RPEP-13828 · 2025HSD (15 weeks): ↓body weight/VAT mass, ↓adipocyte size, ↑collagen, ↓vascular density, mitochondrial stress, ↑oxidative stress, ↑leptin, ↓adiponectin. Liraglutide (5 weeks): reversed structural damage, ↓oxidative stress, normalized adipokines. C57BL/6 mice.
Touceda, Vanessa; Cacciagiú, Leonardo; Moglie, Ignacio Barbani; Wiszniewski, Morena; Sanchez, Valeria; De Lucca, Romina C; Vidal, Agustina; Finocchietto, Paola; Friedman, Silvia; González, Germán E; Miksztowicz, Verónica ·
RPEP-13829 · 2025Severe refractory dysmenorrhea → resolved with semaglutide. No weight change. Transient appetite loss only. No new medications added. No lifestyle changes. Proposed mechanisms: anti-estrogenic + anti-inflammatory. First case report.
Tran, Mary; Swartz, Nicholas; Elisèe, Sabine D ·
RPEP-13830 · 2025AMPs with anticancer activity: LL-37, HNP, lactoferrin. Mechanisms: apoptosis induction, wound healing, immune modulation. Advantages: abundance, bioavailability, safety, immune compatibility. Applications: standalone or with immunotherapy.
Tran, Tuan Hiep; Le, Thanh Huong; Tran, Thi Thu Phuong ·
RPEP-13831 · 2025Brain-derived GLP-1 (from PPG neurons) is the physiological brain GLP-1R agonist. PPG neurons: brainstem location, multiple populations. Dual function: eating suppression + stress association. Drug target: promising but stress effects need consideration. Different PPG populations may serve different functions.
Trapp, Stefan; Skoug, Cecilia ·
RPEP-13832 · 2025Oral semaglutide in HFpEF + T2DM + obesity: improved health status (symptoms, function). Significant weight loss. First real-world oral semaglutide HFpEF data. Triple-pathology population.
Trenas, Alicia; Pérez-Velasco, Miguel A; Bernal-López, Maria-Rosa; López-Carmona, María-Dolores; Gómez-Doblas, Juan J; Martínez-Esteban, María-Dolores; Bouarich, Oumayma; García-Casares, Natalia; Fernández-García, Diego; de Lucas, María-Dolores García; Gómez-Huelgas, Ricardo; Pérez-Belmonte, Luis M ·
RPEP-13833 · 2025First case-control evaluation of GLP-1RA-associated DLRPN and CFN. Semaglutide already linked to NAION. Both neuropathies associated with weight loss. Possible mechanism: rapid weight loss → nerve ischemia/compression. Expands GLP-1 neurological safety profile.
Triplett, James D; Pinto, Marcus V; Young, Nathan P; Staff, Nathan P; Chinmay, Marathe S; Horowitz, Michael; Aragon Pinto, Catarina; Laughlin, Ruple S; Shouman, Kamal; Berini, Sarah E; Mauermann, Michelle L; Dubey, Divyanshu; Mandrekar, Jay; Dyck, P James B; Klein, Christopher J ·
RPEP-13834 · 2025Dapagliflozin + exenatide: superior β-cell function improvement vs monotherapy. 90-minute OGTT assessment. 90 T2DM patients. Hypothesis confirmed: combination > individual agents for BCF. Insulin sensitivity also improved.
Triplitt, Curtis; Cersosimo, Eugenio; Alatrach, Mariam; Adams, John; Hansis-Diarte, Andrea; Baskoy, Gozde; Gastaldelli, Amalia; Chavez-Velazquez, Alberto; DeFronzo, Ralph A ·
RPEP-13835 · 2025Updated meta-analysis + TSA of GLP-1RA RCTs in PD. Motor and non-motor outcomes assessed. Safety profile evaluated. Mild-to-moderate PD patients. TSA determines evidence sufficiency.
Tsai, Wen-Wen; Lu, Kuan-Hsien; Wu, Jheng-Yan; Chuang, Min-Hsiang; Chen, Jui-Yi; Lai, Chih-Cheng; Hung, Kuo Chuan; Hsieh, Meng-Tsang ·
RPEP-13836 · 2025Differential neuroprotective effects between individual GLP-1RAs and SGLT2i agents. Concentration-dependent responses identified. Four neurological outcomes: delirium, depression, dementia, coma. Agent-specific effects suggest personalized selection possible.
