cm (p ≤ 0.001).
56.5% of patients (13 of 23) who had been rejected for transplantation were subsequently listed within a median of 5.4 months. Of those listed, 61.5% (8 patients) were successfully transplanted. No major side effects were reported during the treatment period. Starting weight, BMI, and waist circumference averaged 102.9 kg, 35.6, and 119.5 cm respectively.
Navaux, Emilie; La, Caroline; Dufour, Sylvain; Huberty, Vincent; Mourabit, Youssef; Caes, Thomas; Koliakos, Nikolaos; Mikhalski, Dimitri; Le Moine, Alain; Catalano, Concetta ·
RPEP-12750 · 2025Among 21,247 adults with type 2 diabetes using semaglutide, the 2,759 who also used CGM achieved significantly greater HbA1c improvements than the 18,488 using semaglutide alone (difference-in-differences: -0.55%, 95% CI: -0.64% to -0.47%, p < 0.0001).
Among CGM users, the proportion meeting the ADA target of HbA1c < 7.0% nearly doubled, and the proportion achieving the HEDIS target of HbA1c < 8.0% increased by more than 50%. These results suggest that CGM provides an additive benefit beyond the pharmacological effect of semaglutide alone.
Nemlekar, Poorva M; Hannah, Katia L; Green, Courtney R; Grace, Thomas; Lynch, Peter M; Castle, Jessica R; Norman, Gregory J ·
RPEP-12751 · 2025Among over 52,000 adults with type 2 diabetes not using insulin, adding continuous glucose monitoring (CGM) was associated with a 0.45% greater HbA1c reduction compared to not using CGM (p<0.0001). The benefit of CGM was particularly pronounced when combined with GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas — these medications showed statistically significant interaction effects, meaning CGM amplified their glucose-lowering benefits more than it did for metformin or SGLT2 inhibitors.
Nemlekar, Poorva M; Hannah, Katia L; Green, Courtney R; Norman, Gregory J · Observational
RPEP-12753 · 2025Lower consumption of unprocessed foods was associated with significantly higher ghrelin concentrations (p=0.023), greater body fat percentage (p=0.047), and reduced lean mass percentage (p=0.047). Agouti-related peptide (AgRP) was a positive predictor of ultraprocessed food consumption (β=0.30, p=0.04), independent of age, body fat, and binge eating symptoms. Six appetite-regulating peptides were measured: ghrelin, leptin, neuropeptide Y, AgRP, melanin-concentrating hormone, and α-MSH.
Neres, Patrícia Sousa; Ganen, Aline de Piano; Campos, Raquel Munhoz da Silveira; Carvalho Ferreira, Joana Pereira de; Oyama, Lila Missae; Dâmaso, Ana Raimunda; Masquio, Deborah Cristina Landi ·
RPEP-12758 · 2025Three anti-migraine drugs that target the CGRP pathway — ubrogepant, erenumab, and eptinezumab — also reduce the force of heart contraction in isolated human atrial tissue at therapeutic concentrations. CGRP (calcitonin gene-related peptide), a key migraine peptide, also increases heart contraction force in human atrial tissue at nanomolar concentrations. All three anti-migraine drugs blocked this cardiac effect of CGRP, both when applied before and after CGRP.
The finding raises an important safety question: since CGRP plays a role in heart function, do anti-migraine drugs that block CGRP also affect the heart in living patients?
Neumann, Joachim; Hofmann, Britt; Gergs, Ulrich · Ex Vivo
RPEP-12760 · 2025The WRAP5 cell-penetrating peptide functionalized with a transferrin receptor ligand (Tf) successfully co-delivered temozolomide and a p53-encoding plasmid to U87 glioma cells. Computational modeling of circadian gene expression revealed key timing windows: the transferrin receptor expression peaked at T7 and T8 time points, while clock genes Bmal1 and Per2 peaked at T16 and T8, respectively.
Confocal microscopy confirmed that intracellular uptake of the peptide nanocomplexes and p53 mRNA expression were highest at T8 — the time point coinciding with peak transferrin receptor and Per2 expression. Protein-level analysis confirmed these transcriptional changes, with T16 emerging as a favorable time point for maximizing therapeutic efficacy. The results demonstrate that synchronizing peptide nanocomplex delivery with tumor circadian biology can enhance both cellular uptake and therapeutic gene expression.
