RPEP-08834 · 2024Using liquid chromatography tandem mass spectrometry — a highly specific measurement technique — the researchers analyzed NPY, its precursors, and metabolites in plasma and tissue from 181 patients. NPY and related peptides were less accurate than PSA alone at diagnosing significant prostate cancer.
Combining multiple NPY-related peptides in a stepwise diagnostic approach did not improve diagnostic performance in a way that would benefit patients. There was a limited signal suggesting NPY might add value for patients with PSA in the 4–9 ng/ml gray zone, but this finding lacked statistical strength.
Maurer, Jonathan; Eugster, Philippe J; Collins, Kiana; Vocat, Céline; Oke, Jason; Nicholson, Brian; Rakauskas, Arnas; Grouzmann, Eric; Valerio, Massimo ·
RPEP-08839 · 2024The review covers three main categories of nanocarriers for bioactive peptide delivery:
1. **Lipid-based nanocarriers** (liposomes, solid lipid nanoparticles, nanoemulsions) — protect peptides from gastric degradation and enhance absorption through intestinal membranes.
2. **Carbohydrate-based nanocarriers** (chitosan, alginate, starch nanoparticles) — provide pH-responsive release and mucoadhesive properties for targeted gut delivery.
3. **Protein-based nanocarriers** (casein, whey, zein) — offer food-grade compatibility and controlled release.
Across all types, nanoencapsulation improved peptide stability, solubility, resistance to gastric digestion, and bioavailability while reducing or masking undesirable flavors — the key barriers to incorporating bioactive peptides into functional foods and dietary supplements.
Mazloomi, Narges; Safari, Barbod; Can Karaca, Asli; Karimzadeh, Laleh; Moghadasi, Shokufeh; Ghanbari, Masoud; Assadpour, Elham; Sarabandi, Khashayar; Jafari, Seid Mahdi ·
RPEP-08845 · 2024NLY01 — a brain-penetrant, pegylated, longer-lasting version of the GLP-1 agonist exenatide — showed NO benefit for Parkinson's disease in this rigorous 36-week trial. Neither the 2.5 mg nor 5.0 mg dose improved motor or non-motor symptoms compared to placebo on the MDS-UPDRS scale (p=0.77 and p=0.79, respectively).
The drug was designed to reduce brain inflammation by suppressing microglial activation, a mechanism distinct from its metabolic effects. Despite strong preclinical rationale and adequate dosing, NLY01 simply did not work for Parkinson's disease symptoms. An exploratory subgroup analysis hinted at possible motor benefit in younger patients, but this requires replication before drawing conclusions. Side effects were predominantly gastrointestinal: nausea affected 39-58% of treated patients versus 19% on placebo.
McGarry, Andrew; Rosanbalm, Shane; Leinonen, Mika; Olanow, C Warren; To, Dennis; Bell, Adam; Lee, Daniel; Chang, Jamie; Dubow, Jordan; Dhall, Rohit; Burdick, Daniel; Parashos, Sotirios; Feuerstein, Jeanne; Quinn, Joseph; Pahwa, Rajesh; Afshari, Mitra; Ramirez-Zamora, Aldolfo; Chou, Kelvin; Tarakad, Arjun; Luca, Corneliu; Klos, Kevin; Bordelon, Yvette; St Hiliare, Marie-Helene; Shprecher, David; Lee, Seulki; Dawson, Ted M; Roschke, Viktor; Kieburtz, Karl · Randomized Controlled Trial
RPEP-08847 · 2024Accidental overdoses with GLP-1 receptor agonists are being reported at disproportionately high rates to the FDA. Across 3,348 reports from 2003 to early 2024, every GLP-1 drug in the class showed significantly elevated reporting odds ratios for accidental overdose:
- ROR range: 2.64 to 61.12 (all statistically significant, p < 0.008)
- Affected drugs: semaglutide, dulaglutide, exenatide, liraglutide, and tirzepatide
The authors link this to patients accessing GLP-1 drugs through online and compounding pharmacies due to cost and availability barriers, with the greatest risk falling on racial, ethnic, and socioeconomically disadvantaged populations.
McIntyre, Roger S; Kwan, Angela T H · Observational
RPEP-08848 · 2024Psychotropic drug-related weight gain (PDWG) is a major barrier to psychiatric treatment adherence. The review found:
- Differential weight gain liability exists across antipsychotics, antidepressants, and anticonvulsants, and newer agents with lower liability should be prioritized
- Lithium's weight gain effect is lower than previously thought
- Lifestyle modification is effective and comparable to general population results
- Metformin is the most-studied pharmacological treatment for both prevention and treatment of PDWG
- GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) show promising emerging data
- Most other pharmacologic antidotes (topiramate, H2 antagonists) have only low-confidence evidence
- Future research priorities include large trials of GLP-1 RAs and tirzepatide in psychiatric populations
McIntyre, Roger S; Kwan, Angela T H; Rosenblat, Joshua D; Teopiz, Kayla M; Mansur, Rodrigo B ·
RPEP-08849 · 2024Semaglutide and liraglutide showed disproportionate reporting of suicidal ideation and 'depression/suicidal' events in the FDA Adverse Event Reporting System, with reporting odds ratios whose lower 95% confidence interval exceeded 1.0 (indicating statistical significance).