Tseng, Ping-Tao; Zeng, Bing-Yan; Hsu, Chih-Wei; Suen, Mein-Woei; Hung, Chao-Ming; Carvalho, Andre F; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Lin, Pao-Yen; Chen, Jiann-Jy; Su, Kuan-Pin; Wang, Hung-Yu; Zeng, Bing-Syuan; Shiue, Yow-Ling; Liang, Chih-Sung ·
RPEP-13837 · 2025No overall increased gynecologic cancer risk with GLP-1RAs or SGLT2i. 91 RCTs included. NMA: regimen-specific comparisons. First comprehensive gynecologic cancer safety analysis for these drug classes. Addresses growing concern as prescribing increases in women.
Tseng, Ping-Tao; Zeng, Bing-Yan; Hsu, Chih-Wei; Sun, Cheuk-Kwan; Suen, Mein-Woei; Carvalho, Andre F; Stubbs, Brendon; Chen, Yen-Wen; Chen, Tien-Yu; Lei, Wei-Te; Chen, Po-Huang; Chen, Jiann-Jy; Shiue, Yow-Ling; Zeng, Bing-Syuan; Su, Kuan-Pin; Liang, Chih-Sung ·
RPEP-13838 · 2025GLP-1 RAs + SGLT2i: both prevent T2DM in high-risk adults. Individual + combined effects assessed. Updated meta-analysis. Diabetes prevention paradigm.
Tsironikos, Georgios I; Tsolaki, Vasiliki; Zakynthinos, George E; Kyprianidou, Despoina; Rammou, Vasiliki; Antonogiannis, Thomas; Mprotsis, Theodoros; Zakynthinos, Epameinondas; Bargiota, Alexandra ·
RPEP-13839 · 2025Liraglutide: ↓FFA-induced RPE dysfunction. Mechanism: AMPK activation + lipid homeostasis regulation. Protected against: oxidative stress, lipid dysregulation, cellular dysfunction. AMD pathology-relevant model (ARPE-19 cells + FFA). Addresses drusen-related lipid accumulation.
Tsou, Sing-Hua; Luo, Kai-Shin; Huang, Chien-Ning; Kornelius, Edy; Cheng, I-Ting; Hung, Hui-Chih; Hung, Yu-Chien; Lin, Chih-Li; Hsu, Min-Yen ·
RPEP-13840 · 2025Phenotype-guided framework: matches drug mechanism to patient profile. Drug options: GLP-1RA, GIP/GLP-1 (tirzepatide), triple agonists, combinations. Patient factors: metabolic, psychological, complications, age. Across lifespan: pediatric to elderly.
Tuccinardi, Dario; Masi, Davide; Watanabe, Mikiko; Zanghi Buffi, Valeria; De Domenico, Francesco; Berti, Sabrina; Cipriani, Valentina; Manco, Melania; Manfrini, Silvia; Pagotto, Uberto ·
RPEP-13841 · 2025Preclinical: anti-tumor mechanisms (anti-inflammatory, anti-NAFLD, anti-proliferative). Some observational: protective signals. Large VA study: 31% HCC risk increase. Contradictory evidence. Need: longer-term studies. T2DM context.
Tungekar, Bassam; Echevarria Cruz, Evelyn C; Dodrill, Jason; Muneeb, Abdul; Sanderfoot, Rachel; Thaj, Omar; Vaishnav, Jeet; Vahidi, Arash; Hindi, Fadi; Khan, Rayyan; Nagy, Stephanie; Jacobs, Robin J ·
RPEP-13842 · 2025Liraglutide + metformin: superior fracture healing vs monotherapy. Liraglutide: bone-protective effects. Metformin: metabolic benefits. Combination: complementary mechanisms. Partially insulinopenic diabetic rat model.
