RPEP-10794 · 2025This systematic review and meta-analysis pooled data from 3 randomized controlled trials involving 1,088 patients with diabetes and/or obesity. Survodutide at 2.4 mg/week produced a mean body weight reduction of 7.79% compared to placebo. HbA1c also decreased significantly.
However, the 2.4 mg dose was associated with nearly 3 times the odds of treatment-emergent adverse events (OR 2.93) compared to placebo, though severe adverse events were not increased. Gastrointestinal side effects were the most common and were dose-dependent. Treatment discontinuation due to side effects was also significantly higher with survodutide and increased with dose. The authors concluded that the optimal dose range appears to be 2.4 to 4.8 mg/week.
Dutta, Deep; Kamrul-Hasan, Abul B M; Joshi, Ameya; Dhall, Anil; Nagendra, Lakshmi; Sharma, Meha · Meta Analysis
RPEP-10800 · 2025Among 95 dulaglutide users and 135 oral semaglutide users, compliance with all package leaflet administration instructions was 96.8% for weekly injectable dulaglutide versus 90.4% for daily oral semaglutide. After adjusting for potential between-group imbalances, the odds ratio for higher compliance with dulaglutide was 3.2 (95% CI: 1.4-21.3), indicating significantly better adherence to administration instructions.
The lower compliance with oral semaglutide is attributed to its complex administration requirements: taking it first thing in the morning on an empty stomach with no more than 120 mL of plain water, then waiting at least 30 minutes before eating, drinking, or taking other medications.
Díaz-Cerezo, Silvia; Artime, Esther; Redondo-Antón, Jennifer; Duque, Natalia; Spaepen, Erik; Mangas Cruz, Miguel Ángel; Arnas-Leon, Claudia; Olveira, Gabriel; Rodríguez, Irene Rodríguez; Julián Alagarda, María Teresa; Valdés, Nuria; Merchante, Agustín Ángel; Masmiquel, Lluís; Rubio-de Santos, Miriam ·
RPEP-10806 · 2025ToxIR, a new RNA-seq computational pipeline, identified 378 putative toxin peptide candidates from scorpion venom glands, including 192 high-confidence candidates and 23 novel divergent toxins not previously described. The pipeline found 180 sodium channel, 111 potassium channel, and 69 chloride channel toxin peptides. ToxIR minimizes assembly errors and annotation bias through its modular design combining deep sequencing, de novo assembly, structural analysis, and curated toxin database searches.
Ebadi, Mehran; Soorki, Maryam Naderi ·
RPEP-10809 · 2025A systematic drug repurposing screen in nphp1/nphp4-depleted zebrafish identified GLP-1 signaling as a novel therapeutic target for nephronophthisis. DPP-4 inhibitors (omarigliptin and linagliptin) and the GLP-1 receptor agonist semaglutide significantly reduced cystogenesis in a dose-dependent manner. Genetic analysis confirmed GLP-1 receptors (gcgra and gcgrb) are important for pronephros integrity. Transcriptomics identified adenosine receptor A2ab (adora2ab) as a key downstream effector regulating ciliary morphology. Nphp1/nphp4 double mutant zebrafish showed compensatory upregulation of GLP-1 receptor genes, and disrupting this compensation enhanced cyst formation.
Eckert, Priska; Nöller, Maike; Müller, Merle; Haas, Rebecca; Ruf, Johannes; Franz, Henriette; Moos, Katharina; Yu, Jia-Ao; Zhao, Dongfang; Xie, Wanqiu; Boerries, Melanie; Walz, Gerd; Yakulov, Toma A ·
RPEP-10810 · 2025The Evaluate Renal Function with Semaglutide Once Weekly trial demonstrated that semaglutide significantly reduced the risk of major kidney outcomes including kidney failure, death from kidney or cardiovascular causes, reduced albuminuria, and major cardiovascular events.
Based on this and supporting evidence, guidelines now position semaglutide as the fourth pillar of diabetic kidney disease therapy, complementing SGLT2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and renin-angiotensin-aldosterone system blockers. The review also notes emerging evidence for kidney-protective effects in people without diabetes, and metabolic benefits not achievable with the other three standard therapies.
Economos, Harry; MacIsaac, Richard J ·
RPEP-10822 · 2025Among 366 patients (122 liraglutide, 244 semaglutide) with similar baseline characteristics (mean age ~51, mean weight ~94.6-94.7 kg):
- **Weight loss**: No significant difference between liraglutide and semaglutide (P = 0.867)
- **HbA1c reduction**: Semaglutide was significantly superior — median reduction of -0.5% vs. -0.2% for liraglutide (P = 0.003)
- **Lipids**: Both drugs significantly lowered LDL cholesterol and triglycerides
- **Multivariable analysis**: Confirmed no significant difference in weight loss between drugs (B -0.577, 95% CI -1.87 to 0.7; P = 0.38)
- Baseline weight, diabetes status, and SGLT2 inhibitor use were identified as significant factors affecting weight outcomes
El Nekidy, Wasim S; Hasan, Haneen; Abidi, Emna; Al Sayegh, Layth; Dajani, Ruba Z; El-Kaissi, Samer; Hegazin, Safa B; Mallat, Jihad ·
RPEP-10824 · 20255-FU administration caused marked increases in hepatic enzyme levels, oxidative stress markers (malondialdehyde), inflammatory markers (TNF-α, IL-6), and histological liver injury in rats.