Neves, Ana R; Vivès, Eric; Boisguérin, Prisca; Quintela, Telma; Costa, Diana ·
RPEP-12762 · 2025All three doses of tirzepatide (5, 10, and 15 mg) outperformed semaglutide 1 mg in helping patients achieve multiple standard and intensive therapeutic targets simultaneously at 40 weeks.
For standard targets, 57% of patients on tirzepatide 15 mg met three or more goals versus 34% on semaglutide. For intensive targets, the gap was even wider: 29% on tirzepatide 15 mg versus 8% on semaglutide achieved three or more goals.
Tirzepatide significantly increased the odds of achieving both standard and intensive weight loss targets (>10% weight loss: OR 2.72; >15% weight loss: OR 3.86) and intensive blood pressure targets (OR 1.45). Tirzepatide also improved HbA1c target attainment across both standard and intensive thresholds.
Neves, João Sérgio; Leite, Ana Rita; Vale, Catarina; Marques, Pedro; Vasques-Nóvoa, Francisco; Leite-Moreira, Adelino; Ferreira, João Pedro ·
RPEP-12765 · 2025Multiple peptide-based therapies are showing substantial promise for treating MASH (metabolic dysfunction-associated steatohepatitis), the progressive form of fatty liver disease. GLP-1 agonists (semaglutide), dual agonists (tirzepatide, survodutide), and triple agonists are among the most advanced candidates. Recent trials demonstrate these drugs can resolve liver inflammation and improve fibrosis — the two key histological endpoints.
Other promising approaches include PPAR agonists (lanifibranor), FGF21 analogs (pegozafermin), THR-β agonists (resmetirom, the first FDA-approved MASH drug), and fatty acid synthase inhibitors. The field is moving toward combination therapies and precision medicine approaches using genetic variants like PNPLA3 to guide treatment selection.
Newsome, Philip N; Loomba, Rohit · Review
RPEP-12767 · 2025Among 3,452 semaglutide users matched against 15,486 controls undergoing single-level lumbar fusion, semaglutide use was associated with significantly lower 90-day readmission rates (8.7% vs. 11.4%) and lower 90-day costs. No significant differences were found in rates of stroke, heart attack, blood clots, pneumonia, low blood sugar, or surgical site infections.
The study suggests semaglutide provides perioperative benefits for spine surgery patients with diabetes without increasing complication risk.
Ng, Mitchell K; Mastrokostas, Paul G; Rodriguez, Ariel N; Razi, Abigail; Mastrokostas, Leonidas E; Emara, Ahmed K; Ford, Brian T; Xu, Jacquelyn J; Dalton, Jonathan; Narayanan, Rajkishen; Kepler, Christopher K; Hilibrand, Alan S; Vaccaro, Alexander R; Monsef, Jad Bou; Razi, Afshin E ·
RPEP-12780 · 2025Both semaglutide and tirzepatide perform comparably at the FDA's 5% body weight loss threshold. However, tirzepatide significantly outperforms semaglutide as the weight loss target increases from 5% to 20%, with fewer participants failing to reach higher thresholds.
Tirzepatide showed particularly strong effects in people with type 2 diabetes compared to semaglutide. The analysis also revealed significant disparities in trial participation by race and geographic region across all 10,407 studies reviewed. Critically, the researchers found that the specific effects of weight loss therapies on the kidneys, heart, different muscle types, bones, and regional fat distribution were rarely investigated or reported during clinical trial periods or longer-term monitoring.
Nguyen, Trung Tin; Elmaleh, David R ·
RPEP-12782 · 2025Long-term studies published in 2023-2024 confirm ongoing safety and efficacy for all four CGRP-targeting monoclonal antibodies in episodic migraine prevention. These therapies reduce monthly migraine days and increase quality of life while being better tolerated than non-specific migraine preventive therapies (such as beta-blockers, antidepressants, and anticonvulsants).
The accumulated evidence has led to the 2024 American Headache Society (AHS) consensus statement recommending CGRP monoclonal antibodies be considered as first-line preventive treatment in episodic migraine — a significant elevation in their clinical positioning.