Turhan, Banu; Sağlam, Sönmez; Yücel, Mücahit Osman; Dalaslan, Raşit Emin; Sungur, Mehmet Ali; Demir, Fatih; Karaduman, Zekeriya Okan; Arıcan, Mehmet ·
RPEP-13843 · 2025Off-label GLP-1 use in bodybuilding: semaglutide, tirzepatide. Folk pharmacology: user-developed dosing/cycling protocols. Risk: unsupervised use, experimentation. Harm reduction: community-developed strategies. Online forums: primary information source.
Turnock, Luke A; Hearne, Evelyn; Germain, Jennifer; Hirst, Mikey; Townshend, Honor D; Lazuras, Lambros ·
RPEP-13844 · 2025First case: gastric pneumatosis on semaglutide. Novel GI complication not previously described. GLP-1 drugs cause delayed gastric emptying (possible mechanism). Can be benign or indicate serious pathology.
Turunen, Andrew M; Coombs, Reilly A; Garg, Sushil Kumar ·
RPEP-13845 · 2025Low BMI → ↑ghrelin → ↑neuronal NPY → NPY receptor activation on cancer cells → ↑brain metastasis. HFD (↓ghrelin) → ↓brain metastasis. NPY receptor blockade → ↓brain metastasis. Clinical: ↑ghrelin/NPY + ↑brain mets in low-BMI lung cancer. "Obesity paradox" explained.
Tyagi, Abhishek; Wu, Shih-Ying; Kim, Jee-Won; Deshpande, Ravindra Pramod; Wu, Kerui; Smith, Eleanor C; Banna, Giuseppe L; Watabe, Kounosuke ·
RPEP-13846 · 2025Weight regain: near-universal but variable rate. HbA1c: worsened. Cardiovascular parameters: deteriorated. Some residual benefit: may persist. Modifiers identified: treatment duration, lifestyle, individual factors. Comprehensive quantification of rebound.
Tzang, Chih-Chen; Wu, Pei-Hsun; Luo, Chiao-An; Chen, Zi-Ting; Lee, Yi-Ting; Huang, Ewen Shengyao; Kang, Yuan-Fu; Lin, Wei-Chen; Tzang, Bor-Show; Hsu, Tsai-Ching ·
RPEP-13847 · 2025Highly sensitive PACAP + CGRP immunoassays developed. Clinical applications: migraine diagnosis, treatment monitoring, therapy selection. No current validated migraine biomarkers exist. Blood-based detection at clinically relevant levels.
Tzara, Ourania; Søderberg, Josefine Nielsen; Bahl, Justyna; Andersson, Emelie; Damlund, Dina Silke Malling; Vestergaard-Klewe, Ib; Harndahl, Mikkel Nors; Jensen, Allan; Asuni, Ayodeji A ·
RPEP-13848 · 2025Semaglutide vs sitagliptin (52 weeks): ↓BMI, WC, HbA1c, LDL-C, non-HDL-C. LDL subfractions: shifted to larger (less atherogenic). HDL subfractions: shifted to more protective. Multivariate: subfraction changes independent of BMI/HbA1c. Sitagliptin: modest HbA1c improvement only.
Tóth, László Imre; Harsányi, Adrienn; Csiha, Sára; Molnár, Ágnes; Lőrincz, Hajnalka; Nagy, Attila Csaba; Paragh, György; Harangi, Mariann; Sztanek, Ferenc ·
RPEP-13849 · 2025Liraglutide modulates multiple GPCR genes in beta-cells. Affected pathways: insulin secretion + beta-cell survival. Systems-level reprogramming beyond GLP-1R alone. GPCRs: key drug targets in diabetes.
Türkol, Melikenur; Bilgen, Türker ·
RPEP-13850 · 2025Enteric neurons produce ADM2 (CGRP-related peptide). ADM2 promotes tissue-protective ILC2 responses. ADM2 limits intestinal inflammation. New neuro-immune circuit identified. Differential: proinflammatory vs tissue-protective regulation.
Uddin, Jazib; Yano, Hiroshi; Parkhurst, Christopher N; Zhang, Wen; Ahmed, Anees; Ribeiro de Godoy, Victoria; Wei, Qianru; Panchakshari, Rohit; Henninot, Antoine; Dasgupta, Surya; Gaudino, Stephen; Emanuel, Elizabeth R; Zeng, Peng; Miranda, Isabella; Hu, Elin; Tsou, Amy M; Artis, David ·
RPEP-13851 · 2025Brain-accessible peptide targets TrkB-T1 (truncated BDNF receptor). Modulates: glia reactivity, neuroinflammation, excitotoxicity. TrkB-T1 interactome-specific targeting. Reduces stroke damage. Novel neuroprotective approach.