Semaglutide pretreatment (0.3 mg/kg orally) effectively counteracted these harmful effects through multiple pathways: it suppressed the ROS/NF-κB/NLRP3 inflammasome inflammatory cascade, reduced oxidative stress (lowering MDA while increasing glutathione), decreased apoptosis (reducing caspase-3), and activated the pCREB/Nrf2/HO-1 antioxidant signaling pathway.
Critically, semaglutide enhanced PINK1/Parkin-mediated mitophagy — the process of removing damaged mitochondria. When chloroquine (an autophagy inhibitor) was co-administered with semaglutide, the protective effects were abolished, confirming that mitophagy enhancement is a key mechanism of semaglutide's hepatoprotective action.
El Sayed, Nermein F; Baraka, Sara A; El-Mokadem, Bassant M; El Osaily, Heba H; Bishr, Abeer ·
RPEP-10825 · 2025When Staphylococcus aureus evolves resistance to antimicrobial peptides (AMPs), it pays a hidden cost: it becomes more vulnerable to other immune defenses. Researchers found that S. aureus strains resistant to tenecin 1 (an insect AMP) showed "collateral sensitivity" to phenoloxidase (another immune effector) and to other AMPs in the host's defense arsenal.
This trade-off explains a paradox: AMP-resistant bacteria don't actually become more virulent in living hosts, even though they can survive exposure to individual AMPs in a test tube. In the mealworm beetle model, AMP-resistant S. aureus didn't increase host mortality or bacterial load compared to wild-type bacteria. The immune system's use of multiple, diverse antimicrobial mechanisms creates an evolutionary trap — resistance to one peptide comes at the cost of vulnerability to others.
El Shazely, Baydaa; Rolff, Jens · In Vivo Experimental Study
RPEP-10833 · 2025In female mice with nitroglycerin-induced migraine, sulforaphane (5 mg/kg/day for 9 days) showed significant improvements:
- Behavioral: Reduced photophobia, head grooming, mechanical and thermal allodynia
- Biochemical: Lowered serum nitric oxide, CGRP, and pro-inflammatory cytokines
- Histological: Ameliorated damage in trigeminal ganglia and trigeminal nucleus caudalis
- Molecular: Reduced AMY1 receptor expression in the medulla; inhibited downstream phospho-ERK1/2, P38, and c-Fos signaling
- Enhanced Nrf2/HO-1 antioxidant pathway while suppressing NF-κB/NLRP3/caspase-1 inflammatory cascade
Effects were comparable to the standard migraine medication topiramate (30 mg/kg/day).
Elbendary, Luejine A; Abdel-Latif, Ghada A; Khattab, Mohamed A; El-Sahar, Ayman E; Sayed, Rabab H ·
RPEP-10834 · 2025Pre-hydrolysed pea protein achieved a 64% degree of hydrolysis during pepsin digestion, compared to approximately 40% for non-hydrolysed samples. The resulting peptides showed stronger inhibition of key metabolic enzymes.
After ultrafiltration to concentrate small peptides (<10 kDa), the bioactive effects were dramatically enhanced:
- α-amylase inhibition: up to 44.5%
- α-glucosidase inhibition: up to 54%
- ACE inhibition: up to 95%
Peptidomic analysis identified unique peptide sequences in the pre-hydrolysed fractions, and computational modeling confirmed their bioactive potential.
Elbira, Arig; Hernández-Álvarez, Alan Javier; Boesch, Christine ·
RPEP-10836 · 2025Cathelicidin (LL-37) immunohistochemical expression was significantly elevated in vitiligo patients compared to controls (p < 0.001). Lesional skin showed a mean expression score of 2.85 ± 0.67, while non-lesional skin scored 2.05 ± 0.51 — both significantly higher than control skin.
Cathelicidin levels in both lesional and non-lesional skin correlated significantly with the VIDA (Vitiligo Disease Activity) score (p < 0.001 and p = 0.016, respectively), linking higher LL-37 expression to more active disease.
Notably, the elevated cathelicidin in apparently normal-looking skin of vitiligo patients suggests LL-37 may be involved before visible depigmentation occurs, potentially serving as a predictive biomarker for future lesion development.
Elgarhy, Lamia Hamouda; Ramadan, Basma Ramadan Refaey; Sallam, Fersan Abd Allah; Iskandarani, Dalya Ayman; Hewedy, El-Sayed Shaaban ·
RPEP-10841 · 2025This review highlights that a 6-week randomized controlled trial demonstrated the GLP-1 receptor agonist liraglutide was superior to colesevelam (the standard bile acid sequestrant treatment) for reducing bile acid diarrhea (BAD) symptoms. The authors review the broader literature on GLP-1 RAs for BAD, discuss potential mechanisms of action, and argue that newer, more potent GLP-1 RAs could offer even greater benefits for this underserved patient population.