Critically, no disproportionate reporting of more severe outcomes — suicidal behavior, suicide attempts, or completed suicide — was observed for any FDA-approved GLP-1 receptor agonist. When the data was evaluated using Bradford Hill criteria for causality and confounding factors were considered, the researchers found no causal link between GLP-1 RAs and suicidality.
McIntyre, Roger S; Mansur, Rodrigo B; Rosenblat, Joshua D; Kwan, Angela T H ·
RPEP-08850 · 2024Calorie restriction increased chromogranin A-positive endocrine cells, including ghrelin-producing cells, in mouse stomachs. This expansion was driven by Notch-dependent signaling that activates FOXO1, which promotes a specific subpopulation of endocrine progenitor cells (FOXO1/Neurog3+) to proliferate and differentiate. Blocking Notch with gamma-secretase inhibitors reversed the effect. Uniquely, calorie restriction decreased Lgr5+ stem cells in the stomach (opposite to its effect in the intestine) while increasing endocrine progenitors. FOXO1 activation alone was sufficient to promote endocrine cell differentiation even without Notch signaling. Tirzepatide also expanded ghrelin-producing cells in mice.
McKimpson, Wendy M; Spiegel, Sophia; Mukhanova, Maria; Kraakman, Michael; Du, Wen; Kitamoto, Takumi; Yu, Junjie; Deng, Zhaobin; Pajvani, Utpal; Accili, Domenico ·
RPEP-08860 · 2024Average weight loss was 5.81 ± 2.64 kg at 3 months and 9.86 ± 3.54 kg at 6 months. Weight loss was similar in patients with and without type 2 diabetes. Significant reductions were observed in HbA1c, BMI, and cholesterol levels (all p<0.001). By 6 months, 40% of patients remained on 0.5 mg, 33.8% escalated to 1 mg, and 24.6% reached 2 mg weekly. Adverse effects were reported by 55.4% at 3 months but declined to 34.5% at 6 months, with most being mild-to-moderate GI symptoms. Only 1.5% reduced their dose due to side effects.
Memon, Muhammad Y; Ahsan, Tasnim; Jabeen, Rukhshanda; Latif, Saba; Qasim, Saeeda F; Imran, Paras ·
RPEP-08869 · 2024In 50 male diabetic rats across five groups, all three interventions significantly improved body weight, BMI, blood glucose, insulin, lipid profiles, and atherogenic indices compared to untreated diabetic controls.
Key differentiators:
- **Beta-cell regeneration**: Liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 (a cell proliferation marker) in the pancreas, indicating beta-cell regeneration. Naltrexone/bupropion (NTX+BUP) showed no significant regenerative effect.
- **Beta-arrestin-1**: Liraglutide significantly decreased beta-arrestin-1 levels compared to both NTX+BUP and caloric restriction — a unique molecular signature.
- **Weight loss**: NTX+BUP and caloric restriction produced greater weight loss than liraglutide, yet liraglutide was superior for beta-cell outcomes.
Merzeban, Dina H; El Amin Ali, Amani M; Hammad, Reem O; Elmahdi, Mohamed H; Sofi, Marwa A; Mahmoud, Rania H; Metwally, Sayed M; El Ebiary, Ahmed M ·
RPEP-08871 · 2024In a rat transient middle cerebral artery occlusion (tMCAO) stroke model, semaglutide treatment produced multiple neuroprotective effects:
- Decreased neurological deficit scores on days 1, 3, and 7 post-intervention
- Reduced cerebral infarct volume (measured by TTC staining)
- Decreased CD68 expression (marker of pro-inflammatory M1 microglial activation)
- Decreased TNF-α levels (pro-inflammatory cytokine)
- Increased CD206 expression (marker of anti-inflammatory M2 microglial activation)
- Increased TGF-β levels (anti-inflammatory mediator)
- Reduced P65 levels in the NF-κB signaling cascade
The mechanism involves semaglutide promoting microglial phenotype transformation from M1 (neurotoxic) to M2 (neuroprotective) while inhibiting NF-κB-driven inflammation.
Mi, Rulin; Cheng, Huifeng; Chen, Rui; Bai, Bo; Li, An; Gao, Fankai; Xue, Guofang ·
RPEP-08872 · 2024LL-37, the only human cathelicidin antimicrobial peptide, has been found to regulate multiple cardiovascular processes beyond its traditional antimicrobial role:
- Atherosclerosis regulation — LL-37 influences plaque formation and stability in blood vessels
- Thrombosis modulation — the peptide affects blood clot formation
- Inflammatory response control — LL-37 modulates cardiac inflammatory pathways
- Cardiac hypertrophy regulation — the peptide influences heart muscle thickening
Engineered LL-37-related peptides have been developed and shown to regulate disease progression in experimental models, demonstrating potential for clinical application in cardiovascular disease.
Miao, Shuo; Liu, Houde; Yang, Qingyu; Zhang, Yaping; Chen, Tao; Chen, Shuai; Mao, Xin; Zhang, Qingsong ·
RPEP-08889 · 2024For people with obesity but not diabetes, the benefits of GLP-1 agonists clearly outweighed the harms — but only if you're aiming for 10% or more weight loss. Among 1,000 people treated for 2 years, 375 more achieved 10% weight loss compared to placebo, with a 97% probability of net benefit at year 1 and 91% at year 2.
However, aiming for just 5% weight loss did NOT show a net benefit (only 1% probability at year 2) because the cumulative side effects — nausea, vomiting, constipation, diarrhea, hair loss, gallstones — outweighed the modest weight loss. Among the drugs, semaglutide had the highest net benefit probability (96% at 2 years), followed by liraglutide (72%) and tirzepatide (60%). The study emphasizes that treatment decisions must be personalized based on individual goals and willingness to tolerate side effects.