Ugalde-Triviño, Lola; Tejeda, Gonzalo S; Esteban-Ortega, Gema M; Díaz-Guerra, Margarita ·
RPEP-13852 · 2025Exenatide: impaired bone healing in rat cortical defect model. Evidence: histopathological (negative), biochemical (negative), in silico (negative). Contrast: liraglutide shows bone-protective effects. 42 male Sprague-Dawley rats.
Ugur, Fatih; Yilmaz, Ibrahim; Guner, Ersin; Albayrak, Mehmet; Taskin, Recep; Sarikas, Nurtac; Bildirici, Mehmet Akif; Dellalbasi, Ayse Basak; Ozcan, Candemir ·
RPEP-13853 · 2025GLP-1 prescriptions surging. Barriers: insurance coverage gaps, high costs, premature non-specialist prescribing. Issues: suboptimal patient selection, inadequate monitoring. Need: improved coverage, cost solutions, specialist involvement.
Ukhanova, Maria; Wozny, Joseph S; Truong, Chau N; Ghosh, Lopita; Krause, Trudy M ·
RPEP-13854 · 2025GLP-1 drug users: significantly ↑retained gastric contents on EGD. Same-day colonoscopy: ↓retained gastric content risk. Colonoscopy bowel prep: effectively empties stomach. Practical solution identified.
Ukwade, Dirin; Hernandez, Luis J; Modi, Zeel; Raza, Hasan S; Siegel, Michael; Nwachukwu, Dexter; Sarraf, Paya; Memon, Abdullah; Booth, Marya; Cooper, Karen; Boulay, Brian R; Mutlu, Ece A ·
RPEP-13855 · 2025Multivariate analysis: different antidiabetic drugs have differential sepsis risk effects. GLP-1RAs + SGLT2i: potential sepsis risk reduction via anti-inflammatory/immune pathways. T2DM: increased sepsis risk from immune dysfunction/inflammation.
Ulambayar, Battamir; Ghanem, Amr Sayed; Nagy, Attila Csaba ·
RPEP-13856 · 2025Three drug classes: distinct immunomodulatory profiles. Metformin: specific cytokine/chemokine modulation. SGLT2i: distinct immune effects. GLP-1RAs: specific immunomodulation. All: contribute to multi-organ protection beyond glucose. DM: metabolic + inflammatory disease.
Ullah, Amin; Shen, Bairong ·
RPEP-13858 · 2025Semaglutide vs placebo in obese HFpEF: consistently improved symptoms, functional capacity, QoL, and weight. Insufficient evidence: mortality and HF hospitalization endpoints. Need: larger event-driven outcome trials.
Umaña Mejia, Carlos Alberto; Sañudo Soto, Claudia Victoria; Robalino, Juan; Hernández, Mayra; Santos Bretón, Myriam Bertha; Garcia-Vasquez, Edwin A; Rocha, Paola; Palacios Brambila, Luis Miguel; Morales, Sergio; Romo, Miguel; Castillo, Jaqueline L; Montelongo Quevedo, Mauricio; Flores Valdés, Jose R ·
RPEP-13860 · 2025Female rats readily self-administered fentanyl (1.85 μg/infusion IV) with marked individual differences in consumption patterns. Rats in estrus showed greater fentanyl intake, greater cue-induced fentanyl seeking, and greater drug-induced reinstatement of fentanyl seeking compared to those in non-estrus phases.
Acute liraglutide treatment (0.3 mg/kg subcutaneous) produced two key effects: it reduced cue-induced fentanyl seeking, and it blocked drug-induced reinstatement of fentanyl seeking. These effects were particularly pronounced when rats were tested during estrus — the very phase associated with greatest vulnerability.
This extends previous findings in male rats to females, supporting the broad applicability of GLP-1 receptor agonists as potential non-opioid treatments for opioid use disorder across both sexes.
