RPEP-11630 · 2025Key findings across multiple models:
- TET3 expression in circulating monocytes was identified as an independent predictor of heart attack occurrence and patient prognosis in a clinical cohort
- A monocyte-targeting nanoparticle system was engineered using: periodic mesoporous silica loaded with siTET3, PEI/PEG coating, and a CD14 receptor-recognizing peptide (Cys-Gly-Trp-Arg-Arg-Arg-NH₂)
- In vitro: successfully reprogrammed inflammatory monocytes with attenuated pro-inflammatory phenotypes
- In mouse AMI model: markedly reduced infarct size and myocardial fibrosis
- In pig AMI model: substantial suppression of cardiac inflammation and improved post-infarction outcomes after systemic administration
Jin, Hao; Ding, Jiandong; Zhang, Xiaoguo; Cheng, Shouquan; Zhang, Yahao; Wu, Yong; Liu, Cihui; Yang, Sirui; Zhang, Anjian; Ma, Genshan; Lu, Wenbin ·
RPEP-11632 · 2025Combining polyene phosphatidylcholine (PPC) with the GLP-1 peptide agonist liraglutide achieved a 95% clinical effectiveness rate in NAFLD patients versus 83.33% for PPC alone. The combination therapy produced significantly greater reductions in liver enzymes (ALT, AST, GGT), vaspin, and FGF21, along with greater increases in the beneficial adipokine omentin-1.
Jin, Yao; Liu, Tong; Tong, Zhiqiang; Dong, Mei ·
RPEP-11641 · 2025The dipeptidyl peptidase-1 (DPP-1) inhibitor brensocatib — which blocks the enzyme that activates destructive neutrophil proteins — had broad immunomodulatory effects beyond its known impact on serine proteases in bronchiectasis patients. Treatment increased the antimicrobial peptides SLPI and α-defensin-3 in sputum, reduced the inflammatory mucin MUC5AC, and significantly altered 15 cytokines and chemokines including CXCL10, CCL8, CCL7, CCL3, and IL-6. These changes were consistent across both doses (10 mg and 25 mg) and validated in an independent European bronchiectasis cohort. The findings reveal that brensocatib rebalances the inflammatory environment in the airways much more broadly than just reducing protease activity.
Johnson, Emma D; Long, Merete B; Perea, Lidia; Shih, Vivian H; Fernandez, Carlos; Teper, Ariel; Cipolla, David; McIntosh, Eve; Galloway, Rachel; Eke, Zsofia; Shuttleworth, Morven; Hull, Rebecca; Spinou, Arietta; De Soyza, Anthony; Ringshausen, Felix C; Goeminne, Pieter; Lorent, Natalie; Haworth, Charles; Loebinger, Michael R; Blasi, Francesco; Shteinberg, Michal; Aliberti, Stefano; Polverino, Eva; Sibila, Oriol; Shoemark, Amelia; Mange, Kevin; Huang, Jeffrey T J; Stobo, Jamie; Chalmers, James D · Phase 2 Clinical Trial (Biomarker Analysis)
RPEP-11642 · 2025Of 57,975 participants, 54.2% were classified as engaged and 45.8% as non-engaged with the digital platform. At month 3: engaged lost 9% vs non-engaged 5.9% (P<0.001, Cohen d=0.89 — large effect). At month 5: engaged lost 11.53% vs non-engaged 8% (P<0.001, Cohen d=0.56 — moderate effect). Tirzepatide users achieved greater weight loss than semaglutide users at month 5 (13.9% vs 9.5%, P<0.001). Engaged participants were significantly more likely to achieve ≥5%, ≥10%, and ≥15% weight loss thresholds at all time points.
Johnson, Hans; Huang, David; Liu, Vivian; Ammouri, Mahmoud Al; Jacobs, Christopher; El-Osta, Austen ·
RPEP-11647 · 2025A 55-year-old woman with obesity, type 2 diabetes, and a prior history of small bowel obstruction developed severe abdominal pain and was diagnosed with small bowel obstruction after initiating semaglutide therapy. The obstruction was attributed to the drug's mechanism of slowing gastric emptying and altering the migrating motor complex, compounded by her preexisting GI vulnerability.
The patient was treated conservatively with nasogastric decompression and bowel rest, and her condition resolved. However, the case prompted reassessment of continued GLP-1 RA therapy, underscoring that the benefits of glycemic control must be weighed against GI risks in susceptible individuals.
Jones, Matthew; Cappola, James J ·
RPEP-11649 · 2025GLP-1 receptor agonist use was associated with a significantly lower risk of developing nonexudative age-related macular degeneration (AMD) compared to metformin, insulin, and SGLT-2 inhibitors. After 3 years of use, GLP-1 users had 75% lower AMD risk versus metformin (RR 0.25), 72% lower risk versus insulin (RR 0.28), and 58% lower risk versus SGLT-2 inhibitors (RR 0.42).
In the more rigorous propensity score-matched analysis controlling for additional confounders (BMI, hypertension, CKD, diabetes duration), the reduced risk remained significant compared to insulin (HR 0.45; 95% CI 0.27–0.76). This suggests GLP-1 drugs may have a protective effect on the retina independent of blood sugar control, since all comparator groups were also on glucose-lowering medications.