Moll, Hannah; Frey, Eliane; Gerber, Philipp; Geidl, Bettina; Kaufmann, Marco; Braun, Julia; Beuschlein, Felix; Puhan, Milo A; Yebyo, Henock G · Meta Analysis
RPEP-08892 · 2024CGRP inhibitors are established as safe and effective for adult migraine treatment, and their use may be appropriate for pediatric patients in certain clinical situations. The review describes migraine pathophysiology as it relates to CGRP, provides an overview of available CGRP-targeting medications (both monoclonal antibodies and small-molecule antagonists), and discusses clinical usage considerations for children and adolescents. The limited evidence base for this population is a key theme.
Moore, Lisa; Pakalnis, Ann ·
RPEP-08896 · 2024A 56-year-old female patient with class 3 obesity developed well-defined, round, erythematous pruriginous (itchy) plaques surrounding the injection site approximately 24 hours after each liraglutide (Saxenda) administration, beginning one month after starting treatment.
The delayed-type hypersensitivity reaction was confirmed through allergy testing and histopathological examination of the skin lesions. Despite this reaction to liraglutide, the patient tolerated semaglutide without hypersensitivity, indicating that the allergenic component was specific to liraglutide rather than common to all GLP-1 receptor agonists.
Moreno-Borque, Ricardo; Guhl-Millán, Guillermo; Mera-Carreiro, Sara; Pazos-Guerra, Mario; Cortés-Toro, Jose Antonio; López-Bran, Eduardo ·
RPEP-08899 · 2024At 26 weeks, dulaglutide 1.5 mg was statistically superior to 0.75 mg for HbA1c reduction (LSM difference -0.29%, 95% CI: -0.43 to -0.14). At 52 weeks, the higher dose showed a significantly greater proportion reaching HbA1c <7.0% (46.3% vs 38.5%, p = 0.03) and greater fasting glucose reduction (LSM difference -9.4 mg/dL, 95% CI: -14.4 to -4.3, p < 0.001).
No statistically significant body weight change was observed in either arm. The most common adverse events were constipation (11.3%), diarrhea (9.6%), and fever (9.0%). Overall, 75.4% of participants experienced at least one treatment-emergent adverse event.
Morioka, Tomoaki; Takeuchi, Masakazu; Ozeki, Akichika; Emoto, Masanori ·
RPEP-08902 · 2024Researchers developed cLF36, a chimeric 42-amino acid peptide combining the complete camel lactoferrampin sequence with a partial lactoferricin sequence. Testing across multiple platforms showed broad-spectrum antimicrobial activity against human, avian, and plant bacterial pathogens. The peptide also demonstrated antiviral effects against hepatitis C virus, influenza virus, and rotavirus in computational and in vitro studies.
Notably, cLF36 showed selective anticancer activity — higher toxicity against tumor cell lines than normal cells, potentially because it targets negatively charged glycosaminoglycans on tumor cell surfaces. The peptide showed no toxicity to host cells and demonstrated strong thermal and protease stability in serum, suggesting practical durability.
Morovati, Solmaz; Baghkheirati, Amir Asghari; Sekhavati, Mohammad Hadi; Razmyar, Jamshid · Review
RPEP-08905 · 2024The review identifies that GLP-1 receptors are expressed on multiple types of intraepithelial lymphocytes in the gut, including natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ and TCRαβ+CD8αβ+) populations. Both the body's own GLP-1 signaling and pharmacological GLP-1R activation influence local gut inflammation, systemic inflammation, the gut microbiome, whole-body metabolism, and GLP-1 bioavailability itself.
GIPR signaling has been shown to affect the production of blood cells from bone marrow (hematopoiesis), but its specific role in gut immune function remains poorly understood. The authors also highlight a significant gap in the literature regarding how biological sex influences these signaling pathways.
Morrow, Nadya M; Morissette, Arianne; Mulvihill, Erin E ·
RPEP-08915 · 2024In non-diabetic rats (n=10 per group):
- All drugs (empagliflozin, canagliflozin, dulaglutide) reduced brain infarct size more effectively than metformin
- Dulaglutide improved neurological status better than both metformin and SGLT2 inhibitors
- All drugs reduced neurofilament light chains (NLC) and neuronal damage markers; none reduced glial marker S100BB
In diabetic rats:
- All drugs had infarct-limiting effects and reduced neurological deficits
- Untreated diabetic rats had the worst neurological outcomes
- Dulaglutide and empagliflozin (but not canagliflozin) also decreased the glial damage marker S100BB
- None affected neuron-specific enolase
Conclusion: GLP-1RA may be more neuroprotective than SGLT2i overall, with benefits on both neuronal and glial damage.
Murasheva, Anna; Fuks, Oksana; Timkina, Natalya; Mikhailova, Arina; Vlasov, Timur; Samochernykh, Konstantin; Karonova, Tatiana ·
RPEP-08916 · 2024The GHRH receptor antagonist peptide MIA-690 showed synergistic antitumor effects when combined with the EGFR inhibitor gefitinib in castration-resistant prostate cancer (CRPC) PC-3 cells. The combination inhibited cell viability, adhesion, and metalloprotease activity more effectively than either agent alone, and induced cell cycle arrest. These effects were confirmed in vivo in nude mice bearing PC-3 tumors 36 days after inoculation, demonstrating that blocking GHRH-R/EGFR crosstalk is a viable strategy against treatment-resistant prostate cancer.
