glucagon-like peptide-1 oral / Novo Nordisk - LARVOL DELTA

Effects of GLP1 receptor analogues in obesity with neurodevelopmental disorder: case report of a patient with holoprosencephaly. (PubMed, Eur J Clin Nutr) - "GLP1-RAs may be interesting for obesity treatment in the context of neurodevelopmental disorders. They appear to reduce compulsive eating and aggressive behaviour, particularly in relation to exposure to food, and lead to weight loss similar to that seen in people without neurodevelopmental disorders."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Obesity • Psychiatry

DPP-IV inhibition and remyelination: an experimental study using sitagliptin and the cuprizone-induced mouse model of multiple sclerosis (EPNS 2023) - "DPP-IV is expressed in several tissues and some of its substrates, such as glucagon-like peptide-1 (GLP-1) and neuropeptide Y (NPY), hold the potential to exert neuroprotective and neurotrophic properties. Sitagliptin failed to prove efficacy in preventing demyelination and/or promoting remyelination in the CPZ-intoxication mouse model of MS, which might be due to the expressive anti-inflammatory effect demonstrated."

Preclinical • CNS Disorders • Inflammation • Multiple Sclerosis • IL1B • MBP • SOD2

Amelioration of intracerebroventricular streptozotocin-induced cognitive dysfunction by Ocimum sanctum L. through the modulation of inflammation and GLP-1 levels. (PubMed, Metab Brain Dis) - "The histopathological study also showed a significant dose-dependent reduction in amyloid plaque formation and dense granule in PEOS -treated rats as compared to the ICV-STZ induced rats (Negative control). The results show that extract of Ocimum sanctum L. attenuated ICV-STZ-induced learning and memory deficits in rats and has the potential to be employed in the therapy of AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immunology • Inflammation • TNFA

Exendin-4 Preserves Blood-Brain Barrier Integrity via Glucagon-Like Peptide 1 Receptor/Activated Protein Kinase-Dependent Nuclear Factor-Kappa B/Matrix Metalloproteinase-9 Inhibition After Subarachnoid Hemorrhage in Rat. (PubMed, Front Mol Neurosci) - "In this study, we investigated the role of Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, in blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH) in rats. The effects of Ex-4 were reversed by the intervention of GLP-1R siRNA or Dorsomorphin, respectively. In conclusion, Ex-4 could preserve the BBB integrity through GLP-1R/AMPK-dependent NF-κB/MMP-9 inhibition after SAH, which should be further investigated as a potential therapeutic target in SAH."

Journal • Preclinical • Hematological Disorders • Subarachnoid Hemorrhage • MMP9 • RELA

[VIRTUAL] EFFECTIVENESS OF GLUCAGON LIKE PEPTIDE-1 RECEPTOR AGONIST IN NON-ALCOHOLIC FATTY LIVER DISEASE WITH COEXISTING TYPE 2 DIABETES MELLITUS: A SYSTEMATIC REVIEW AND META-ANALYSIS (DDW 2021) - "Interestingly, a reduction in liver fat content was noted in the RTCs for exenatide and dulaglutide, but slightly different methods were used in the trials. A total of 6 RCTs were included in the study with 143 study subjects and 204 controls. The GLP-1 RA significantly reduced the GGT level [mean difference: -14.03 IU/L, 95% CI: (-20.66, -7.41), I2: 60.6%] and BMI [mean difference: -1.26kg, 95% CI: (-2.46, -0.06), I2: 95.4%] compared with control. No significant change of AST [mean difference: -2.32 IU/L, 95% CI: (-8.35, 3.71), I2: 82.3%] and ALT [mean difference: -7.59 IU/L, 95% CI: (-19.12, 3.93), I2: 84.1%] between the GLP-1 RA and the control.The strong relation between NAFLD and T2DM logically leads to the evaluation of antidiabetic agents in the treatment of NAFLD."

Retrospective data • Review • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Obesity • Type 2 Diabetes Mellitus

Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. (PubMed) - Diabetes Obes Metab - P3; "This study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated. ClinicalTrials.gov identifier: NCT01652729."

Journal • Biosimilar • Diabetes

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists. (PubMed) - Diabetes Metab Syndr Obes - "...This review summarizes the key efficacy and safety findings from prospective phase 3 clinical studies of at least 76 weeks' duration for the GLP-1RAs currently approved in the United States and the European Union (albiglutide, dulaglutide, exenatide twice daily [BID], exenatide once weekly [QW], liraglutide, and lixisenatide)...Four-year comparative data demonstrated a longer time to treatment failure for exenatide BID than for sulfonylurea, and 3-year comparative extension data demonstrated greater glycated hemoglobin (HbA1c) reductions and weight loss with exenatide QW than with insulin glargine...Data from DURATION-1 demonstrated that continuous HbA1c reductions and weight loss were observed for the patients continuing on the treatment, with no unexpected adverse events. Taken together, these data support GLP-1RAs as a long-term noninsulin treatment option after the failure of oral therapies."

Journal • Review • Biosimilar • Diabetes

Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice. (PubMed) - PLoS One - "GLP-1 receptor (GLP-1R) was expressed in monocytes/macrophages and linagliptin suppressed GLP-1R expression in MGO-injected mice. These results suggest that oral administration of linagliptin ameliorates MGO-induced peritoneal fibrosis."