Urbanik, Luke A; Booth, Jennifer L; Acharya, Nikhil K; Evans, Brianna B; Grigson, Patricia S ·
RPEP-13866 · 2025In the GRADE trial comparing four diabetes treatments added to metformin, liraglutide (the GLP-1 RA) produced the greatest improvements in beta-cell function. Liraglutide led to the largest increases in insulin secretion rate, glucose sensitivity, and potentiation, with values remaining above baseline even after 5 years. Sitagliptin improved glucose sensitivity with modest other effects. Glimepiride temporarily boosted insulin secretion but minimally affected glucose sensitivity. All treatments showed beta-cell function improvements at year 1 followed by progressive decline, and lower beta-cell function predicted earlier glycemic failure regardless of treatment.
Utzschneider, Kristina M; Tripputi, Mark; Butera, Nicole M; Mari, Andrea; Rosin, Samuel P; Banerji, Mary Ann; Bergenstal, Richard M; Brown, Necole; Carlson, Anders L; DeFronzo, Ralph A; Gramzinski, Michaela R; Harindhanavudhi, Tasma; Kozedub, Alexandra; Sivitz, William I; Steffes, Michael W; Balasubramanyam, Ashok; Rasouli, Neda ·
RPEP-13867 · 2025Liraglutide + empagliflozin: both ↓oxidative stress and ↓inflammation in DCM. Distinct but complementary mechanisms. Supports combination therapy rationale.
Uçar-Ekin, Cemre; Oflazoğllu-Diken, Huda; Baksi, Nazan; Aşir, Fırat; Şahika-Gökdemir, Gül ·
RPEP-13869 · 2025Monthly migraine days were reduced consistently across three one-year treatment cycles: -12.7 days in year 1, -12.4 days in year 2, and -12.9 days in year 3. Baseline migraine days progressively decreased across cycles from 21.1 to 19.0 to 15.9, while residual migraine days decreased from 9.6 to 9.6 to 8.5.
At the end of year 3, the 50% response rate was 38.5% (69/179 patients) in this intention-to-treat analysis. The sustained reduction in monthly migraine days confirms long-term effectiveness, but the remaining high burden of disease in many patients underscores the need for additional treatment approaches and exploration of non-CGRP pathways.
Vaghi, Gloria; Corrado, Michele; Pocora, Maria Magdalena; Bighiani, Federico; Cammarota, Francescantonio; Antoniazzi, Alessandro; Costantino, Luca; Martinelli, Daniele; Allena, Marta; Ghiotto, Natascia; Guaschino, Elena; Bottiroli, Sara; Iannone, Luigi Francesco; De Cesaris, Francesco; Montisano, Danilo Antonio; Grazzi, Licia; Sances, Grazia; Montomoli, Cristina; Tassorelli, Cristina; De Icco, Roberto ·
RPEP-13874 · 2025This systematic review of 22 studies (10 pharmacovigilance, 12 cohort) found mixed results regarding GLP-1 receptor agonists and suicidality. Pharmacovigilance data showed disproportionate reporting of suicidal ideation for semaglutide and liraglutide specifically. However, cohort studies did not consistently show an increased risk of suicidality — and some GLP-1 RAs were actually associated with decreased suicidal ideation and suicide attempts. The authors concluded there is currently inadequate evidence to establish a causal link between GLP-1 RAs and suicidality.
Valentino, Kyle; Teopiz, Kayla M; Cheung, William; Wong, Sabrina; Le, Gia Han; Rosenblat, Joshua D; Mansur, Rodrigo B; McIntyre, Roger S ·
RPEP-13876 · 2025Researchers discovered that GLP-1 receptor agonists (specifically Exendin-4) work on pancreatic beta cells through a previously unknown mechanism involving a protein called Med14. When Exendin-4 activates the GLP-1 receptor, the signaling cascade triggers PKA to phosphorylate Med14 at a specific site (Ser983). This phosphorylation event is essential for turning on beta cell-specific genes linked to diabetes.
Critically, this Med14 pathway explains why sustained GLP-1 agonist exposure produces different effects than brief exposure. Short-term signaling activates immediate response genes, but long-term exposure activates a broader set of beta cell-protective genes through this Med14 mechanism. When researchers mutated the Med14 phosphorylation site, beta cell numbers decreased and the drug's gene-activating effects were suppressed.