Muñoz-Moreno, Laura; Gómez-Calcerrada, M Isabel; Arenas, M Isabel; Carmena, M José; Prieto, Juan C; Schally, Andrew V; Bajo, Ana M ·
RPEP-08918 · 2024During acute abstinence (1 day), male mice had upregulated NPY, somatostatin (Sst), and NPY receptor Y2 (Npy2r) in the CeA, while females showed upregulated GABA receptor subunit alpha 2 (Gabra2) and the peptidase angiotensinase C (Prcp). Males also had downregulated NMDA receptor subunit Grin1.
During protracted abstinence (7 days), male mice maintained elevated Npy2r, NPY, and somatostatin expression. Female mice showed increased corticotropin-releasing hormone (CRH) and NPY expression. The gene expression profiles differed significantly between sexes at both time points, suggesting sex-specific neuropeptide responses to binge alcohol exposure and withdrawal.
Méndez, Hernán G; Neira, Sofia; Flanigan, Meghan E; Haun, Harold L; Boyt, Kristen M; Thiele, Todd E; Kash, Thomas L ·
RPEP-08920 · 2024Across seven RCTs (n=5,140), the overall placebo-subtracted weight loss was 15.0% (95% CI: -17.8 to -12.2). When broken down by drug:
- Semaglutide 2.4 mg weekly (5 studies, n=3,288): -12.9% weight loss (95% CI: -14.7 to -11.1), -9.7 cm waist circumference reduction (95% CI: -10.8 to -8.5)
- Tirzepatide 10 or 15 mg weekly (2 studies, n=1,852): -19.2% weight loss (95% CI: -22.2 to -16.2), -14.6 cm waist circumference reduction (95% CI: -15.8 to -13.4)
Adverse events were primarily gastrointestinal, mild to moderate in severity, most frequent during dose titration, and leveled off during maintenance treatment.
Müllertz, Alberte Laura Oest; Sandsdal, Rasmus Michael; Jensen, Simon Birk Kjær; Torekov, Signe Sørensen ·
RPEP-08929 · 2024LL37 enhanced LDL uptake in macrophages through three receptors: LDLR, SR-B1, and CD36. This increased cytosolic cholesterol in macrophages and altered lipid metabolism gene expression in ways consistent with cholesterol overloading — the key process driving foam cell formation and atherosclerotic plaque development.
Structural analysis using synchrotron x-ray scattering revealed how LL37 binds LDL particles and facilitates receptor interactions. Critically, this LDL uptake function is unique to human and some primate cathelicidins — it was not observed with mouse or rabbit versions of the peptide, which may explain why standard animal models haven't captured this mechanism. ApoE-knockout mice engineered to express human LL37 developed larger atherosclerotic plaques than controls. In humans with cardiovascular disease, plasma LL37 levels positively correlated with oxidized phospholipids on apolipoprotein B — a validated biomarker of atherosclerotic disease.
Nakamura, Yoshiyuki; Kulkarni, Nikhil N; Takahashi, Toshiya; Alimohamadi, Haleh; Dokoshi, Tatsuya; Liu, Edward; Shia, Michael; Numata, Tomofumi; Luo, Elizabeth Wc; Gombart, Adrian F; Yang, Xiaohong; Secrest, Patrick; Gordts, Philip Lsm; Tsimikas, Sotirios; Wong, Gerard Cl; Gallo, Richard L ·
RPEP-08931 · 2024Three patients with AVP deficiency (diabetes insipidus) who were on stable desmopressin therapy needed to reduce their desmopressin doses after starting GLP-1 receptor agonists for diabetes or obesity. The GLP-1 drugs decreased thirst perception and altered sodium and water handling, effectively enhancing the effects of their existing desmopressin therapy.
The proposed mechanism: GLP-1 RAs induce natriuresis (increased sodium excretion) and increase distal fluid delivery to the kidneys' collecting ducts. In patients with AVP deficiency taking desmopressin, this means the same dose of desmopressin now concentrates urine more effectively — requiring a lower dose to maintain normal water balance. All three patients maintained normal thirst and urine output on the reduced desmopressin doses.
Nakhleh, Afif; Shehadeh, Naim; Mansour, Bshara · Case Series
RPEP-08933 · 2024Among 811 adults with type 2 diabetes at an Australian specialist diabetes clinic, median HbA1c levels significantly increased by 0.3% during a period when GLP-1 receptor agonist medications were in short supply. The analysis covered prescriptions from January 2019 through October 2023, comparing outcomes before and during the shortage period.
A 0.3% rise in HbA1c is clinically meaningful — it reflects worsening blood sugar control that, if sustained, increases the risk of diabetes-related complications including cardiovascular disease, kidney damage, and nerve problems.
Nanayakkara, Natalie; Lh Huang, Michael; Jenkins, Alicia J; Cohen, Neale D ·
RPEP-08944 · 2024Semaglutide produced a concentration- and time-dependent positive inotropic effect (increased contraction force) in isolated human right atrial preparations obtained during open-heart surgery. The effect was accompanied by increased rates of tension development and relaxation, plus reduced muscle relaxation time.