Joo, Julia H; Zhao, Alison H; Chalasani, Meghana; Allan, Kevin C; Rachitskaya, Aleksandra V · Retrospective Cohort
RPEP-11656 · 2025Using transportability analysis — a statistical method that re-weights clinical trial data to match a real-world population — researchers estimated what would happen if the LEADER trial had enrolled VA veterans instead of its original participants.
For major adverse cardiovascular events (MACE): the transported hazard ratio was 0.74 (95% CI 0.61-0.90) in the VA-weighted analysis versus 0.87 (0.78-0.97) in the original LEADER trial, suggesting a 26% risk reduction in veterans compared to 13% in the trial.
For all-cause mortality: HR was 0.71 (0.57-0.89) in the VA-weighted analysis versus 0.85 (0.74-0.97) in LEADER — a 29% reduction versus 15%.
The 3-year absolute risk difference for MACE was 2.0% in the VA-weighted analysis versus 1.6% in LEADER. Results were robust across all sensitivity analyses.
Josey, Kevin; Liu, Wenhui; Warsavage, Theodore; Medici, Morten; Kvist, Kajsa; Derington, Catherine G; Reusch, Jane E B; Ghosh, Debashis; Raghavan, Sridharan ·
RPEP-11659 · 2025CGRP plays an important role in OA synovial inflammation, contributing to the inflammatory cascade that damages joint tissues. However, the review also identifies CGRP's physiological roles in cartilage maintenance and potential contributions to cartilage regeneration.
The dual nature of CGRP in OA — driving inflammation while potentially supporting tissue repair — creates both challenges and opportunities for therapeutic development. The authors highlight innovative strategies for targeting CGRP to enhance cartilage regeneration rather than simply blocking the peptide entirely, as is done in migraine therapy.
Ju, Yucan; Shen, Leyao; Huang, Qiang; Huang, Zeyu ·
RPEP-11662 · 2025Decreases in leptin and increases in obestatin independently predicted HbA1c reduction with dulaglutide, while changes in BMI or abdominal fat were not associated with glycemic improvement. Responders showed greater beta-cell function improvement and more pronounced food craving reductions.
Jung, Inha; Choi, Hangseok; Choi, In Young; Cho, Hyun Joo; Park, So Young; Lee, Da Young; Seo, Ji A; Kim, Nan Hee; Yu, Ji Hee · Prospective Observational
RPEP-11665 · 2025A male in his 40s with C6 AIS B spinal cord injury (15 years prior, BMI 32) lost 31 pounds after 3 months of tirzepatide treatment. His lipid profile improved. Prior interventions (multiple dietitians, increased physical activity) had failed to achieve weight loss. The only adverse effect was heartburn. This represents the first reported case of tirzepatide use in a spinal cord injury patient.
Juszczak, Michael; Shem, Kazuko ·
RPEP-11666 · 2025BPC 157 has demonstrated pleiotropic beneficial effects across numerous preclinical models including tissue injury, inflammatory bowel disease, and CNS disorders. Its safety profile appears favorable with few reported side effects. However, it has not been approved by the FDA or other regulatory authorities due to the absence of sufficient human clinical studies. WADA temporarily banned it in 2022, though it is no longer on the banned list. The review also documents significant commercial and patent interest in the compound.
Józwiak, Michalina; Bauer, Marta; Kamysz, Wojciech; Kleczkowska, Patrycja ·
RPEP-11667 · 2025Semaglutide and lipidized prolactin-releasing peptide (LiPR) — two anti-obesity compounds — did not change the proportion of POMC-expressing neurons when applied to human stem cell-derived hypothalamic neurons or mouse brain tissue. LiPR also did not alter POMC neuron shape, gene expression patterns, or the generation of new POMC neurons in mice. This suggests anti-obesity medications do not work by rewiring the brain's appetite-suppressing neuron population.
Jörgensen, Sara K M; Surridge-Smith, May; Jones, Kimberley; Maletínská, Lenka; Allen, Nicholas D; Petrik, David · In Vitro And Animal
RPEP-11669 · 2025Over 40 peptide drugs have been approved in the last decade, targeting structures ranging from GPCRs to pathogens and treating metabolic disorders, genetic diseases, and acute illnesses. Key advances include:
- Strategies to improve peptide stability: backbone modification, sequence optimization, cyclization, and addition of stabilizing moieties
- Progress in oral peptide delivery, though requiring specialized design or GI tract permeabilization
- Nasal administration emerging as a dual-purpose route: systemic uptake and direct nose-to-brain delivery
- Nose-to-brain delivery already in clinical use for some compounds, though underlying mechanisms remain poorly understood
- Peptides uniquely bridge the gap between small molecules and biologics in terms of structural diversity
Jülke, Eva-Maria; Beck-Sickinger, Annette G ·
RPEP-11673 · 2025Oral administration of engineered L. reuteri secreting iberiotoxin (LrIbTX) achieved comparable efficacy to injected IbTX in treating collagen-induced arthritis in rats. Both treatments significantly improved clinical joint swelling and histologic inflammation versus controls.