Nicol, Kelly S; Burkett, John G ·
RPEP-12783 · 2025A 29-year-old woman with PCOS and IIH without papilledema (IIHWOP) was treated with exenatide after intolerance to acetazolamide. Key findings:
- Headache frequency and diplopia (double vision) improved early, independent of weight loss, suggesting direct receptor-mediated reduction of cerebrospinal fluid secretion and intracranial pressure
- Menstrual cycles and hormonal profile improved beyond the effects of metformin alone
- Insulin resistance improved
- The patient had gained 15 kg over eight months prior to treatment
- IIH was diagnosed by MRI (enlarged pituitary fossa, partial empty sella, optic nerve sheath dilatation) and lumbar puncture showing raised opening pressure of 280 mmH₂O with normal CSF composition
Nicolaou, Despina; Nicolaou, Nicolas; Douglas, Lisa M; Christou, Savvas ·
RPEP-12788 · 2025Across 19 studies and 1,290 patients with suboptimal initial response or weight regain after bariatric surgery, GLP-1 receptor agonists produced the following results after at least 3 months:
• Tirzepatide: 15.50% total weight loss (TWL), 12.60 kg
• Semaglutide: 11.38% TWL, 11.62 kg
• Liraglutide: 9.24% TWL, 8.56 kg
Longer treatment duration improved outcomes: semaglutide at 12 months achieved 13.15% TWL and 14.68 kg loss, compared to 10.18% TWL and 9.43 kg at 6 months. Liraglutide showed similar time-dependent gains (10.80% TWL at ≥12 months vs 7.65% at ≤6 months).
Significant improvements were also seen in triglycerides, total cholesterol, LDL cholesterol, HbA1c, and ALT levels. Common adverse effects included nausea (23%), constipation (10%), fatigue (8%), vomiting (6%), diarrhea (6%), and headache (6%), with only 3% discontinuing due to side effects.
Nie, Yuntao; Zhang, Yiran; Liu, Baoyin; Meng, Hua ·
RPEP-12792 · 2025In 43 randomized patients (23 ESG, 20 liraglutide) with class I-II obesity:
• At 3 and 6 months: ESG significantly outperformed liraglutide for both %EWL and %TWL (P=0.001)
• At 12 months: No statistically significant difference between groups — the ESG advantage had disappeared
• ESG pattern: rapid initial weight loss followed by some weight regain after 6 months
• Liraglutide pattern: slower but more consistent weight loss that continued beyond 6 months
• Resolution of obesity-related comorbidities: no significant differences between groups at any time point (3, 6, or 12 months)
• Safety: no major complications or significant side effects in either group
Nigro, Stefania; Vinciguerra, Federica; Guccione, Fabio; Alibrandi, Angela; Filannino, Ruggiero; Navarra, Giuseppe ·
RPEP-12794 · 2025A 37-year-old woman with normal BMI developed subocclusive ileus (functional intestinal obstruction) following unsupervised, off-label use of semaglutide for cosmetic weight loss purposes.
Nikolaeva, Arina; Vandeputte, Martin ·
RPEP-12802 · 2025In 54 heart failure patients treated with sacubitril/valsartan over 12 weeks:
- Total BNP and BNPcom (commercial assay) did not change overall
- NT-proBNP and proBNP decreased (reflecting hemodynamic improvement)
- Mature BNP modestly increased (because neprilysin inhibition prevents its degradation)
- ANP (A-type natriuretic peptide) greatly increased
Responders (n=31, defined by NT-proBNP <70% of baseline at 12 weeks) showed smaller percentage changes in all natriuretic peptides than non-responders (n=23; all P<0.01). The percentage change in each natriuretic peptide at 4 weeks predicted responder status with AUC of approximately 0.80. Correlations between peptide levels at baseline and during treatment were strong and consistent.
Nishikimi, Toshio; Nakagawa, Yasuaki; Miyamoto, Shoichi; Kanamori, Takahiko; Inazumi, Hideaki; Yanagisawa, Hiromu; Moriuchi, Kenji; Kinoshita, Hideaki; Tamamura, Yusuke; Takahama, Hiroyuki; Minamino, Naoto; Ono, Koh ·
RPEP-12807 · 2025In 32 mice divided into four groups (control, high-fat, semaglutide, empagliflozin), both semaglutide and empagliflozin significantly improved glycolipid metabolism, reduced inflammation and oxidative stress, and restored pathological liver structure compared to the high-fat group. No statistically significant differences were found between the two drugs for MASLD outcomes.