Mechanistically, the positive inotropic effect was attenuated by H89 (a cAMP-dependent protein kinase inhibitor) and by ryanodine (an inhibitor of sarcoplasmic calcium release), indicating the effect is mediated through the cAMP/PKA pathway and intracellular calcium handling. Notably, semaglutide up to 100 nM failed to produce a positive inotropic effect in mouse left atrial preparations, highlighting a species-specific response.
Neumann, Joachim; Hadová, Katarína; Klimas, Jan; Hofmann, Britt; Gergs, Ulrich ·
RPEP-08946 · 2024The Axcess oral peptide delivery formulation achieved biopotencies of 9% for exendin-4 and 14.8% for semaglutide in preclinical models — meaning these percentages of the orally administered peptide reached the bloodstream in active form and produced measurable changes in insulin and glucose levels. The oral route delivers peptides to interact with GLP-1 receptors on vagal afferents in the intestine, mimicking how the body's own GLP-1 naturally works.
New, R R C; Bogus, M; Travers, G N; Hahn, U; Vaiceliunaite, A; Burnet, M; Wang, J H; Wen, H ·
RPEP-08950 · 2024Across the SURPASS 1–5 clinical trials, tirzepatide dramatically reduced the proportion of type 2 diabetes patients meeting criteria for metabolic syndrome. At baseline, 67–88% of patients across treatment groups had metabolic syndrome. After treatment, tirzepatide reduced this to 38–64%, compared to 64–82% with comparators (placebo, semaglutide 1 mg, insulin degludec, and insulin glargine).
The reductions were statistically significant at all tirzepatide doses versus all comparators (P<0.001). Every individual component of metabolic syndrome (insulin resistance, abdominal obesity, dyslipidemia, hypertension, hyperglycemia) improved more with tirzepatide. Greater weight loss corresponded to greater metabolic syndrome resolution. Background medication type and gender did not influence the results.
Nicholls, Stephen J; Tofé, Santiago; le Roux, Carel W; D'Alessio, David A; Wiese, Russell J; Pavo, Imre; Brown, Katelyn; Weerakkody, Govinda J; Zeytinoglu, Meltem; Romera, Irene C · Post Hoc Analysis
RPEP-08953 · 2024Stapled peptides represent a significant advancement in peptide drug design for metabolic diseases. By stabilizing the α-helical conformation through chemical cross-links, these peptides gain enhanced stability against enzymatic degradation, improved cellular permeability, and stronger binding affinity for their targets.
The review describes how stapled peptides can function as agonists, antagonists, or dual-agonists by disrupting specific protein-protein interactions in metabolic pathways. Key targets include molecular pathways involved in glucose metabolism, insulin secretion, and food intake regulation. However, challenges remain in optimizing structural stability, controlling peptide helicity, managing isomer mixtures during synthesis, and minimizing potential side effects.
Nielipińska, Dominika; Rubiak, Dominika; Pietrzyk-Brzezińska, Agnieszka J; Małolepsza, Joanna; Błażewska, Katarzyna M; Gendaszewska-Darmach, Edyta ·
RPEP-08962 · 2024Analysis of 22,287 adverse event reports from the FDA's FAERS database revealed distinct side effect profiles depending on whether semaglutide was given by injection or taken orally. Subcutaneous injection was more likely to cause endocrine-related adverse events, while oral semaglutide was more likely to trigger gastrointestinal side effects.
Notably, oral administration also accelerated the onset of adverse reactions compared to injection. The study compared 16,346 subcutaneous injection reports against 2,496 oral administration reports from Q4 2017 through Q4 2023.
Niu, Kaibin; Fan, Maoxia; Gao, Wulin; Chen, Chen; Dai, Guohua · Pharmacovigilance
RPEP-08963 · 2024Rats receiving 10 μg exenatide subcutaneously immediately after spinal cord contusion injury showed significantly higher BBB locomotor scores (measuring hind limb motor function) from day 7 after injury onward compared to controls.
The mechanism involved macrophage polarization: exenatide increased expression of M2 (anti-inflammatory) markers and anti-inflammatory interleukins while decreasing M1 (pro-inflammatory) markers and inflammatory cytokines. Immunohistochemistry confirmed significantly more M2 macrophages in the exenatide group by day 3 after injury, while M1 macrophage numbers did not differ between groups — indicating the drug promoted anti-inflammatory immune cells rather than simply suppressing all immune activity.
Noguchi, Toshihiro; Katoh, Hiroyuki; Nomura, Satoshi; Okada, Keiko; Watanabe, Masahiko ·
RPEP-08965 · 2024Liraglutide at both 47 and 94 μg/kg/day for 4 weeks ameliorated α-PVP-induced spatial learning and memory impairments in the Morris Water Maze. The cognitive recovery was accompanied by restoration of brain mitochondrial function: reduced reactive oxygen species (ROS) formation, restored mitochondrial membrane potential, decreased cytochrome c release, repaired mitochondrial outer membrane damage, reduced mitochondrial swelling, and normalized brain ADP/ATP ratios. These findings demonstrate that liraglutide's neuroprotective effects operate through mitochondrial rescue mechanisms.
Noruzi, Marzieh; Behmadi, Homayoon; Sabzevari, Omid; Foroumadi, Alireza; Ghahremani, Mohammad Hossein; Pourahmad, Jalal; Hassani, Shokoufeh; Baeeri, Maryam; Gholami, Mahdi; Ghahremanian, Amirhosein; Seyfi, Soheila; Taghizadeh, Ghorban; Sharifzadeh, Mohammad ·
RPEP-08968 · 2024Patients with optimal weight loss (OWL) after RYGB had higher basal acylated ghrelin and greater post-meal GLP-1 responses (iAUC) compared to those with suboptimal weight loss (SWL) and controls. OWL patients also had lower post-meal ghrelin responses (iAUC) — meaning ghrelin dropped more after eating, signaling better satiety.