IbTX was detected in the sera of healthy rats after oral gavage with LrIbTX, confirming systemic absorption of the intestinally-produced peptide. The oral and injected routes were also equivalent in inhibiting a delayed-type hypersensitivity reaction. No anti-IbTX antibodies were detected with either delivery method, suggesting good tolerability.
Kady, Mohamed R; Elston, R Nicholas; Snyder, Lauren J; Fleischman, Jorie D; Brandt, Madilyn J; Zhu, Duolong; Britton, Robert A; Beeton, Christine ·
RPEP-11675 · 2025Cross-linking mass spectrometry captured 40 contact points between a photo-reactive NPY analog and the intrinsically disordered N-terminus (NT) of the Y2 receptor. Molecular dynamics simulations revealed that these contacts are rapid and transient, with the structurally flexible NT constantly interconverting between conformations.
Mutagenesis of electrostatic hotspots in the NT showed that these residues control the conformational ensemble of the disordered region. Functionally, the transient NT-NPY contacts prolong ligand residence time at the receptor, which is specifically required for efficient recruitment of arrestin-3 but not for Gi protein coupling. This establishes a mechanism by which the disordered N-terminus selectively biases receptor signaling toward arrestin pathways.
Kaiser, Anette; Rojas Echeverri, Juan C; Baischew, Asat; Pankonin, Maik; Leitner, Karl D; Iacobucci, Claudio; Sala, Davide; Ihling, Christian; Müller, Ronny; Ferenc, Rok; Beck-Sickinger, Annette G; Schmidt, Peter; Meiler, Jens; Hildebrand, Peter W; Sinz, Andrea ·
RPEP-11684 · 2025A 44-year-old woman developed drug-induced liver injury (DILI) after semaglutide initiation for weight management. The causal relationship was confirmed by a positive dechallenge-rechallenge pattern: liver enzymes normalized after discontinuation and elevated again when semaglutide was restarted.
The authors conducted a literature review of all reported semaglutide-related DILI cases, finding that hepatotoxicity from semaglutide, while exceedingly rare, is a documented adverse effect that warrants clinical awareness.
Kalsi, Harsimran; Arora, Samneet Singh; Essilfie-Quaye, Kobina; Bassi, Raghav; Akhavan, Neeka; Perbtani, Yaseen; Brar, Tony S ·
RPEP-11686 · 2025Among 97,059 patients across 21 studies (30,981 received preoperative GLP-1RA), postoperative complications showed no increased risk in GLP-1 users (pooled OR: 0.78, 95% CI: 0.59-1.05). Bayesian meta-analysis confirmed this (posterior mean OR: 0.78, 95% credible interval: 0.57-1.12). Meta-regression found no significant effect modifiers. Preoperative weight loss of up to 16.7 kg or 6.0 kg/m² was reported over six months. Overall GRADE certainty of evidence was very low due to observational designs and high heterogeneity (I²=73%).
Kamarajah, Sivesh K; Gudiozzi, Nadia; Findlay, John M; Lee, Matthew J; Pinkney, Thomas; Markar, Sheraz R ·
RPEP-11692 · 2025Serum 25(OH)D, 1,25(OH)₂D, vitamin D binding protein, β-defensin-1, and cathelicidin-1 concentrations were all significantly lower in hospitalized foals compared to healthy foals at multiple time points over 72 hours (p<0.05). Parathyroid hormone (PTH) was significantly higher in sick foals.
Septic foals showed decreased expression of vitamin D receptor (VDR) and CYP27B1 (the enzyme that activates vitamin D) genes, while pro-inflammatory genes TLR-4, TNF-α, and IL-1β were upregulated. Decreased serum 25(OH)D, β-defensin-1, cathelicidin-1, and elevated PTH were each independently associated with higher odds of death in hospitalized foals (p<0.05).
Kamr, Ahmed M; Bartish, Celine; Summers, Jamie; Horton, Julia; Hostnik, Laura D; Orr, Kindra; Browne, Nimet; Dembek, Katarzyna A; Saliba, Caroline; Gomez, Diego E; Toribio, Ramiro E ·
RPEP-11694 · 2025Over 26-72 weeks across 13 RCTs with 13,761 participants, tirzepatide showed identical cancer risk to pooled controls (RR 0.78; 95% CI: 0.53-1.16; P=0.22). Risk was comparable in patients with and without diabetes. Subgroup analyses showed no difference versus placebo, insulin, or GLP-1 receptor agonists. Only the 10 mg dose showed a lower risk of any cancer versus placebo. Despite elevated serum calcitonin with 10 mg and 15 mg doses, no papillary thyroid carcinoma cases were reported in any trial. No specific cancer type showed increased risk with tirzepatide.
Kamrul-Hasan, A B M; Alam, Muhammad Shah; Dutta, Deep; Sasikanth, Thanikai; Aalpona, Fatema Tuz Zahura; Nagendra, Lakshmi ·
RPEP-11695 · 2025Tirzepatide 10 mg reduced UACR by 26.95% more than placebo (p<0.05) and 15 mg reduced it by a similar significant margin (p=0.0008) over 26-72 weeks. All tirzepatide doses outperformed insulin for UACR reduction. The benefit was greater in type 2 diabetes patients (MD -33.25%) than in obese patients without diabetes (MD -7.93%, p=0.001 for difference).
eGFR was comparable across all tirzepatide doses versus insulin (no statistically significant differences). Tirzepatide showed no increased risk of adverse renal events, UTI, nephrolithiasis, acute kidney injury, or renal cancer compared to placebo, insulin, or GLP-1 receptor agonists.