Metabolomics revealed that both drugs reduced levels of several lysophosphatidylcholine (LPC) species in liver tissue, suggesting the liver-protective effects may be mediated through LPC modulation.
Niu, Shu; Chen, Shu-Chun; Wang, Chen-Xi; Yue, Lin; Wang, Shu-Qi ·
RPEP-12812 · 2025Monthly headache days decreased significantly from 22.0 to 11.5 days (p=0.002) during concurrent treatment with anti-CGRP monoclonal antibodies and MS disease-modifying therapies.
MS disability scores (EDSS) remained stable at 1.9 throughout the study period — from the year before starting anti-CGRP treatment through the last follow-up. Only two patients (8%) experienced a clinical MS relapse and one (4%) showed MRI activity during the treatment period. Mild adverse events occurred in just two patients (8%), and none led to discontinuation of the anti-CGRP therapy.
Nociti, Viviana; Romozzi, Marina; Annovazzi, Pietro; Fantozzi, Roberta; Tortorella, Carla; Vercellino, Marco; Iannone, Luigi Francesco; De Luca, Giovanna; Tomassini, Valentina; Di Filippo, Massimiliano; Lorefice, Lorena; Maniscalco, Giorgia Teresa; Paolicelli, Damiano; Pinardi, Federica; Ronzoni, Marco; Solaro, Claudio Marcello; Gasperini, Claudio; Calabresi, Paolo; Vollono, Catello; Cocco, Eleonora ·
RPEP-12813 · 2025From 869 trials with 493,168 participants covering 63 drugs across 13 classes:
Weight loss leaders: tirzepatide (-8.63 kg, moderate certainty) and orforglipron (-7.87 kg, low certainty), followed by 8 other GLP-1 RAs (high to moderate certainty).
Cardiovascular/kidney benefits: SGLT-2 inhibitors, GLP-1 RAs, and finerenone confirmed with moderate to high certainty evidence.
Key harms: tirzepatide and GLP-1 RAs probably increase severe gastrointestinal events (tirzepatide OR 4.21, moderate certainty). SGLT-2 inhibitors increase genital infections (OR 3.29) and ketoacidosis (OR 2.08). Sulfonylureas and insulin increase hypoglycemia.
Uncertainty remains about whether GLP-1 RAs reduce dementia (OR 0.92, low certainty) and effects on neuropathy and visual impairment.
Nong, Kailei; Jeppesen, Britta Tendal; Shi, Qingyang; Agoritsas, Thomas; Guyatt, Gordon H; White, Heath; Gao, Yiyuan; Agarwal, Arnav; Macdonald, Helen; Zou, Xinyu; Millard, Tanya; Schnell, Oliver; Marx, Nikolaus; Brosius, Frank C; McDonald, Steve; Quigley, Matthew; Tian, Xin; Fan, Qinlin; White, Barbara; Mao, Yunhe; Pan, Xiaohui; Liu, Changhai; Zhai, Chunjuan; Yuan, Chi; Li, Qiang; An, Jing; Gan, Yu; Wang, Yanyan; Jin, Yinghui; Sun, Feng; Zhu, Zhiming; Rydén, Lars; Standl, Eberhard; Turner, Tari; Vandvik, Per Olav; Li, Sheyu ·
RPEP-12815 · 2025In a real-world Swiss clinic, 22 adolescents with obesity treated with liraglutide (Saxenda) showed significant BMI reduction comparable to clinical trial results. BMI-SDS dropped from +2.63 to +2.40 (median reduction -0.20, p=0.0003) with a large effect size (rb = -0.77).
However, 13 of 22 patients (59%) discontinued treatment — mainly due to insufficient weight loss or mild nausea. Among the 9 who continued, results were more impressive: BMI-SDS dropped from +2.59 to +2.08. No serious adverse events occurred. The mean treatment duration was only 8.2 months, and 15 of 22 patients had Southern European immigrant backgrounds.