Ellegaard, Anne-Marie; Kårhus, Martin L; Winther-Jensen, Matilde; Lund, Asger B; Knop, Filip K · Review
RPEP-10843 · 2025In a 6-month trial of 73 people with HIV and abdominal obesity, tesamorelin (2 mg daily subcutaneous) significantly reduced waist circumference compared to standard of care (median difference -2.7 cm, p=0.015). However, while the tesamorelin group showed a trend toward improved cognitive performance (mean change 0.146, p=0.060), the between-group difference in cognition was not statistically significant (p=0.673). IGF-1 levels increased with tesamorelin but did not correlate with cognitive changes or waist circumference reduction.
Ellis, Ronald J; Vaida, Florin; Hu, Keren; Dube, Michael; Henry, Brook; Chow, Felicia; Heaton, Robert K; Lee, Daniel; Sattler, Fred · Randomized Controlled Trial
RPEP-10846 · 2025Peptide and protein drugs now account for approximately 25% of the global pharmaceutical market. The FDA, ICH (International Council for Harmonisation), and EMA (European Medicines Agency) have each established specific guidelines for the analysis, stability testing, and quality control of peptide and protein therapeutics. The review summarizes these frameworks and advocates for tailored bioanalytical workflows for each individual peptide or protein drug, since each has unique stability and characterization requirements.
Elsayed, Yomnah Y; Kühl, Toni; Imhof, Diana ·
RPEP-10852 · 2025Semaglutide and bariatric surgery (vertical sleeve gastrectomy) induce fundamentally different changes in fat tissue composition at the single-cell level. While both cause weight loss, the cellular landscape of fat tissue after each treatment differs from each other and from never-obese lean animals. Some cell populations return to a lean-like state while others persist in an obese-like configuration. This means weight-loss fat tissue retains a 'memory' of obesity that differs depending on how the weight was lost.
Emont, Margo P; Essene, Adam L; Gulko, Anton; Bozadjieva-Kramer, Nadejda; Jacobs, Christopher; Nagesh, Soumya; Seeley, Randy J; Tsai, Linus T; Rosen, Evan D ·
RPEP-10855 · 2025Using knockout mice, the study distinguished the roles of two opioid peptides:
- Mu-opioid receptor (MOR) knockout mice: reduced binge eating on high-fat diet re-exposure, diminished food devaluation after 7-day HFD exposure, and failed to show conditioned food reward
- Beta-endorphin (β-END) knockout mice: reduced binge eating and diminished food reward, but normal food devaluation
- Enkephalin (ENK) knockout mice: no significant changes in binge eating, food reward, or food devaluation
All genotypes showed normal initial food intake for both regular chow and high-fat diet, indicating these peptides specifically affect binge/reward behaviors rather than basic hunger.
Era, Iffat Hasnin; Hamid, Abdul; Lutfy, Kabirullah ·
RPEP-10858 · 2025Among 120 sports science students (63 females, 57 males, ages 18-25), males scored significantly higher on the Muscle Dysmorphic Disorder Inventory than females. Salivary asprosin levels were significantly higher in males compared to females. The study found associations between bigorexia nervosa levels and endocrine markers (asprosin, GLP-1) as well as the cerebral marker BDNF, though no significant correlation was found between BMI and GLP-1 or BDNF levels (p>0.05).
The average MET value was 4.53, indicating moderate-intensity physical activity across participants. The study suggests bigorexia nervosa influences physiological and hormonal responses beyond just behavioral patterns.
Erkılıç, Ali Ozan; Bayraktar, Bülent; Erkiliç, Tuğçe Orkun; Türkmen, Mutlu; Kul, Murat; Yönal, Mehmet ·
RPEP-10865 · 2025Across 11 observational studies, preoperative GLP-1 receptor agonist use enhanced weight loss before metabolic and bariatric surgery, allowing patients to reach surgical eligibility sooner. The drugs were associated with improved diabetes outcomes post-surgery.
However, preoperative GLP-1 RA use was linked to increased postoperative nausea. There were no significant differences in major complication rates or readmissions. Some studies noted higher surgical adhesion rates. Findings on postoperative weight loss specifically were inconsistent across studies.
Esparham, Ali; Sheikhbahaei, Erfan; Anari Moghadam, Hengameh; Khorgami, Zhamak ·
RPEP-10872 · 2025In a meta-analysis of 14 randomized trials (25,167 patients), sacubitril/valsartan reduced heart failure rehospitalization by 15% compared to ACE inhibitors or ARBs regardless of ejection fraction (RR: 0.85; P=0.00001). All-cause mortality was reduced by 12% but only in patients with ejection fraction ≤40% (RR: 0.88; P=0.0006) — no mortality benefit was seen in patients with higher ejection fractions. Notably, cardiovascular mortality was not significantly reduced in any ejection fraction group.
Evbayekha, Endurance; Idowu, Abiodun Benjamin; LaRue, Shane · Meta Analysis
RPEP-10875 · 2025In this Phase 1 trial, 69 healthy volunteers received imapextide at various doses (10-200 mg single dose; 10-30 mg weekly for 4 weeks) or placebo. The drug demonstrated dose-proportional exposure with a median time to peak concentration of 24-48 hours and a mean half-life of approximately 90 hours, supporting once-weekly administration.