Kamrul-Hasan, Abm; Patra, Shinjan; Dutta, Deep; Nagendra, Lakshmi; Muntahi-Reza, Afm; Borozan, Sanja; Pappachan, Joseph M ·
RPEP-11696 · 2025Across five RCTs studying canagliflozin, empagliflozin, dapagliflozin, and licogliflozin in 269 overweight/obese PCOS patients, SGLT2 inhibitors reduced insulin resistance (lower HOMA-IR, insulin, and fasting glucose), decreased body weight, BMI, waist circumference, and total body fat, and lowered triglycerides. DHEAS levels decreased in two trials, though total testosterone and free androgen index generally did not change.
Notably, the combination of SGLT2i with a GLP-1 receptor agonist produced the most prominent improvements in body composition and metabolic parameters, while SGLT2i combined with metformin showed better effects on hormonal parameters. Menstrual irregularity and hirsutism scores improved. LDL cholesterol slightly increased in most trials. Adverse effects were mostly mild genital infections.
Kamrul-Hasan, Abm; Mondal, Sunetra; Zahura Aalpona, Fatema Tuz; Nagendra, Lakshmi; Dutta, Deep ·
RPEP-11699 · 2025Across 22 RCTs and 32,013 patients:
- MASH Resolution: significantly improved (RR 1.98, 95% CI: 1.57-2.50) — nearly doubling the resolution rate
- Fibrosis Regression: NOT significantly improved (RR 1.18, 95% CI: 0.74-1.88)
- Liver Steatosis: reduced by 11.3% (95% CI: -18.70 to -3.91)
- ELF score (fibrosis marker): reduced by 0.49 (95% CI: -0.70 to -0.29)
- ALT: reduced by 5.55 U/L; AST: reduced by 3.85 U/L
- All-cause mortality: reduced 18% (RR 0.82, 95% CI: 0.74-0.91)
- Cardiovascular risk: reduced 17% (RR 0.83, 95% CI: 0.75-0.92)
- Best results at doses ≥2.0 mg weekly and durations ≥12 months
Kan, Ranran; Wang, Siyi; Meng, Xiaoyu; Guo, Yaming; Li, Danpei; Yu, Xuefeng ·
RPEP-11705 · 2025Using NMR spectroscopy, researchers identified that hydrophobic interactions in p53's transactivation domain are key to its binding with FOXO4's forkhead domain. Based on this structural insight, they designed CPP-CAND — an optimized peptide with reduced negative charges and a cationic cell-penetrating peptide for cellular delivery.
CPP-CAND demonstrated:
- High selectivity for senescent cells over non-senescent cells
- Effective disruption of nuclear FOXO4-p53 foci (the protein complexes keeping senescent cells alive)
- Induction of caspase-dependent apoptosis (programmed cell death)
- Cytotoxicity against senescent cancer cells induced by both doxorubicin and cisplatin (two different chemotherapy agents)
- Practical advantages: composed of natural L-amino acids, shorter sequence length than previous FOXO4-DRI peptide approaches
Kang, Donghoon; Lim, Yeji; Ahn, Dabin; Lee, Jaeseok; Park, Chin-Ju ·
RPEP-11707 · 2025Two ERAP1-responsive peptide linkers (EPLs) were designed to vary antigen processing efficiency by 10-fold. The more efficient EPL produced multiple downstream improvements:
- Increased antigen colocalization with ERAP1 by ~58% compared to SNAs without the linker
- Augmented antigen surface presentation by 30%
- Boosted ex vivo CD8+ T cell proliferation fivefold
- Increased in vivo proinflammatory CD8+ T cells by 5% and effector memory CD8+ T cells by 18%
- Achieved 2.5-fold more effective inhibition of E.G7-OVA lymphoma tumors in vivo
These results demonstrate that rationally designed peptide linkers can spatially bias antigen processing to a specific intracellular compartment (the ER) and dramatically enhance immune stimulation from the same antigen payload.
Kang, Janice; Teplensky, Michelle H; Dittmar, Jasper W; Evangelopoulos, Michael; Hwang, Jeongmin; Mirkin, Chad A ·
RPEP-11714 · 2025At 52 weeks, tirzepatide (10 or 15 mg) produced significantly greater improvements compared to placebo across multiple patient-reported outcome measures: PROMIS Sleep-Related Impairment, PROMIS Sleep Disturbance, Functional Outcomes of Sleep Questionnaire activity levels, EQ-5D-5L quality of life, and most domains of the SF-36 health survey.
Tirzepatide was also associated with greater improvements on the Patient Global Impression of Status and Change scales. In Study 1 (participants not using PAP therapy), Epworth Sleepiness Scale scores (daytime sleepiness) also improved significantly. These subjective benefits complement the previously reported objective improvements in AHI (breathing interruption frequency), hypoxic burden, and cardiovascular risk factors.