Noordam, Cees; Eiholzer, Urs; Katschnig, Claudia; Stasinaki, Aikaterini; Dubinski, Ilja · Observational
RPEP-12818 · 2025From a dataset representing over 161 million US patients, 92,405 semaglutide users and 16,082 sleeve gastrectomy patients were identified. After high-dimensional propensity score matching, 2,887 individuals were compared in each group. Over a mean follow-up of 3 years, the semaglutide group had 86 fractures (2.98%) versus 128 fractures (4.43%) in the surgery group.
This translated to a hazard ratio of 0.74 (95% CI: 0.56-0.98), meaning semaglutide users had a statistically significant 26% lower fracture risk. Both groups were well-matched: mean age 45, predominantly female (~78%), similar comorbidity burden (Charlson Index 1.9), and similar racial composition.
Noreña, Jairo A; Pike, C William; Hui, Gavin; Motlaghzadeh, Yasaman; Sellmeyer, Deborah E; Wu, Joy Y; Kim, Sun H ·
RPEP-12819 · 2025Combining low-dose zalfermin (an FGF21 analog) with low-dose semaglutide produced super-additive weight loss of 18% in MASH mice — far exceeding either drug alone at the same doses (zalfermin -6%, semaglutide -4%). The combination was equally effective as high doses of either drug given alone.
Beyond weight, the low-dose combination improved liver enzymes, cholesterol, triglycerides, liver inflammation score (NAS), steatosis, and fibrosis gene expression markers more than either low-dose monotherapy and more than high-dose semaglutide alone. This supports combining FGF21 analogs with GLP-1 drugs for MASH treatment.
Norlin, Jenny; Dermit, Maria; Sidiropoulos, Nikos; Galsgaard, Elisabeth D; Hansen, Henrik H; Feigh, Michael; Veidal, Sanne S; Latta, Markus; Henriksson, Emma; Andersen, Birgitte · Animal
RPEP-12822 · 2025In a secondary analysis of the MAESTRO-NASH phase 3 trial, resmetirom (80 or 100 mg) maintained its efficacy on histological and biomarker endpoints regardless of background GLP-1 RA or SGLT2i therapy. Rates of MASH resolution and fibrosis improvement were similar between patients on and off these diabetes medications. Notably, resmetirom 100 mg patients achieving ≥5% weight loss showed superior outcomes: MASH resolution 56.6% vs. 33.8%, fibrosis improvement 40.6% vs. 31.5%, MRI-PDFF reduction -69% vs. -46%, and liver stiffness reduction -4.6 kPa vs. -2.3 kPa at 52 weeks.
Noureddin, Mazen; Rinella, Mary; Taub, Rebecca; Labriola, Dominic; Camacho, Raul C; Alkhouri, Naim; Loomba, Rohit; Bansal, Meena B ·
RPEP-12831 · 2025GLP-1 receptor agonist use in Poland increased from 212 patients in 2018 to 12,836 in 2024. Obesity was the primary diagnosis in 78% of all patients, with the highest rates in liraglutide and tirzepatide users. The dulaglutide group had the highest rate of type 2 diabetes (67%), while tirzepatide users had the lowest (15%).
Oral semaglutide's share grew steadily from 2022, reaching 50% of all semaglutide applications by 2024. Oral semaglutide users tended to be younger females with less aggravating medical history compared to those on injectable forms.
Nowak, Klaudia; Dziewierz, Artur; Sojda, Aleksandra; Zabojszcz, Michał; Szarpak, Łukasz; Dardzinska, Natalia; Jaskulska, Paulina; Siudak, Zbigniew ·
RPEP-12833 · 2025Enteroendocrine cells — hormone-producing cells in the gut lining — are required to maintain a healthy intestinal barrier. When human intestinal organoids were genetically engineered to lack these cells, barrier function deteriorated in both stem cell-like and mature tissue. Adding the peptide hormones PYY (peptide tyrosine-tyrosine) and octreotide (a somatostatin analog) rescued barrier function both at baseline and in the presence of the inflammatory cytokine TNF. Surprisingly, the barrier improvement occurred without significant changes in tight junction protein levels, suggesting a novel mechanism.