The most common side effects were injection site reactions (erythema and swelling). During mixed meal tolerance tests, imapextide increased GLP-1 concentrations at early time points and slightly accelerated gastric emptying. Drug-drug interaction studies showed minimal, non-clinically relevant interaction with rosuvastatin. These findings support further development for post-bariatric hypoglycemia treatment.
Fabbrini, Elisa; Koshkina, Anastasiya; Hackett, Michael; Zhao, Michael; Thalluri, Kishore; Hompesch, Marcus; Macias, Alejandra; Schneider, Kristi; D'Alessio, David A; DiMarchi, Richard D; Azoulay, Salomon ·
RPEP-10877 · 2025SURPASS-CVOT compared tirzepatide to dulaglutide (not placebo) for major adverse cardiovascular events (MACE) in type 2 diabetes. Tirzepatide demonstrated noninferiority with an HR of 0.92 (95.3% CI: 0.83–1.01, P = 0.086), but superiority over dulaglutide was narrowly missed. Against an imputed placebo, tirzepatide showed a potential 28% MACE risk reduction.
Notably, tirzepatide achieved substantially better metabolic outcomes — 0.8% greater HbA1c reduction and 7% more weight loss than dulaglutide — yet this translated to only modest incremental cardiovascular benefit. Exploratory analyses showed promising signals for reduced mortality and better kidney function, but these require cautious interpretation. The disconnect between dramatic metabolic improvements and limited extra heart protection is the central finding of this commentary.
Fadini, Gian Paolo ·
RPEP-10880 · 2025The review identifies several forensic challenges posed by semaglutide and other GLP-1 agonists:
- Semaglutide's large, highly charged molecular structure makes it difficult to detect and quantify using standard forensic laboratory instrumentation
- The drug may have limited stability in whole blood samples, further complicating post-mortem analysis
- Side effects relevant to forensic cases include hypoglycemia (which can impair driving and other performance), drug-drug interactions, and potential contribution to unexpected fatalities
- Off-label use and misuse for weight loss expand the population potentially affected
- No robust analytical methods currently exist for routine forensic toxicology casework involving semaglutide
Fagiola, Michael ·
RPEP-10881 · 2025Both semaglutide and tirzepatide share common side effects including gastrointestinal issues (nausea, vomiting, pancreatitis, diarrhea), bone remodeling changes, kidney disorders, and thyroid concerns. However, tirzepatide was preferred over semaglutide based on fewer reported side effects overall.
Tirzepatide showed additional advantages: it promoted bone formation (a protective effect) and demonstrated renal protective effects, specifically in decreasing albuminuria and slowing estimated glomerular filtration rate (eGFR) decline — markers of kidney disease progression. These advantages may be related to the additional GIP receptor activation that tirzepatide provides beyond GLP-1 agonism alone.
Fahim, Sally A; Attia, Yasmin M; Messiha, Albeir; Nabawy, Ashrakat Y; Refaat, Fady; El-Maadawy, Walaa H ·
RPEP-10886 · 2025In PACAP knockout male mice, GnRH neuron numbers and immunoreactivity were reduced in the medial preoptic area. Paradoxically, kisspeptin neuron numbers were elevated in both the RP3V and arcuate nucleus, along with increased estrogen receptor alpha (ERα) expression. The medial preoptic area showed fewer androgen receptor-positive cells but more ERα-positive cells, suggesting a disrupted balance between estrogenic and androgenic signaling. These neuroendocrine changes likely underlie the reproductive dysfunction observed in PACAP-deficient males.
Faludi, Péter; Barabás, Klaudia; Lengyel, Ferenc; Udvarácz, Ildikó; Pham, Dániel; Kisjós, Olivér; Nagy, Zsuzsanna; Reglődi, Dóra; Kovács, Gergely ·
RPEP-10888 · 2025The antimicrobial peptide C-1b(3-13) from frog skin suppressed atherosclerosis through a specific molecular mechanism: it upregulated miR-590-5p, which directly targeted and inhibited KLF12 expression, reducing nuclear p300 accumulation and subsequently blocking NF-κB inflammatory signaling.
In ox-LDL-induced foam cells, miR-590-5p significantly suppressed pro-inflammatory cytokine secretion. In ApoE-/- atherosclerosis mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, suppressed inflammatory responses, and shifted macrophage polarization (reducing pro-inflammatory CD68+ M1 macrophages within plaques). The full signaling axis was validated through miRNA sequencing, dual-luciferase reporter assays, and RNA immunoprecipitation.
Fan, Fan; Li, Meng-Miao; Qiu, Zhong-Peng; Li, Zhen-Jia; Shang, De-Jing ·
RPEP-10889 · 2025In 80 hospitalized type 2 diabetes patients, semaglutide (added to metformin) produced significantly better glycemic control than insulin aspart after three months. The semaglutide group achieved lower fasting blood glucose (6.13±0.68 vs. control, P<0.05) and 2-hour postprandial glucose (9.01±0.53 mmol/L vs. control, P<0.05). Patients on semaglutide reached target blood glucose faster (3.88±0.69 days vs. 5.73±1.01 days, P<0.05). Beyond glucose control, semaglutide lowered endothelin-1 (a vasoconstrictor), improved flow-mediated vasodilation (FMD), and improved insulin resistance as measured by HOMA-IR. C-peptide levels — a marker of the pancreas's own insulin production — were also assessed as part of the metabolic panel.