Journal • Biosimilar • Fibrosis • Immunology

SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies (clinicaltrials.gov) - P4; N=70; Completed; Sponsor: VU University Medical Center; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Diabetes • Diabetic Nephropathy

ECHO: Energy Balance in Craniopharyngioma-related Hypothalamic Obesity (clinicaltrials.gov) - P3; N=48; Recruiting; Sponsor: Seattle Children's Hospital; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Obesity

EGRABINS1: The Effect of GLP-1 Receptor Agonist on Cerebral Blood Flow Velocity in Non-stroke Volunteers (clinicaltrials.gov) - P2; N=30; Not yet recruiting; Sponsor: Christina Kruuse

New P2 trial • Biosimilar

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. (PubMed) - "Thus, exenatide ER is a useful treatment option in the management of type 2 diabetes. It offers a convenient, once-weekly regimen and can be administered by patients via a pen injection system or syringes and needles."

Journal • Biosimilar • Diabetes

Safety, tolerability, and efficacy of lixisenatide as monotherapy in Japanese patients with type 2 diabetes mellitus: An open-label, multicenter study. (PubMed) - J Diabetes Investig - "Once-daily lixisenatide monotherapy was associated with a safety profile in line with the glucagon-like peptide-1 receptor agonist class and improved glycemic control in Japanese patients with type 2 diabetes mellitus."

Journal • Biosimilar • Diabetes

Abscisic Acid Stimulates Glucagon-Like Peptide-1 Secretion from L-Cells and Its Oral Administration Increases Plasma Glucagon-Like Peptide-1 Levels in Rats. (PubMed) - "Moreover, the development of treatments aimed at stimulating GLP-1 release from L cells has been considered as an alternative approach. Accordingly, our finding that ABA increases GLP-1 release in vitro and in vivo may suggest ABA and/or ABA analogs as potential anti-diabetic treatments."

Journal • Biosimilar • Diabetes

Bioactivity of a modified human Glucagon-like peptide-1. (PubMed) - PLoS One - "Intraperitoneal injections of mGLP-1 into streptozotocin (STZ)-induced type 2 diabetic mice significantly reduced blood sugar levels and stimulated insulin secretion. Oral gavages of mGLP-1 in diabetic mice did not result in significant hypoglycemic activity."

Journal • Biosimilar • Diabetes

Astrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance. (PubMed) - J Neurosci - "Here, we report that GLP-1R agonists activate and internalize within NTS astrocytes, while behavioral data suggest the pharmacological relevance of NTS astrocytic GLP-1R activation for food intake and body weight. These findings support a previously unknown role for CNS astrocytes in energy balance control by GLP-1 signaling."

Journal • Biosimilar • Obesity

Effects of Glucagon Like Peptide-1 on No-reflow (clinicaltrials.gov) - P=N/A; N=190; Recruiting; Sponsor: Chen Wei Ren, MD

New trial • Acute Coronary Syndrome • Biosimilar

Gastric Mucosal Devitalization Reduces Adiposity and Improves Lipid and Glucose Metabolism in Obese Rats. (PubMed) - Gastrointest Endosc - "Devitalization of gastric mucosa, independent of altering gastric volume, was able to reduce obesity related comorbidities. The gastric mucosa may be a potential target to treat obesity and its associated comorbidities."

Journal • Biosimilar • Diabetes • Obesity

Discovery of a novel series of orally bioavailable and CNS penetrant Glucagon-Like Peptide 1 Receptor (GLP-1R) non-competitive antagonists based on a 1,3-disubstituted-7-aryl-5,5-bis(trifluoromethyl)-5,8-dihydropyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione core. (PubMed) - J Med Chem - "A duplexed, functional multi-addition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) non-competitive antagonist. Antagonist 5d not only blocked Exendin-4-stimulated insulin release in islets, but also lowered insulin levels while increasing blood glucose in vivo."

Journal • Biosimilar

Treatment Strategy for Type 2 Diabetes with Obesity: Focus on Glucagon-Like Peptide-1 Receptor Agonists. (PubMed) - Clin Ther - "Overall, the properties of GLP-1RAs make them suitable for combination with oral antidiabetic drugs in the early stages of T2DM and with insulins in the later stages for optimizing comprehensive management of the disease."

Journal • Review • Biosimilar • Diabetes • Immunology • Metabolic Disorders • Obesity • Pancreatitis

IECF-Investigating the Incretin Effect in Cystic Fibrosis (clinicaltrials.gov) - P=N/A; N=50; Completed; Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust; Recruiting ➔ Completed

Trial completion • Biosimilar • Fibrosis • Immunology • Inflammation

Dual actions of a novel bifunctional compound to lower glucose in mice with diet-induced insulin resistance. (PubMed) - "These results suggest that the bifunctional compound could be an effective treatment for individuals with type 2 diabetes and insulin resistance. This strategy could also be employed in other disease conditions characterized by chronic inflammation."

Journal • Biosimilar • Diabetes • Immunology • Inflammation • Obesity

Quantitative Gastrointestinal and Psychological Traits Associated with Obesity and Response to Weight-loss Therapy. (PubMed) - "Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof-of-concept clinical trial, predicted response to pharmacotherapy for obesity. ClinicalTrials.gov no: NCT01834404."

Journal • Biosimilar • Hematological Malignancies • Obesity