Nwako, Jennifer G; Patel, Sparsh D; Roach, Taevon J; Gupte, Saanvi R; Williams, Samara G; Riedman, Anne Marie; McCauley, Heather A · In Vitro
RPEP-12834 · 2025The review identifies several emerging biomarkers for Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome that outperform traditional inflammatory markers like CRP and IL-6. Soluble urokinase plasminogen activator receptor (suPAR) is highlighted as a stable predictor of systemic inflammation linked to CKD, atherosclerosis, and coronary artery disease. Galectin-3 regulates fibrosis and inflammation across multiple organs. Growth Differentiation Factor-15 (GDF-15) indicates mitochondrial dysfunction and cardiovascular aging. MicroRNAs miR-126 and miR-423-5p show promise for tracking vascular integrity and heart failure progression.
These biomarkers support targeted use of SGLT2 inhibitors for cardiorenal protection and GLP-1 receptor agonists or dual GIP/GLP-1 agonists for metabolic and liver-related complications.
Nzobokela, John; Muchaili, Lweendo; Mwambungu, Alick; Masenga, Sepiso K; Kirabo, Annet ·
RPEP-12838 · 2025Researchers reestablished a specialized lab assay (GTPγS binding/immunoprecipitation) to measure how the nociceptin/orphanin FQ peptide activates a specific signaling protein called Gαi-3 in brain tissue. Using rat and postmortem human brain membranes, they showed that nociceptin increased Gαi-3 activation in a dose-dependent manner.
Importantly, the nociceptin response was not blocked by naloxone (a classical opioid antagonist), confirming that the NOP receptor operates through a distinct mechanism from traditional opioid receptors. However, the selective NOP antagonist J-113397 potently inhibited the response, validating receptor specificity.
Odagaki, Yuji; Kinoshita, Masakazu; Honda, Makoto; Meana, J Javier; Callado, Luis F; García-Sevilla, Jesús A; Palkovits, Miklós; Borroto-Escuela, Dasiel Oscar; Fuxe, Kjell · In Vitro
RPEP-12847 · 2025The review found that:
- GHK-Cu is a hydrophilic (water-loving) tripeptide with limited ability to cross the lipophilic (fat-loving) stratum corneum skin barrier
- Liposomes are theoretically capable of improving GHK-Cu skin penetration by encapsulating it in a lipid-compatible carrier
- Methods exist for studying skin permeation of cosmetically active compounds, including Franz diffusion cells and various analytical detection techniques
- However, the transport of liposome-encapsulated GHK-Cu through skin has received very little scientific attention
- This represents a significant research gap between the widespread commercial use of GHK-Cu in skincare products and the actual evidence for its skin penetration effectiveness
Ogórek, Karolina; Nowak, Kinga; Wadych, Emilia; Ruzik, Lena; Timerbaev, Andrei R; Matczuk, Magdalena ·
RPEP-12848 · 2025NC-CV, a peptide designed from Nephila clavata venom gland transcriptome using in silico analysis and machine learning functional prediction, demonstrated dual activities in LPS-stimulated human bronchial epithelial (BEAS-2B) cells: it reduced pro-inflammatory cytokine expression and decreased intracellular reactive oxygen species (ROS) generation while improving cell viability.
Mechanistically, NC-CV blocks TLR4 signaling activation (confirmed by molecular docking simulations), suppressing downstream NF-κB and MAPK inflammatory pathways. Its antioxidant activity was primarily through direct ROS scavenging rather than inducing endogenous antioxidant enzymes. This dual mechanism disrupts the self-reinforcing cycle of inflammation and oxidative stress in airway epithelium.
Oh, Jin Wook; Shin, Min Kyoung; Park, Hye-Ran; Jeong, Sukin; Lee, Minho; Ko, Ji Hyuk; Lee, Jae Young; Jee, Seung-Cheol; Sung, Jung-Suk ·
RPEP-12850 · 2025Switching from DPP-4 inhibitors to oral semaglutide for 24 weeks significantly reduced oxidative stress (measured by the diacron-reactive oxygen metabolites test), improved glucose variability as measured by continuous glucose monitoring, and lowered HbA1c levels compared to continuing DPP-4 inhibitor therapy.