Both surgical groups showed elevated PYY and CCK post-meal responses compared to controls. Prospective food consumption ratings were lower in OWL than SWL. Total weight loss correlated positively with GLP-1 responses and negatively with hunger and desire-to-eat ratings, suggesting gut peptide signaling plays a key role in long-term weight maintenance after surgery.
Nymo, Siren; Lundanes, Julianne; Eriksen, Kevin; Aukan, Marthe; Rehfeld, Jens Frederik; Holst, Jens Juul; Johnsen, Gjermund; Græslie, Hallvard; Kulseng, Bård; Sandvik, Jorunn; Martins, Catia ·
RPEP-08983 · 2024A patient taking a GLP-1 receptor agonist/insulin secretagogue had a nondiagnostic FDG PET scan showing abnormal muscular and myocardial FDG uptake. The altered biodistribution was attributed to the drug's insulin-stimulating mechanism, which redirects glucose uptake to muscle and heart tissue, potentially masking tumor uptake and complicating scan interpretation.
Oldan, Jorge D; Landman, Paula G; Schroeder, Jennifer A; Khandani, Amir H; Solnes, Lilja B; Lee, Carrie B; Rowe, Steven P ·
RPEP-08986 · 2024Anti-CGRP monoclonal antibodies reduced monthly migraine days by 50% in 27.6-61.4% of chronic migraine patients across the reviewed studies. Conversion from chronic to episodic migraine occurred in 40.88% of cases. Between 29-88% of patients who were overusing acute medications successfully stopped. Obesity emerged as the main negative predictor of treatment response. Atogepant became the first gepant (oral CGRP receptor antagonist) to demonstrate significant reduction in monthly migraine days versus placebo. No single anti-CGRP monoclonal antibody showed clear superiority over others.
Oliveira, Renato; Gil-Gouveia, Raquel; Puledda, Francesca ·
RPEP-08998 · 2024From 2007-2023, 187,757 adverse events were reported with GLP-1 RAs in the US, including 16,568 GI-related events. Semaglutide was significantly associated with nausea, vomiting, and delayed gastric emptying. Exenatide was associated with pancreatitis and a significantly elevated death risk (ROR: 4.50).
Dulaglutide and liraglutide were associated with fewer significant GI adverse events compared to semaglutide and exenatide. Semaglutide had the broadest range of notable GI adverse effects among all GLP-1 RAs analyzed.
Osei, Samuel Prince; Akomaning, Edwin; Florut, Teodora Francesca; Sodhi, Mohit; Lacy, Brian E; Aldhaleei, Wafa A; Bhagavathula, Akshaya Srikanth ·
RPEP-08999 · 2024Starting sitagliptin (DPP-4 inhibitor, 50 mg/day) enabled complete insulin discontinuation (from 47 U/day) and reduced HbA1c by 4.8% in a patient with permanent neonatal diabetes on high-dose glibenclamide (0.6 mg/kg/day). Doubling the sitagliptin dose and subsequently switching to semaglutide (GLP-1 receptor agonist, 0.25 then 0.5 mg/week) produced further HbA1c improvements with graded increases in endogenous insulin secretion.
Glibenclamide was safely downtitrated from 0.6 to 0.4 mg/kg/day without hypoglycemia. Continuous glucose monitoring showed improvements in both intra- and inter-day glucose variability, indicating more stable blood sugar control throughout the day.
Oshiro, Ayaka; Aotani, Ryoichiro; Sakamoto, Wakako; Kitazono, Takanari; Ohkuma, Toshiaki ·
RPEP-09004 · 2024Switching from dulaglutide (a single GLP-1 agonist) to tirzepatide (a dual GIP/GLP-1 agonist) in 14 hemodialysis patients with type 2 diabetes significantly improved blood sugar control. Time in range increased from 42.7% to 50.8% (p=0.02), time above range dropped from 48.4% to 37.8% (p=0.02), and mean glucose fell from 156.6 to 137.4 mg/dL (p=0.006). Critically, hypoglycemia did not increase — time below range was statistically unchanged at 11.3% vs 8.9% (p=0.75). Side effects were mild: 21.4% had dyspepsia and 7.1% had nausea, with no serious adverse events.
Otsuka, Emiko; Kitamura, Mineaki; Funakoshi, Satoshi; Mukae, Hiroshi; Nishino, Tomoya ·
RPEP-09005 · 2024Analysis of 37,827 adverse event reports for tirzepatide in the FDA's FAERS database identified 100 statistically significant adverse event signals. The most commonly reported events were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. An unexpected safety signal — starvation ketoacidosis — was identified.
Notably, side effects differed between sexes: men primarily reported gastrointestinal disorders, while women more commonly reported general disorders and injection site reactions. The median time to onset for adverse events was 23 days after starting tirzepatide.