Fan, Pengxiang; Ma, Xiaojun ·
RPEP-10896 · 2025This narrative review synthesizes epidemiologic evidence suggesting that GLP-1 receptor agonist use may be associated with decreased prostate cancer risk. The authors examine how lifestyle interventions affect men with prostate cancer, the relationship between GLP-1 RA use and prostate cancer risk, and potential mechanisms of action on tumor biology. The review provides the rationale for a planned prospective clinical trial evaluating GLP-1 RA effects on prostate cancer.
Fang, Andrew; Frigo, Daniel E; Hahn, Andrew; Razouki, Zayd; Hwang, Jessica; Koutroumpakis, Efstratios; Lawen, Tarek; Smith, Matthew; Hamilton-Reeves, Jill; DiGiovanni, John; Higgason, Noel; Garcia, Rebekka S; Chapin, Brian F; Pettaway, Curtis; Chery, Lisly; Troncoso, Patricia; Logothetis, Christopher; Daniel, Carrie R; Wei, Peng; Gregg, Justin R · Review
RPEP-10910 · 2025GLP-1RA recipients showed significantly greater reductions in AUDIT-C drinking scores compared to both unexposed individuals (DiD: 0.09, P=0.0025) and DPP-4I recipients (DiD: 0.11, P=0.0002). The effects were dramatically larger in people with baseline alcohol use disorder (GLP-1RA vs DPP-4I: DiD 0.65, P<0.0001) and hazardous drinking (GLP-1RA vs DPP-4I: DiD 1.00, P<0.0001).
DPP-4 inhibitor recipients showed no difference from unexposed individuals. Animal experiments confirmed this: neither linagliptin nor omarigliptin reduced binge-like drinking in mice or alcohol self-administration in alcohol-dependent rats, despite successfully lowering blood glucose — confirming target engagement. This convergent human-animal evidence indicates the alcohol-reducing effect requires direct GLP-1 receptor agonism.
Farokhnia, Mehdi; Tazare, John; Pince, Claire L; Bruns, Nicolaus; Gray, Joshua C; Lo Re, Vincent; Fiellin, David A; Kranzler, Henry R; Koob, George F; Justice, Amy C; Vendruscolo, Leandro F; Rentsch, Christopher T; Leggio, Lorenzo ·
RPEP-10912 · 2025The study yielded several key findings across multiple experiments:
- Clinical evaluation of 180 subjects identified the earliest aging signs as uneven skin tone, fine lines, and roughness, with aging turning points in the mid-twenties for lighter skin types and mid-thirties for darker skin types
- Younger skin cells produced more reactive oxygen species (ROS) after UV exposure but were also more responsive to treatment
- Acetyl dipeptide-31 amide (AP31) demonstrated anti-inflammatory effects and stimulated production of extracellular matrix components including collagen and elastin in vitro
- A 12-week clinical study of 46 patients showed that a regimen containing AP31, sunscreen, and bakuchiol significantly improved early aging signs and reduced skin glycation index
- Elasticity loss begins in the 20s and collagen content decreases progressively with age
Farris, Patricia; Frey, Cheri; Parsa, Ramine; Miller, Dara; Shyr, Thomas; Li, Wen-Hwa ·
RPEP-10922 · 2025The review synthesizes evidence across three contexts — intrapersonal, social comparison, and social evaluation — showing that oxytocin consistently modulates processes related to self-protection. Proactive strategies influenced by oxytocin include selective information processing and non-cooperation, while reactive strategies include aggression and cognitive distortion.
The framework uniquely explains why oxytocin produces seemingly contradictory effects: both prosocial behavior (when cooperation protects self-image) and antisocial behavior (when aggression defends against self-threats) can serve the same underlying function of self-defense. The authors also delineate how oxytocin and the structurally similar neuropeptide vasopressin contribute differently to self-protection mechanisms.
Feng, Chunliang; Luo, Wenbo; Zhu, Ruida ·
RPEP-10941 · 2025Liraglutide (0.6 mg subcutaneously daily for 5 days) was well tolerated by all 13 hospitalized COVID-19 pneumonia patients, with 100% survival at 30 days. In the non-critical group, plasma soluble CD147 levels decreased at day 5, while critical care patients showed an increase in CD147 between days 0-5.
Non-critical patients also demonstrated improved right and left ventricular function on echocardiography, reduced plasma troponin levels (indicating less cardiac damage), increased CD147 expression on T lymphocytes (potentially enhancing immune function), and reduced plasma IL-8 (an inflammatory chemokine). These divergent patterns between mild and severe cases suggest liraglutide's benefits may be most pronounced when given early in disease, before critical illness develops.