Kanu, Chisom; Shinde, Shraddha; Chakladar, Sujatro; Dennehy, Ellen B; Weaver, Terri E; Poon, Jiat Ling; Malhotra, Atul ·
RPEP-11715 · 2025NT-proBNP remains the gold standard biomarker for diagnosing and assessing prognosis in heart failure, but its performance differs significantly between heart failure subtypes. In HFrEF (reduced ejection fraction), elevated NT-proBNP levels strongly correlate with the severity of ventricular dysfunction and reliably guide treatment decisions. However, in HFpEF (preserved ejection fraction), NT-proBNP's diagnostic specificity is reduced because levels are confounded by age, kidney function, and obesity — meaning doctors often need additional imaging or biomarkers to confirm the diagnosis.
The review highlights emerging proteomic biomarkers like soluble ST2 and GDF-15 that complement NT-proBNP by reflecting different molecular pathways of heart remodeling and inflammation. The authors argue that multimarker strategies combining NT-proBNP with these newer biomarkers will be necessary for precision-based heart failure management.
Kanyal, Shweta; Das, Abhirami; Bashir, Anas M Din; Syed, Ahmed H; Aujla, Savvy; Chaudhary, Jainam; Patel, Dharmik; Goel, Ashish · Review
RPEP-11717 · 2025Among 411 adults on GLP-1 drugs, about 1 in 5 reported heightened taste perception — 21.3% noticed sweet foods tasted sweeter, and 22.6% noticed salty foods tasted saltier. These taste changes were significantly linked to better appetite outcomes:
- Increased sweet taste perception → 2× higher odds of feeling full (AOR 2.02), 67% higher odds of reduced appetite, 85% higher odds of reduced cravings
- Increased salty taste perception → 2.17× higher odds of feeling full
All three GLP-1 drugs showed impressive BMI reductions: Wegovy 17.6%, Ozempic 17.4%, Mounjaro 15.5%. Over 58% reported reduced appetite and 63.5% reported increased satiety.
Kapan, Ali; Moser, Othmar; Felsinger, Richard; Waldhoer, Thomas; Haider, Sandra · Observational
RPEP-11719 · 2025ITC and molecular dynamics simulations revealed that binding of the lipopeptides C12-KR12 and C14-KR12 to decavanadate ([V10O28]6-) is non-specific and driven primarily by enthalpic contributions from electrostatic interactions between the peptides' positively charged residues and the anionic vanadate.
Circular dichroism spectroscopy showed that both lipopeptides adopt α-helical conformations at pH 5, with C14-KR12 (myristic acid conjugate) showing greater thermal stability than C12-KR12 (lauric acid conjugate). Critically, interaction with decavanadate disrupted the α-helical structure and reduced thermal stability of both peptides.
Kapica, Martyna; Kamysz, Elżbieta; Grabowska, Ola; Tesmar, Aleksandra; Pająk, Marek; Chmur, Katarzyna; Brzeski, Jakub; Samsonov, Sergey A; Wyrzykowski, Dariusz ·
RPEP-11722 · 2025In vitro and preclinical in vivo experiments revealed weight-loss-independent anti-inflammatory and chondroprotective (cartilage-protecting) properties of GLP-1 RAs in arthritis models. Clinical data for knee osteoarthritis suggests GLP-1 RAs improve pain and function and reduce the risk of surgical intervention, though effects on OA incidence are incompletely understood.
For gout, GLP-1 RAs do not directly prevent attacks but effectively manage the cardiometabolic conditions commonly associated with gout. Evidence for effects on incidence, disease activity, and progression of rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis remains limited and requires further research.
Karacabeyli, Derin; Lacaille, Diane ·
RPEP-11724 · 2025The review summarizes evidence that GLP-1R activation improves coronary microvascular function through multiple mechanisms:
- Improved endothelial function in coronary microvasculature
- Increased nitric oxide bioavailability
- Attenuation of oxidative stress
- Reduced vascular inflammation
- Improved myocardial blood flow and myocardial perfusion reserve
- Enhanced coronary endothelial function, particularly in high-risk populations with T2D
- Benefits extend beyond glycemic control to direct cardiovascular effects
- Inconsistencies across studies due to variability in populations, designs, and imaging methods
Karakasis, Paschalis; Patoulias, Dimitrios; Theofilis, Panagiotis; Pamporis, Konstantinos; Sagris, Marios; Vlachakis, Panayotis K; Koufakis, Theocharis; Antoniadis, Antonios P; Fragakis, Nikolaos ·
RPEP-11725 · 2025Over 26 weeks, semaglutide produced a 22.6% reduction in total daily insulin dose (95% CI: -28.3 to -17.0), driven by a 30.5% reduction in bolus insulin and 15.6% reduction in basal insulin. The basal/TDD ratio increased from 0.56 to 0.62. Insulin dose decreased from 0.72 to 0.60 units/kg/day.
Mediation analysis showed that at week 4, 83% of the TDD reduction (-11.1 U/day) was a direct drug effect and only 17% (-2.3 U/day) was from weight loss. By week 26, it was 52% direct effect (-11.4 U/day) and 48% weight loss (-10.5 U/day). Daily carbohydrate intake decreased from 137g to 107g.