Van de Velde, Sam; Yu, Jingting; Evensen, K Garrett; Pakhlevanyan, Edmund; Williams, April E; Shaw, Reuben J; Montminy, Marc · Basic Research
RPEP-13877 · 2025From 693 articles screened, only four studies met inclusion criteria for evaluating blood pressure effects of anti-CGRP monoclonal antibodies in migraine patients. Among these, only one study had low risk of bias, and it reported elevated blood pressure following initiation of anti-CGRP(R)-mAb treatment. The extreme scarcity of quality evidence on this cardiovascular safety concern highlights a major gap in the literature despite widespread use of these drugs.
van der Arend, Britt W H; van Welie, Floor C; Olsen, Michael H; Versijpt, Jan; Van Den Brink, Antoinette Maassen; Terwindt, Gisela M ·
RPEP-13882 · 2025Migraine patients who didn't respond to their first anti-CGRP monoclonal antibody (either erenumab or fremanezumab) benefited from switching to the other class — ligand-targeting to receptor-targeting or vice versa. The 31 patients who switched experienced a reduction of 3.9 monthly migraine days compared to 36 control patients who returned to standard care (95% CI: -6.4 to -1.3, p = 0.004). This demonstrates that failure on one anti-CGRP antibody class doesn't mean the entire CGRP-targeting approach should be abandoned.
van Veelen, Nancy; van der Arend, Britt W H; Hiele, E; van Zwet, E W; Terwindt, Gisela M · Cohort Study
RPEP-13892 · 2025This systematic review of 36 studies (35 preclinical, 1 clinical) found that BPC-157 enhances growth hormone receptor expression and promotes angiogenesis while reducing inflammatory cytokines. In animal models, BPC-157 improved functional, structural, and biomechanical outcomes across muscle, tendon, ligament, and bone injuries.
The sole clinical study was a retrospective review of 12 patients with chronic knee pain who received intraarticular BPC-157 injections — 7 of 12 reported pain relief lasting more than 6 months. BPC-157 has a half-life under 30 minutes, is metabolized in the liver, and cleared by the kidneys. No adverse effects were found in preclinical safety studies, but no clinical safety data exist.
Vasireddi, Nikhil; Hahamyan, Henrik; Salata, Michael J; Karns, Michael; Calcei, Jacob G; Voos, James E; Apostolakos, John M · Systematic Review
RPEP-13893 · 2025Exenatide, a GLP-1 receptor agonist peptide, improved adiponectin signaling in rats with polycystic ovary syndrome (PCOS). PCOS rats showed diminished adiponectin levels and elevated adiponectin receptor 1 (Adipo-R1) mRNA. Treatment with exenatide at both 50 mg/kg and 100 mg/kg doses restored adiponectin expression and normalized Adipo-R1 levels, suggesting the peptide may improve PCOS through molecular regulation of the adiponectin system.
Vatankhah, Asma; Jamhiri, Mohabbat; Vatankhah, Sima; Lorian, Keivan; Rezvani, Mohammad Ebrahim; Izadi, Mahin · Animal
RPEP-13899 · 2025The peptides Angiotensin 1-7 (Ang 1-7) and Brain Natriuretic Peptide (BNP) significantly reduced TLR4-mediated injury in renal and vascular smooth muscle cells stimulated by Angiotensin II. Specifically, these peptides reversed the upregulation of inflammation, fibrosis, and hypertrophy markers caused by Ang II, and prevented the harmful phenotypic switch in vascular smooth muscle cells.
The protective effects operated through inhibition of the TLR4 signaling pathway, a key driver of end-organ damage in hypertension.
Venkadakrishnan, Jegadheeswari; Vemana, Anusha; Ghatage, Trupti; Vesmaker, Kushal; Bhat, Audesh; Jadhav, Kirtikumar B; Dhar, Arti ·
RPEP-13903 · 2025In a rotenone-induced rat model of Parkinson's disease, the plant compound plumbagin (20 mg/kg orally) improved motor deficits and increased both dopamine and GLP-1 peptide levels in the brain. Plumbagin also reduced RAGE (receptor for advanced glycation end products) levels, a marker of neuroinflammation.