Ferreira, Eloara V M; Oliveira, Rudolf K F; Salomao, Reinaldo; Brunialti, Milena K C; Cardoso, Martyella B A; Chen, Chien-Nien; Zhao, Lan; McCabe, Colm ·
RPEP-10942 · 2025The review identifies a dual relationship between GLP-1 receptor agonists and headache:
**Therapeutic potential:**
- Weight reduction from GLP-1 RAs can improve IIH-related headaches by decreasing cerebrospinal fluid pressure
- Obesity increases migraine risk and chronification; weight loss may reduce migraine burden
- The gut-brain axis connection suggests additional mechanisms through which GLP-1 RAs may influence headache pathways
**Adverse effects:**
- Headache is a recognized side effect of GLP-1 receptor agonist therapy
- The mechanism by which GLP-1 RAs cause headache is not fully understood
The review emphasizes that understanding this dual relationship is important for clinical decision-making in obese patients with headache disorders.
Ferreira, Erika Tavares; Garcia, Leidys Marina Pedrozo; Londero, Renata Gomes ·
RPEP-10943 · 2025The H1GA(D45C)-NBD anticalin conjugate showed a 6-fold increase in fluorescence emission at 546 nm upon binding amyloid-beta peptides, with an ultra-high binding affinity of KD = 1.2 ± 0.8 nM. The sensor maintained its performance in the presence of 5% (w/v) albumin, demonstrating potential for use in complex biological samples. The engineering strategy involved introducing unpaired cysteine residues in the binding loop region and conjugating them with IANBD amide as a solvatochromic fluorophore — a dye whose emission changes based on its chemical environment.
Feuerbach, Anna; Skerra, Arne ·
RPEP-10948 · 2025In this umbrella review of 230 RCTs involving 36,353 participants, CPAP was the most effective treatment for reducing the apnea-hypopnea index (AHI), with a mean difference of -30.7 events/hour. GLP-1 receptor agonists ranked second: tirzepatide reduced AHI by 21.86 events/hour (SMD -0.84, 95% CI -1.01 to -0.68; moderate-certainty evidence). Mandibular advancement devices came third with an AHI reduction of 11.91 events/hour. For quality of life, physical activity showed the greatest improvement (SMD 1.3), while CPAP showed modest benefits. Only 3% of included evidence was high-certainty, with 68% moderate and 35% low.
Figard, Camille; Ben Messaoud, Raoua; Baillieul, Sébastien; Joyeux-Faure, Marie; Destors, Marie; Tamisier, Renaud; Khouri, Charles; Pépin, Jean-Louis ·
RPEP-10952 · 2025The review establishes that porcine β-defensins (pBDs) have dual functionality: direct antimicrobial activity against a range of pathogens and immunomodulatory properties that enhance the broader immune response. Two approaches to enhancing pBD expression have shown promise: dietary supplementation (specific feed components can upregulate defensin production) and gene editing techniques in pigs and porcine cell models.
The biological roles of pBDs extend beyond simple pathogen killing to include immune cell recruitment, modulation of inflammatory responses, and coordination of adaptive immunity. Clinical trials in swine have validated their efficacy in infection control, supporting their potential as prophylactic and therapeutic alternatives to conventional antibiotics in both veterinary and translational medicine.
Finatto, Arthur Nery; Meurens, François; de Oliveira Costa, Matheus ·
RPEP-10953 · 2025In a vehicle-controlled study of 20 alcohol-preferring male vervet monkeys, semaglutide (0.05 mg/kg twice weekly subcutaneously) significantly reduced voluntary alcohol intake compared to placebo during a 4-week alcohol access period (4 hours daily, Monday through Friday).
Crucially, there were no signs of emetic events (vomiting or nausea), and water intake was not affected — two important controls suggesting that the reduction in alcohol drinking was not simply due to the monkeys feeling sick or reducing all fluid consumption. The study included a 2-week dose escalation period before alcohol was reintroduced and a 1-week washout period at the end.
Fink-Jensen, Anders; Wörtwein, Gitta; Klausen, Mette Kruse; Holst, Jens Juul; Hartmann, Bolette; Thomsen, Morgan; Ptito, Maurice; Beierschmitt, Amy; Palmour, Roberta M ·
RPEP-10954 · 2025In healthy pig heart cells, NPY alone stimulated L-type calcium current via Y1/Gq signaling, while NPY in the presence of norepinephrine had an inhibitory effect via Y2/Gi signaling. Following chronic myocardial infarction, the stimulatory Y1-mediated effect was absent in both remote and border zone myocytes. The inhibitory Y2-mediated effect was absent in remote area myocytes but remained intact in border zone cells. This regional heterogeneity in NPY responsiveness could create electrical gradients across the infarcted heart that promote arrhythmias.
Fiore, Chase M; Agarwal, Shailesh R; Elasoru, Seyi E; Ardell, Jeffrey; Ajijola, Olujimi; Shivkumar, Kalyanam; Harvey, Robert D ·
RPEP-10963 · 2025The review establishes mRNA as an ideal platform for personalized neoantigen cancer immunotherapy due to its versatility and rapid development potential. Key neoantigen selection criteria include: peptide presentation on HLA molecules, HLA-peptide binding affinity, and T cell receptor recognition — all assessed through advanced computational algorithms using next-generation sequencing data. The review covers both shared antigens (common across patients) and individual neoantigens (unique to each patient's tumor), discussing the computational workflows, design considerations for immunogenicity and stability, and clinical trial evidence supporting this approach.