Ou, Yingyong; Cui, Zhiwei; Lou, Siyu; Zhu, Chengyu; Chen, Junyou; Zhou, Linmei; Zhao, Ruizhen; Wang, Li; Zou, Fan · Pharmacovigilance
RPEP-09013 · 2024Neuropeptide Y (NPY) treatment preserved both structural and functional integrity of the inner retina in a mouse model of glaucoma with elevated intraocular pressure. NPY mitigated axonal damage and optic nerve degeneration, reduced inflammatory glial cell activation (decreased GFAP and Iba-1 expression), and restored endogenous NPY and receptor levels (NPY-Y1R and NPY-Y4R) that were depleted under high pressure conditions.
Molecular analysis revealed NPY works through MAPK and PI3K/Akt signaling pathways to achieve its protective effects.
Palanivel, Viswanthram; Gupta, Vivek; Chitranshi, Nitin; Tietz, Ole; Vander Wall, Roshana; Blades, Reuben; Maha Thananthirige, Kanishka Pushpitha; Salkar, Akanksha; Shen, Chao; Mirzaei, Mehdi; Gupta, Veer; Graham, Stuart L; Basavarajappa, Devaraj · Animal Study
RPEP-09022 · 2024The researchers created chimeric protein biomodulators using enzyme-triggered, cell-penetrating peptides to deliver GADD34-derived motifs into tumor cells. These motifs inhibit protein phosphatase 1 (PP1), which enhances calreticulin exposure on tumor surfaces — an "eat me" signal for immune cells.
The platform was modular, allowing combination with either:
- Cytotoxic BLF1 to provide additional "eat me" signaling through phosphatidylserine exposure
- Immunomodulatory designed ankyrin repeat proteins to block PD-L1 ("don't find me" signaling)
These bifunctional biomodulators induced macrophage phagocytosis, dendritic cell maturation, and CD8+ T cell activation, resulting in substantial tumor growth inhibition.
Pang, Guibin; Chen, Piao; Cao, Xuewei; Yu, Huan; Zhang, Leshuai W; Zhao, Jian; Wang, Fu-Jun ·
RPEP-09026 · 2024After 6 months of oral semaglutide (14 mg/day) in 61 T2D patients: HbA1c decreased by 1.24% (SD 1.33, p significant), fasting plasma glucose decreased significantly, body composition and anthropometric parameters improved significantly, blood pressure decreased, cardiovascular risk factors improved, Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores improved significantly, and SF-36 quality of life scores improved significantly. Average diabetes duration was 4.67 ± 3.93 years.
Pantanetti, Paola; Ronconi, Vanessa; Sguanci, Marco; Palomares, Sara Morales; Mancin, Stefano; Tartaglia, Francesco Carlo; Cangelosi, Giovanni; Petrelli, Fabio ·
RPEP-09028 · 2024Three novel thanatin-like β-hairpin antimicrobial peptides (Rip-2, Rip-3, Rip-4) were discovered in the bean bug Riptortus pedestris through transcriptome mining. Homologs are widely distributed across the insect infraorder Pentatomomorpha.
Rip-2 shared structural similarity with thanatin and targeted the LptA protein, showing higher activity than thanatin against key Gram-negative ESKAPE pathogens. It demonstrated significant efficacy in a lethal mouse septicemia model caused by E. coli at daily doses >5 mg/kg. Rip-3 and Rip-4 had a different mechanism — membrane damage rather than LptA targeting. They showed strong selectivity against Bacillus and Mycobacterium species, did not induce bacterial resistance, and had different antimicrobial spectra.
Panteleev, Pavel V; Teplovodskaya, Julia S; Utkina, Anastasia D; Smolina, Anastasia A; Kruglikov, Roman N; Safronova, Victoria N; Bolosov, Ilia A; Korobova, Olga V; Borzilov, Alexander I; Ovchinnikova, Tatiana V ·
RPEP-09029 · 2024Genome mining revealed rumicidin genes widespread among ruminant mammals. The peptides belong to the proline-rich cathelicidin family and kill bacteria by inhibiting the elongation stage of translation (protein synthesis).
Cryo-EM structural analysis of the E. coli 70S ribosome bound to a rumicidin revealed that the peptide spans the ribosomal A-site cleft and plugs into the nascent peptide exit tunnel, interacting with its constriction point via a conserved Trp23-Phe24 dyad. Bacterial resistance mechanisms involve knockout of the SbmA transporter (needed for peptide uptake) or modification of the MacAB-TolC efflux pump. The peptides demonstrated broad-spectrum antibacterial activity, efficacy in an animal infection model, and no adverse effects on human cells in vitro.
Panteleev, Pavel V; Pichkur, Eugene B; Kruglikov, Roman N; Paleskava, Alena; Shulenina, Olga V; Bolosov, Ilia A; Bogdanov, Ivan V; Safronova, Victoria N; Balandin, Sergey V; Marina, Valeriya I; Kombarova, Tatiana I; Korobova, Olga V; Shamova, Olga V; Myasnikov, Alexander G; Borzilov, Alexander I; Osterman, Ilya A; Sergiev, Petr V; Bogdanov, Alexey A; Dontsova, Olga A; Konevega, Andrey L; Ovchinnikova, Tatiana V ·
RPEP-09030 · 2024Acute intranasal oxytocin at 0.3 IU improved social behavior in Oprm1 knockout mice (autism model) within 5 minutes of administration, with limited effects on non-social behaviors like anxiety or stereotypies.
Chronic oxytocin (8-17 days) maintained its rescuing effects in knockout mice but was deleterious in wild-type mice — an important safety finding. Most importantly, when oxytocin was administered in a social context (paired with social interaction), improvements in social behavior were both greater and longer-lasting compared to oxytocin given without social experience. Under these conditions, expression of oxytocin and vasopressin receptor genes and striatal neuron markers was suppressed. No sex differences in oxytocin effects were detected.