The findings suggest that plumbagin's neuroprotective effects may be mediated through activation of the GLP-1 signaling pathway, which has independently been shown to have neuroprotective properties in Parkinson's disease models.
Verma, Aanchal; Goyal, Ahsas · Animal
RPEP-13904 · 2025Four small peptides show therapeutic potential for Alzheimer's disease by targeting amyloid toxicity, tau hyperphosphorylation, and synaptic degeneration at the molecular level. However, their clinical use is limited by poor bioavailability and rapid enzymatic breakdown.
Advanced delivery strategies — including intranasal administration, nanoparticle encapsulation, and chemical modifications — can overcome these barriers and significantly enhance the peptides' ability to reach brain targets and restore cognitive function.
Verma, Poonam; Khatun, Rubina; Jew, Kiran Anjum; Prusty, Shakti Ketan; Knafo, Shira · Narrative Review
RPEP-13907 · 2025In 106 patients (52.8% chronic migraine, 87.7% female, mean age 50.6):
- Monthly migraine days decreased by 6.9 (SD 9.7, p<0.001) from baseline to 12 weeks
- 50% response rate: 48.1% of patients achieved ≥50% reduction in migraine days
- Significant reductions in acute medication use, disability scores (MIDAS), allodynia (ASC-12), and treatment optimization (mTOQ-6)
- Quality of life improved (MSQ role-function restriction)
- Only 6.6% dropout (4 for lack of efficacy, 3 for adverse events)
- Prior failure on anti-CGRP monoclonal antibodies was NOT a negative prognostic factor in the regression analysis
Vernieri, Fabrizio; Iannone, Luigi Francesco; Lo Castro, Flavia; Sebastianelli, Gabriele; De Santis, Federico; Corrado, Michele; Marcosano, Marilena; Ornello, Raffaele; Grazzi, Licia; Montisano, Danilo Antonio; De Cesaris, Francesco; Munafò, Antonio; Fofi, Luisa; Doretti, Alberto; Vaghi, Gloria; Pistoia, Francesca; Ferrandi, Delfina; Battistini, Stefania; Sacco, Simona; Guerzoni, Simona; Altamura, Claudia ·
RPEP-13916 · 2025A 17-year-old male with juvenile Huntington disease and severe obesity (BMI 44 kg/m²) was treated with semaglutide starting at 0.25 mg weekly, titrated to 1 mg. After 3 months on semaglutide, his BMI decreased by 7% to 40 kg/m². He then underwent laparoscopic sleeve gastrectomy at age 18. Six months postoperatively, his BMI dropped to 33 kg/m², liver enzymes improved, obstructive sleep apnea resolved, and he reported improved physical activity and quality of life.
Vidmar, Alaina P; Martin, Matthew J; Abel, Stuart; Kim, Aimee G; Muñoz, Cynthia E; Weitzner, Madeleine; Derrington, Sabrina F; Samakar, Kamran ·
RPEP-13921 · 2025In this definitive phase 3 trial, the GLP-1 receptor agonist exenatide did NOT slow Parkinson's disease progression compared to placebo. After 96 weeks, Parkinson's motor symptoms worsened by 5.7 points in the exenatide group versus 4.5 points in the placebo group on the MDS-UPDRS III scale — no meaningful difference (p=0.47).
The drug was safe and well-tolerated, with serious adverse events actually slightly lower in the exenatide group (9% vs 11%). But the primary hypothesis — that exenatide could be a disease-modifying treatment for Parkinson's — was not supported by the data.