Karakus, Kagan E; Akturk, Halis K; Kruger, Davida; Ahmann, Andrew; Bharvaga, Anuj; Langel, Christine R; Ackeifi, Courtney A; Rosen, Jonathan; Pyle, Laura; Snell-Bergeon, Janet K; Shah, Viral N ·
RPEP-11727 · 2025In rodent models, liraglutide positively influenced bone material properties despite weight loss, but the most favorable effects on bone mineral density and microarchitecture occurred at doses much higher than those approved for human obesity treatment.
In humans with obesity, preliminary findings indicate GLP-1 receptor agonists cause modest bone mineral density reduction and enhance bone remodeling that favors resorption — a pattern similar to the effects seen with calorie restriction producing 7–10% weight loss. Significant weight reduction through calorie restriction or bariatric surgery consistently results in high-turnover bone loss.
Karam, Léa; Mabilleau, Guillaume; Paccou, Julien ·
RPEP-11731 · 2025BNP (B-type natriuretic peptide) and NT-proBNP showed comparable diagnostic accuracy for heart failure in patients presenting with acute dyspnea. Across 26 studies (n=16,002) for BNP and 14 studies (n=6,313) for NT-proBNP, pooled sensitivity and specificity overlapped with no statistically significant difference between the two biomarkers.
As with any threshold-dependent test, raising the BNP cutoff increased specificity but decreased sensitivity. The lowest reported sensitivity was 0.76 at a BNP cutoff of ≥500 pg/mL in a study with 46% heart failure prevalence. The authors note a residual risk of missed heart failure diagnoses with either biomarker.
Karimi, Mohammad Amin; Kazemi Ferezghi, Zahra; Khademi, Reza; Mazhari, Seyed Amirhossein; Chichagi, Fatemeh; Rasouli, Asma; Alikhani, Reyhaneh; Sani, Anis; Akhavan Rezayat, Shima; Shakouri, Nima; Azimi, Seyed Iraj; Jadidian, Faezeh; Nikeghbali, Golnaz; Edrisian, Mahfam; Alizadeh, Alaleh; Deravi, Niloofar; Poudineh, Mohadeseh; Asadi Anar, Mahsa · Meta Analysis
RPEP-11732 · 2025Among 270 patients with uncontrolled hypertension, esaxerenone treatment produced significant nocturnal blood pressure reductions across all groups:
- Monotherapy (n=172): 24h SBP -10.0 mmHg
- With calcium channel blocker (n=49): 24h SBP -6.0 mmHg
- With RAAS inhibitor (n=49): 24h SBP -17.0 mmHg
Nighttime systolic BP decreased significantly (P < 0.001) in all groups by week 28, with the RAAS inhibitor combination showing the greatest effect (-20.6 mmHg nighttime SBP). NT-proBNP (N-terminal pro-B-type natriuretic peptide), a peptide biomarker of cardiovascular prognosis, decreased significantly in all three treatment groups.
Kario, Kazuomi; Ito, Sadayoshi; Itoh, Hiroshi; Rakugi, Hiromi; Okuda, Yasuyuki; Yamakawa, Satoru ·
RPEP-11738 · 2025Pooled analysis of 4 RCTs (n=3,553) demonstrated:
- Mean body weight reduction: -16.54% vs. placebo (95% CI: -17.48 to -15.59; p<0.00001)
- Clear dose-response: each 1 mg increase in tirzepatide added -0.72% more weight loss (meta-regression p=0.0014)
- Achievement of ≥15% weight loss: OR 23.25 (95% CI: 18.06-29.94)
- BMI reduction: -7.09 kg/m²
- Waist circumference reduction: -12.77 cm
- HbA1c improvement: -0.42%
- Quality of life improved (SF-36v2 and IWQOL-Lite-CT scores)
Safety: Nausea (OR 4.20), vomiting (OR 6.93), and diarrhea (OR 3.80) were more common, but serious adverse events were comparable to placebo (OR 0.97).
Kasagga, Alousious; Assefa, Amanuel Kefyalew; Amin, Maysaa N; Hashish, Rahma; Agha Tabari, Khaled; Swami, Shivling S; Nakasagga, Kevin ·
RPEP-11744 · 2025Tirzepatide treatment in 95 people with type 2 diabetes led to significant reductions in HbA1c (from 7.4% to 6.4%) and body weight (from 77.2 kg to 70.6 kg). Notably, despite tirzepatide's appetite-suppressing effects, patients reported significantly improved diet-related quality of life — specifically their perception of dietary therapy's benefits increased from a median score of 58.3 to 67.7 (p<0.01).
Multiple regression analysis showed that both BMI reduction and improved diet-related quality of life were independent predictors of overall treatment satisfaction, with comparable effect sizes.