Importantly, while the metabolic and biochemical markers improved significantly, patient-reported treatment satisfaction scores did not differ between groups, indicating the benefits were measurable but didn't translate to a perceived difference in quality of life over this time period.
Ohara, Makoto; Yokoyama, Hiroki; Seino, Hiroaki; Fujikawa, Tomoki; Kohata, Yo; Takahashi, Noriyuki; Irie, Shunichiro; Terasaki, Michishige; Mori, Yusaku; Fukui, Tomoyasu; Yamagishi, Sho-Ichi ·
RPEP-12853 · 2025In 231 patients with heart failure and LVEF >40% (spanning HFmrEF and HFpEF categories), BNP levels were measured at hospital discharge:
- BNP levels were NOT significantly different across the three LVEF groups: HFmrEF median 195 pg/mL, HFpEF (LVEF 50-59%) median 242 pg/mL, and HFpEF (LVEF ≥60%) median 220 pg/mL (P=0.422)
- Despite similar BNP levels across groups, a BNP cutoff of ≥377 pg/mL significantly differentiated event-free survival (P<0.001)
- In multivariate Cox regression, BNP was independently associated with event-free survival after adjusting for LVEF, E/e' (a measure of heart stiffness), and concurrent atrial fibrillation
This means BNP provides prognostic information beyond what other standard heart failure measurements offer.
Ohte, Nobuyuki; Kikuchi, Shohei; Iwahashi, Noriaki; Kinugasa, Yoshiharu; Dohi, Kaoru; Takase, Hiroyuki; Inoue, Katsuji; Okumura, Takahiro; Hachiya, Kenta; Sugiura, Emiyo; Kusunose, Kenya; Kitada, Shuichi; Seo, Yoshihiro ·
RPEP-12865 · 2025Liraglutide at pharmacological concentrations increased the metabolic viability of mouse Leydig cells and reduced reactive oxygen species (ROS) production at all concentrations tested. Mitochondrial performance was significantly enhanced: increased basal respiration, maximal respiration, proton leak, and ATP-linked oxygen consumption rate. Mitochondrial membrane potential and mtDNA copy number were also assessed. Androstenedione (testosterone precursor) production was unchanged, likely due to inherent limitations of the BLTK1 cell line in supporting full steroidogenesis.
Oliveira-Lopes, Bruno; Braga, Patrícia C; Oliveira, Pedro F; Alves, Marco G; Bernardino, Raquel L ·
RPEP-12869 · 2025The review identifies multiple mechanisms by which GLP-1 receptor agonists and DPP-4 inhibitors improve diabetic foot ulcer outcomes:
- Reduce AGE formation and AGE-RAGE-NF-κB inflammatory signaling caused by chronic hyperglycemia
- Promote macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype
- Enhance angiogenesis, inflammation resolution, and tissue regeneration through AMPK, mTOR, and VEGF signaling
- Glycemic stability (via CGM and antihyperglycemic adherence) improves immune cell function and reduces bacterial virulence, enhancing antibiotic effectiveness
- An integrated approach addressing both metabolic and microbial factors is advocated to restore wound homeostasis and reduce amputation risk
Omotosho, Idris Ajibola; Shamsuddin, Noorasyikin; Zaman Huri, Hasniza; Chong, Wei Lim; Rehman, Inayat Ur ·
RPEP-12875 · 2025Active tDCS significantly reduced migraine days compared to sham during the 28-day follow-up (p = 0.008, large effect size ηp² = 0.241). The active group showed a within-group reduction from baseline (Cohen's d = 0.660, p = 0.023), while the sham group did not. However, total headache days did not differ significantly between groups (p = 0.560). Neurophysiologically, active tDCS decreased delta power at frontal brain regions compared to sham, suggesting modulation of central mechanisms.
Ornello, Raffaele; D'Atri, Aurora; De Icco, Roberto; De Santis, Federico; Rosignoli, Chiara; Onofri, Agnese; Vaghi, Gloria; Cammarota, Francescantonio; Brancaccio, Carla; Corrado, Michele; Bighiani, Federico; Grillo, Valentina; Sances, Grazia; Corigliano, Domenico; Salfi, Federico; Tassorelli, Cristina; Ferrara, Michele; Sacco, Simona ·