Vijiaratnam, Nirosen; Girges, Christine; Auld, Grace; McComish, Rachel; King, Alexa; Skene, Simon S; Hibbert, Steve; Wong, Alan; Melander, Sabina; Gibson, Rachel; Matthews, Helen; Dickson, John; Carroll, Camille; Patrick, Abigail; Inches, Jemma; Silverdale, Monty; Blackledge, Bethan; Whiston, Jessica; Hu, Michele; Welch, Jessica; Duncan, Gordon; Power, Katie; Gallen, Sarah; Kerr, Jacqueline; Chaudhuri, K Ray; Batzu, Lucia; Rota, Silvia; Jabbari, Edwin; Morris, Huw; Limousin, Patricia; Greig, Nigel; Li, Yazhou; Libri, Vincenzo; Gandhi, Sonia; Athauda, Dilan; Chowdhury, Kashfia; Foltynie, Tom · Randomized Controlled Trial
RPEP-13922 · 2025In 50 MSA patients, exenatide-treated participants showed less worsening on the clinician/patient-rated UMSARS scale (6.1 vs 13.3 points at 48 weeks, adjusted difference -7.4 points, p=0.0003) — a seemingly impressive result. However, none of the objective secondary measures showed significant differences: ambulation loss, falls, speech, swallowing, timed walking, cognition, neurofilament light chain, CSF alpha-synuclein oligomers, gait sensors, or brain imaging were all similar between groups.
The authors candidly conclude that the discrepancy between the positive subjective primary outcome and the negative objective measures is likely due to placebo effects and observer bias inherent to the open-label design.
Vijiaratnam, Nirosen; Girges, Christine; Wiegand, Martin; Ismail, Claudia; Lameirinhas, Alexandra; Yarnall, Alison; Kirk, Cameron; Del-Din, Silvia; Rochester, Lynn; Kobylecki, Christopher; Ambler, Gareth; Skene, Simon; Houlden, Henry; Chelban, Viorica; Heslegrave, Amanda; Phillips, Wendy; Whone, Alan; Quinn, Niall; Lambert, Christian; Dore, Charlotte; Morris, Huw R; Horrocks, Mathew H; Lee, Ji Eun; O'Shaughnessy, Judi; Li, Yazhou; Greig, Nigel H; Gandhi, Sonia; Libri, Vincenzo; Athauda, Dilan; Foltynie, Tom ·
RPEP-13923 · 2025Using dual mass spectrometry approaches on electrically extracted Apis cerana indica venom:
**High-molecular-weight compounds:**
- 114 compounds identified across 69 protein families
- Major Royal Jelly Proteins (MRJPs) were the most dominant family: MRJPs 1-7 all detected
- MRJP 1 had the highest peptide match scores and spectrum matches among all venom proteins
**Low-molecular-weight compounds:**
- 159 total compounds detected
- 136 metabolite compounds, dominated by fatty acid derivatives (42.05%)
- 23 volatile compounds, dominated by alcohols (58.16%)
The study represents a substantial expansion of the known composition of A. cerana indica venom.
Vikaash, Muthuraja; Kanagarajan, Rasappan; Manikandan, Eswaramoorthy; Dharani, Venkatraman ·
RPEP-13929 · 2025Across ONWARDS 1-5 (3,765 participants), 21.3% were using a GLP-1 RA and 36.9% were using an SGLT2i at baseline. There were no statistically significant treatment interactions by GLP-1 RA or SGLT2i subgroups for HbA1c change, body weight change (with one minor exception), weekly insulin dose, or achievement of HbA1c <7% without clinically significant hypoglycemia.
Rates of clinically significant or severe hypoglycemia were less than 1 episode per patient-year across all trials (except ONWARDS 4, a basal-bolus trial), regardless of GLP-1 RA/SGLT2i use. The efficacy and safety profile of icodec versus daily insulin was consistent across all subgroups.
Vilsbøll, Tina; Fu, Ariel; Kellerer, Monika; Kumar, Bharath; Søgaard, Stinne Byrholdt; Goldenberg, Ronald ·
RPEP-13930 · 2025Mediation analysis across SURPASS-1, -2, and -5 trials (n=2,831) showed that tirzepatide's HbA1c reduction relative to placebo ranged from -14.6 to -20.0 mmol/mol, with weight loss mediating 12-27% of this effect in monotherapy and 25-45% with background insulin therapy. Relative to semaglutide 1 mg, the HbA1c difference ranged from -1.9 to -5.1 mmol/mol, with 54-71% mediated through weight loss. This demonstrates that tirzepatide's glycemic superiority involves substantial weight-loss-independent mechanisms, particularly when compared to placebo.
Vilsbøll, Tina; Malecki, Maciej T; Sharma, Palash; Thieu, Vivian T; Chivukula, Krishna Karthik; Kiljanski, Jacek ·