Kato, Shunsuke; Kokita, Ayaka; Akanuma, Hana; Iwamura, Shogo; Takahashi, Yuya; Kusumi, Ryota; Abe, Sakiko; Sasaki, Kana; Otomo, Hitomi; Ando, Sayaka; Nara, Mitsuhiko; Nara, Aiko; Tadika, Takenobu; Shimizu, Tatsunori; Sato, Takehiro; Morii, Tsukasa; Fujita, Hiroki; Matsuda, Daisuke; Waki, Hironori ·
RPEP-11746 · 2025Semaglutide showed the strongest psychiatric safety signals: depressive symptoms (ROR = 6.24, CI 4.49–8.69 in FAERS), suicidal ideation (ROR = 2.58, CI 2.31–2.88 in FAERS), and panic attacks (ROR = 1.46, CI 1.16–1.82 in FAERS). Liraglutide was linked to depression in the Canadian database (ROR = 1.68, CI 1.12–2.51). Dulaglutide was associated with eating disorders (ROR = 1.47, CI 1.26–1.71) and insomnia (ROR = 2.93, CI 2.35–3.66) in FAERS.
Significant associations were identified when multiple databases showed elevated reporting odds ratios, strengthening the signal reliability.
Katranski, Jonah; Liang, Sihua; Morris, Deirdre; Suppiah, Vijayaprakash; Lim, Chiao Xin ·
RPEP-11750 · 2025Preclinical research demonstrates that peptide-based therapies targeting four major neuronal systems — opioid, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), and glutamate — can reduce alcohol intake, demand, and relapse in animal models of alcohol use disorder. Opioid peptides (β-endorphin, enkephalins) modulate alcohol reward via µ, δ, and κ receptors; CRF peptides reduce stress-driven alcohol seeking; and NPY peptides decrease cravings and anxiety. Early clinical trial results show translational potential, though challenges remain in establishing safety and efficacy in humans.
Katturajan, Ramkumar; Evan Prince, Sabina; Valsala Gopalakrishnan, Abilash ·
RPEP-11753 · 2025Ltc2a exhibited selective cytotoxicity toward cancer cells compared to normal cells at just 2 μM concentration. The peptide induced rapid cell death within 1 hour in breast cancer cells through membrane disruption, confirmed by propidium iodide staining and scanning electron microscopy showing visible membrane damage.
In vivo zebrafish studies demonstrated favorable peptide uptake with 80% survival at concentrations up to 4 μM, indicating low acute toxicity. Truncated variants of Ltc2a retained their alpha-helical structure and showed preferential uptake in MDA-MB-231 triple-negative breast cancer cells over normal HEK293T cells.
Kaur, Prasanjeet; Roy, Srabaita; Minocha, Shilpi; Chugh, Archana ·
RPEP-11761 · 2025Median cumulative tumor dose was 2.2 Gy/GBq (range 0.1–20.8) while median kidney dose was 0.44 Gy/GBq (range 0.25–0.96). The tumor-to-kidney dose ratio declined with each cycle: 6.4, 5.7, 4.7, and 3.9 for cycles 1 through 4, driven by decreasing tumor uptake while kidney dose stayed constant.
Higher-grade (grade 2) and pancreatic NETs showed a larger drop in dose per cycle and had lower overall absorbed doses and shorter effective half-lives compared to low-grade (grade 1) and small intestinal NETs.
Kidney radiation dose significantly predicted kidney function decline at 9 months. In a multivariable model adjusting for baseline kidney function, cycle 1 dose alone predicted 57% of the variance in later kidney function (p=0.020), and cumulative dose predicted 65% (p=0.049).
Kayal, Gunjan; Roseland, Molly E; Wang, Chang; Fitzpatrick, Kellen; Mirando, David; Suresh, Krithika; Wong, Ka Kit; Dewaraja, Yuni K ·
RPEP-11766 · 2025In a surprising finding, GLP-1 and dual GLP-1/GIP drugs (semaglutide and tirzepatide) were associated with substantially reduced — not increased — risks of gallstone-related complications in patients who have both type 2 diabetes and inflammatory bowel disease. After propensity score matching 32,052 patients (16,026 per group), the GLP-1 group had significantly fewer cases of gallstones (cholelithiasis), gallbladder inflammation (cholecystitis), bile duct stones (choledocholithiasis), and bile duct infection (cholangitis).
This contradicts the general concern that GLP-1 drugs increase gallbladder problems, though this specific population (T2DM + IBD) has a uniquely high baseline risk for biliary complications.
Kazi, Muhammad Ali Ibrahim; Singh, Sanmeet; Haq, Nowreen · Retrospective Cohort Study
RPEP-11769 · 2025The review identifies three neuropeptides — CGRP, substance P, and VIP — as potential biological links between psoriasis and psychiatric comorbidities. These neuropeptides are active in skin (where they drive inflammation and psoriatic lesion formation) and in the brain (where they influence mood, stress responses, and anxiety circuits).
Inflammatory cytokines elevated in psoriasis (IFN-γ, IL-1, IL-2, IL-6, IL-12, TNF-α, IL-22, IL-17) also cross the blood-brain barrier and affect neurotransmitter systems involved in depression. The HPA stress axis provides a bidirectional pathway where psychological stress can worsen psoriasis and psoriatic inflammation can exacerbate depression and anxiety.
Keenan, Emily L; Granstein, Richard D ·
RPEP-11774 · 2025The FDA black-box warning for GLP-1 RAs applies to patients with personal/family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome, based on rodent C-cell tumor data. For differentiated thyroid cancer (DTC), the evidence is conflicting: some epidemiological studies suggest increased DTC incidence in GLP-1 RA-treated patients, while others find no association. No clinical consensus exists on whether to screen patients for thyroid cancer before starting GLP-1 drugs or how to evaluate thyroid nodules found during treatment.