Floudas, Charalampos S; Sarkizova, Siranush; Ceccarelli, Michele; Zheng, Wei ·
RPEP-10969 · 2025Semaglutide suppressed voluntary wheel running in both lean and obese mice — and this wasn't just because the mice were eating less. In a progressive ratio task (where mice had to work harder and harder to access the running wheel), semaglutide-treated mice showed reduced motivation to exert effort for exercise.
Real-time dopamine measurements using fiber photometry revealed that semaglutide amplified dopamine dynamics in the nucleus accumbens (the brain's reward center) at the start and end of running bouts. This suggests semaglutide doesn't just suppress appetite — it alters the brain's reward circuitry in ways that reduce motivation for non-food activities like exercise.
Foscue, Ethan P; Trinko, Joseph R; Jiménez, Jaysen Lara; Kong, Edward; Thompson, Summer L; Stankewich, Kiera; Corstens, Anouk M; Serlie, Mireille J; Taylor, Jane R; DiLeone, Ralph J · Animal
RPEP-10971 · 2025At week 56, liraglutide 3.0mg daily produced significantly better outcomes than placebo:
- BMI change: -5.8% vs +1.6% (difference: -7.4 percentage points, P<0.001)
- Body weight change: +1.6% vs +10.0% (difference: -8.4 percentage points, P=0.001)
- ≥5% BMI reduction: 46% vs 9% (adjusted OR 6.3, P=0.02)
Note that children in both groups gained weight (they're growing), but liraglutide children gained dramatically less. Adverse events were similar overall (89% vs 88%), but GI events were higher with liraglutide (80% vs 54%). Serious adverse events: 12% liraglutide vs 8% placebo.
Fox, Claudia K; Barrientos-Pérez, Margarita; Bomberg, Eric M; Dcruz, John; Gies, Inge; Harder-Lauridsen, Nina M; Jalaludin, Muhammad Yazid; Sahu, Kushal; Weimers, Petra; Zueger, Thomas; Arslanian, Silva ·
RPEP-10975 · 2025Rimegepant 75 mg taken every other day during the perimenstrual window prevented anticipated migraine attacks in 17 out of 20 treatment cycles (85%), with no adverse events reported. However, the picture was more nuanced: only one patient (20%) achieved a sustained reduction in total monthly migraine days. Three patients (60%) experienced a 'temporal displacement' phenomenon, where migraine attacks that were prevented during the perimenstrual window reappeared 3–7 days after menstruation ended.
All five patients reported high satisfaction with perimenstrual symptom control despite the displacement effect, suggesting that even shifting migraines away from the most symptomatic period provided meaningful clinical benefit.
Frank, Florian; Schiefecker, Alois; Kaltseis, Katharina; Eller, Michael; Broessner, Gregor ·
RPEP-10977 · 2025GLP-1 receptor agonists affect gastrointestinal function primarily by slowing gastric emptying and gut transit, which directly contributes to their most common adverse events including nausea, vomiting, and gastroparesis-like symptoms.
A key safety concern highlighted is gastric food retention caused by GLP-1RAs, which increases the risk of pulmonary aspiration during procedures requiring anesthesia. This has prompted changes to pre-anesthesia guidelines for patients taking these medications.
The review also identifies associations between GLP-1RA use and extraintestinal complications including biliary tract disease and pancreatitis. Importantly, current management recommendations — including dosing adjustments, dietary modifications, and pharmacotherapy for GI symptoms — are described as empiric rather than evidence-based.
Frazier, Rosita D; Hasler, William L ·
RPEP-10979 · 2025This is a clinical trial protocol — no results are reported yet. The study design is:
- Phase II randomized, double-blind, placebo-controlled trial
- 200 participants with treatment-refractory OUD (100 on buprenorphine, 100 on methadone)
- Intervention: semaglutide (GLP-1 RA) vs. placebo added to existing MOUD
- Primary outcomes: probability of opioid abstinence, craving measures, days of drug use
- Assessment: urine toxicology screens and self-report across 19 weeks (12 treatment weeks + washout + follow-up)
- Registered: ClinicalTrials.gov NCT06548490
Freet, Christopher S; Shuler, Kirsten; Kawasaki, Sarah; Weintraub, Eric; Greenblatt, Aaron; Kladney, Mat; Nunes, Edward; Foster, Katrina L; Kong, Lan; Raja-Khan, Nazia; Cleveland, H Harrington; Grigson, Patricia S; Bunce, Scott C; Brick, Timothy R; Nyland, Jennifer E ·
RPEP-10983 · 2025GLP-1 patients had significantly higher albumin (4.0 vs 3.6 g/dL, p=0.021) and prealbumin levels (23.2 vs 18.9 mg/dL, p=0.003) than bariatric surgery patients, indicating superior nutritional status. The overall complication rate trended lower in GLP-1 patients (20% vs 40%, OR 0.38), though this did not reach statistical significance (p=0.301) in this 40-patient study.
After multivariable adjustment controlling for weight loss magnitude, duration, albumin, and pannus weight, the direction of effect continued to favor GLP-1 patients (adjusted OR 0.72, p=0.830). GLP-1 patients had less total weight loss (29.9 vs 47.2 kg, p<0.001), which may partly explain the better outcomes.