Pantouli, Fani; Pujol, Camille N; Derieux, Cécile; Fonteneau, Mathieu; Pellissier, Lucie P; Marsol, Claire; Karpenko, Julie; Bonnet, Dominique; Hibert, Marcel; Bailey, Alexis; Le Merrer, Julie; Becker, Jerome A J ·
RPEP-09034 · 2024Among 51 migraine patients (43 female, mean age 46 years) treated with anti-CGRP monoclonal antibodies for an average of 15.7 months, 53% had bone density abnormalities (22 with osteopenia, 5 with osteoporosis). However, logistic regression analysis found no association between anti-CGRP treatment duration and bone density abnormalities.
The significant predictors of reduced bone density were menopause (OR 11.641, 95% CI 1.486–91.197, p=0.019) and anti-seizure drug use (OR 12.825, 95% CI 1.162–141.569, p=0.037) — both well-established risk factors for osteoporosis independent of CGRP therapy.
Para, Davide; Camponovo, Chiara; Riccitelli, Gianna Carla; Mallucci, Giulia; Maino, Paolo; Mondini Trissino da Lodi, Camilla; Saudina, Demurtas; Trimboli, Pierpaolo; Gobbi, Claudio; Zecca, Chiara ·
RPEP-09039 · 2024RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells by suppressing NF-κB-dependent expression of adhesion molecules ICAM-1 and VCAM-1. It also blocked M1 macrophage polarization by inhibiting both MAPK and NF-κB signaling pathways.
In ApoE-knockout mice on a high-fat diet, RC-3095 decreased the area of atherosclerotic lesions that were accelerated by P. gingivalis LPS injections, and lowered ICAM-1 and VCAM-1 expression in aortic tissue. These results demonstrate that blocking the gastrin-releasing peptide receptor interrupts multiple inflammatory steps in bacteria-driven atherosclerosis.
Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Yeon; Kim, Hyung Joon; Park, Hae Ryoun; Bae, Soo-Kyung; Bae, Moon-Kyoung ·
RPEP-09044 · 2024LL-37 (human) and CATH-B1 (chicken) cathelicidins significantly reduced PEDV infection of Vero cells at non-toxic concentrations of 5 and 10 µM, effective in both co-incubation (simultaneous) and pre-incubation setups. Transmission electron microscopy revealed that both peptides directly altered virus morphology and caused aggregation of viral particles, reducing infectivity.
Fluorogenic LL-37 was observed entering cells, suggesting a possible immunomodulatory component to its antiviral action. In stark contrast, none of the four porcine cathelicidins (PMAP-36, PMAP-23, PR-39, PG-1) showed any inhibitory effects against PEDV, even at higher concentrations.
Pashaie, Fatemeh; Hoornweg, Tabitha E; Bikker, Floris J; Veenendaal, Tineke; Broere, Femke; Veldhuizen, Edwin J A ·
RPEP-09050 · 2024The review confirms that semaglutide, liraglutide, and tirzepatide demonstrate meaningful weight reduction in real-world settings, consistent with clinical trial results. All three agents show pleiotropic (multi-system) benefits beyond weight loss, including cardiovascular and metabolic improvements. However, the high cost of these medications remains a significant barrier to widespread adoption. Real-world evidence suggests that while efficacy is maintained outside trial settings, affordability and access limitations prevent these drugs from reaching the majority of people who could benefit.
Patoulias, Dimitrios; Koufakis, Theocharis; Ruža, Ieva; El-Tanani, Mohamed; Rizzo, Manfredi ·
RPEP-09056 · 2024Dual CGRP inhibition — combining monoclonal antibodies targeting CGRP or its receptor with oral gepant antagonists — may enhance efficacy by blocking the CGRP pain pathway at multiple points. Combining onabotulinumtoxin A with CGRP-targeted treatments offers potentially synergistic pain relief through complementary mechanisms.
Traditional oral preventives (non-CGRP treatments) remain a practical and affordable combination partner, especially for patients with comorbid conditions. Despite these promising strategies, the review found insufficient evidence to support their routine inclusion in clinical guidelines, and the high cost of biological combination regimens poses feasibility challenges.
Pellesi, Lanfranco; Garcia-Azorin, David; Rubio-Beltrán, Eloisa; Ha, Wook-Seok; Messina, Roberta; Ornello, Raffaele; Petrusic, Igor; Raffaelli, Bianca; Labastida-Ramirez, Alejandro; Ruscheweyh, Ruth; Tana, Claudio; Vuralli, Doga; Waliszewska-Prosół, Marta; Wang, Wei; Wells-Gatnik, William ·
RPEP-09057 · 2024A Phase 2 trial of fremanezumab (anti-CGRP mAb) failed to demonstrate significant efficacy in post-traumatic headache, despite its proven effectiveness in migraine. Evidence for onabotulinumtoxin A in PTH is limited to one small trial with abobotulinumtoxin A in 40 subjects. The review concludes that CGRP inhibition alone may be insufficient for PTH due to the condition's complex, multi-pathway pathophysiology, while ONA's broader mechanism (affecting multiple pain pathways) may offer advantages. ONA also has potential cost-effectiveness and adherence benefits.
Pellesi, Lanfranco; Onan, Dilara; Martelletti, Paolo ·