Kelly, Clare A; Sipos, Jennifer A ·
RPEP-11776 · 2025Formula diet-based lifestyle interventions produced greater weight reductions than pharmacological therapies including GIP/GLP-1 RAs and SGLT-2 inhibitors at both short-term (mean: -5.6 vs -2.6 kg under 12 months) and long-term intervals (-7.3 vs -3.1 kg at 12+ months).
For HbA1c reduction, pharmacological therapies showed a slight short-term advantage (-0.9% vs -0.6%), but long-term glycemic control was comparable between lifestyle and drug interventions (both approximately -0.7%). These results were based on 54 articles describing 3 formula diet-based programs and 47 randomized placebo-controlled pharmacological studies with a total of 87,871 patients.
Kempf, Kerstin; Röhling, Martin; Martin, Stephan ·
RPEP-11777 · 2025A middle-aged female patient presented with rapidly worsening liver function tests one month after starting semaglutide. The clinical workup was thorough:
- Non-invasive liver screen: negative
- Viral hepatitis studies: negative
- Ultrasound and CT imaging: no structural cause identified
- Liver biopsy: findings consistent with drug-induced liver injury
The patient experienced transient liver failure but improved with supportive treatment and withdrawal of semaglutide. No other cause for the liver injury was identified, supporting semaglutide as the causative agent.
Kempster, Ian; Fernandes, Darren; Saeed, Mohammed S; Sharratt, Caroline; Benfield, Sara ·
RPEP-11779 · 2025The review identifies the molecular connections between type 2 diabetes and Alzheimer's disease:
- Impaired brain insulin signaling leads to neuronal degeneration and reduced synaptic activity
- GLP-1 naturally plays a role in brain glucose control and insulin signaling
- GLP-1 receptor agonists demonstrate neuroprotective properties including: prevention of neuronal death, inhibition of amyloid-beta (Aβ) accumulation, and mitigation of tau hyperphosphorylation
- Semaglutide, despite being the most widely used GLP-1RA, has had limited focused neuroprotection studies compared to older GLP-1 drugs like liraglutide and exenatide
The review calls for more semaglutide-specific research given its unique pharmacological properties (longer half-life, higher potency) compared to earlier GLP-1 drugs.
Kenzheshova, Akniyet; Moldasheva, Aiman; Aljofan, Mohamad ·
RPEP-11784 · 2025LL-37, the only human cathelicidin antimicrobial peptide, has demonstrated activity across three domains of infection — bacterial, fungal, and viral — through distinct mechanisms. Against bacteria, it disrupts cell membranes. Against fungi, it inhibits growth. Against viruses, it interferes with replication. Additionally, LL-37 shows immunomodulatory effects and direct cytotoxicity against cancer cells, positioning it as a potential multi-purpose therapeutic molecule.
Keshri, Anand K; Rawat, Suraj S; Chaudhary, Anubha; Sharma, Swati; Kapoor, Ananya; Mehra, Parul; Kaur, Rimanpreet; Mishra, Amit; Prasad, Amit ·
RPEP-11789 · 2025After 1:3 propensity score matching on 10 variables (age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking, osteoporosis, levels of surgery, and insulin dependence), the semaglutide-exposed group showed a dramatically higher odds of needing additional lumbar fusion surgery within one year: OR 11.79 (95% CI 8.17–17.33).
Kaplan-Meier survival analysis with log-rank testing confirmed a statistically significant divergence in the probability of additional surgery between cohorts (P < 0.001). The association was stronger in patients receiving semaglutide for longer durations, suggesting a dose-duration relationship.
Khalid, Syed I; Massaad, Elie; Thomson, Kyle; Shin, John H ·
RPEP-11794 · 2025A 72-year-old woman with cognitive impairment, type 2 diabetes, atrial fibrillation, obesity, and mood disorders was unable to escalate her semaglutide dose due to severe nausea, vomiting, and diarrhea. After initiating mirtazapine:
- Gastrointestinal tolerance improved significantly
- Semaglutide therapy was continued with successful dose advancement
- Additional benefits included enhanced mood, better sleep, and improved overall well-being
- No adverse effects related to mirtazapine were observed
The case suggests mirtazapine may serve as an adjunct therapy to improve GLP-1 RA tolerability and adherence.
Khan, Ali R; Makhoul, Gennifer Wahbah; Raji, Mukaila A ·
RPEP-11803 · 2025The review identifies several key families of plant antimicrobial peptides:
- Plant defensins — small cysteine-rich peptides with broad-spectrum antimicrobial activity
- Thionins — toxic peptides that disrupt pathogen cell membranes
- Cyclotides — exceptionally stable cyclic peptides with a wide range of biological activities
Transgenic overexpression of AMP genes in plants increases pathogen resistance, while pathogen mutants susceptible to these peptides show decreased virulence — confirming the peptides' direct role in defense. The review emphasizes that plant AMPs exhibit activity against diverse pathogens and could serve as templates for new antimicrobial drugs for human use.
Khan, Shaina Shahab; Luqman, Suaib ·