Friedman, Or; Tal, Daniel ·
RPEP-10989 · 2025Combining leptin and liraglutide (a GLP-1 receptor agonist) normalized blood glucose levels in mice with insulin-dependent diabetes — achieving glucose control comparable to healthy mice, without any insulin treatment.
Each peptide worked on its own: both leptin monotherapy and liraglutide monotherapy significantly improved blood glucose levels and glucose tolerance compared to untreated diabetic mice. But the combination (LEP+LIRA) outperformed either alone, restoring glucose metabolism to levels indistinguishable from healthy control mice.
Fu, Linlin; Sugiyama, Mariko; Kamal, Shahriar; Ide, Tsubasa; Takeda, Tadashi; Kuno, Mitsuhiro; Takagi, Hiroshi; Koike, Teruhiko; Arima, Hiroshi; Banno, Ryoichi · Animal Study
RPEP-11001 · 2025The brain-gut regulation of intestinal barrier function involves two distinct mechanisms — one dependent on the spleen and one independent. When neuropeptides orexin, ghrelin, or oxytocin are injected into the brain, they improve intestinal barrier function through a pathway that requires the spleen. However, GLP-1 (via liraglutide) acts through a separate spleen-independent pathway via vagal cholinergic signaling.
In splenectomized rats, orexin, ghrelin, and oxytocin lost their ability to reduce gut permeability, while liraglutide maintained its dose-dependent protective effect through atropine-sensitive (cholinergic) vagal mechanisms.
Funayama, Takuya; Nozu, Tsukasa; Ishioh, Masatomo; Igarashi, Sho; Tanaka, Hiroki; Sumi, Chihiro; Saito, Takeshi; Toki, Yasumichi; Hatayama, Mayumi; Yamamoto, Masayo; Shindo, Motohiro; Takahashi, Shuichiro; Okumura, Toshikatsu · Animal
RPEP-11002 · 2025After 32 weeks of weekly subcutaneous semaglutide (1.0 mg), participants showed significant reductions in C-reactive protein (CRP), interleukin-6 (IL-6), and soluble CD163 (sCD163) compared to baseline — all markers strongly linked to cardiovascular risk and mortality in people with HIV. Soluble CD14 showed a trend toward reduction (P = .08). Importantly, monocyte proportions and T-cell phenotypes remained unchanged, suggesting the anti-inflammatory effect operates through pathways other than direct immune cell modulation.
Funderburg, Nicholas T; Ross Eckard, Allison; Wu, Qian; Sattar, Abdus; Ailstock, Kate; Cummings, Morgan; Labbato, Danielle; McComsey, Grace A ·
RPEP-11008 · 2025The review highlights the paradigm shift in obesity pharmacotherapy driven by peptide-based drugs:
- Semaglutide: first obesity drug to demonstrate a significant 20% reduction in major adverse cardiovascular events (MACE) in the SELECT trial, though secondary endpoints were neutral
- Tirzepatide and retatrutide: next-generation multi-receptor agonists achieving up to 24% weight loss
- These drugs exert pleiotropic effects beyond weight loss: anti-inflammatory properties, improved endothelial function, and anti-atherosclerotic effects that may contribute to cardiovascular protection
- Lifestyle modifications, while foundational, have limited long-term efficacy as most individuals regain lost weight
- Bariatric surgery remains most effective for long-term weight management but has limited accessibility
Gajos, Grzegorz ·
RPEP-11013 · 2025Across the pooled SURPASS-1 through -5 trial data (3,559 participants), 58.9% of tirzepatide-treated adults with type 2 diabetes shifted to an improved (lower) BMI category at weeks 40-52, while 41.1% remained in the same or a worsened category.
Participants who improved their BMI category showed numerically larger mean improvements from baseline in the majority of selected cardiometabolic parameters across all five trials compared to those who did not improve. Weight-related patient-reported outcomes were also numerically best in the improved BMI group, suggesting that meaningful BMI category shifts translate to both objective health improvements and subjective quality-of-life benefits.
Galindo, Rodolfo J; Lee, Clare J; Allen, Sheryl Elaine; Dib, Anne; Boye, Kristina S; Thieu, Vivian Thuyanh; Dong, Wenxiu; Sapin, Hélène; Wiese, Russell J ·
RPEP-11018 · 2025Both GLP-2 and GIP independently increased blood flow through the superior mesenteric artery (the main blood vessel feeding the intestines) in anesthetized rats. Surprisingly, this effect did not depend on nitric oxide or vasoactive intestinal peptide — two of the most commonly assumed mediators of gut blood flow. Combining the two peptides or using a novel dual GIP/GLP-2 co-agonist did not produce a synergistic (greater-than-additive) effect. The GLP-2 receptor antagonist GLP-2(3-33) successfully blocked GLP-2's blood flow effect, confirming it acts through the GLP-2 receptor.
Galsgaard, Katrine D; Hartmann, Bolette; Rosenkilde, Mette M; Holst, Jens J; Gasbjerg, Lærke S; Sørensen, Charlotte M ·