Byetta (exenatide) / AstraZeneca - LARVOL DELTA

RYGB Induces Vagal Sensory Neuropathy Characterized by Altered GLP1R Expression and Enhanced Exendin-4 Responsiveness in Male Mice. (PubMed, Am J Physiol Endocrinol Metab) - "Interestingly, this response was notably exaggerated in RYGB animals and those with injured gastric vagus nerves. Collectively, these findings provide both molecular and electrophysiological evidence that RYGB induces vagal neuropathy, characterized by reduced Glp1r expression and heightened sensitivity to GLP1."

Journal • Preclinical • Obesity • Pain • ATF3

Mild-to-moderate depressive symptoms impact on self-reported outcome measures in clinical trials for neurodegenerative diseases. (PubMed, Clin Trials) - P2, P3 | "Mild-to-moderate depressive symptoms, below the threshold for diagnosing a depressive disorder, are associated with negative self-reporting, and such findings should be carefully considered when planning the design and analysis of trials in neurodegenerative diseases."

Journal • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Psychiatry

Prediction of the optimal dose of exenatide in patients with type 2 diabetes mellitus with renal impairment using physiologically based pharmacokinetic modeling. (PubMed, Drug Metab Dispos) - "This study developed and validated physiologically based pharmacokinetic models of exenatide in renal impairment. These new models close the evidence gap for optimal dosing in this population."

Journal • PK/PD data • Diabetes • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

The effects of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on alcohol-related outcomes: a systematic review and meta-analysis. (PubMed, Addict Sci Clin Pract) - "Observational studies suggest a decrease in alcohol-related events, but RCTs have effects on alcohol consumption and craving that remain non-significant. Larger RCTs are needed."

Journal • Retrospective data • Addiction (Opioid and Alcohol)

Formulation and characterization of exenatide-loaded PLGA microspheres prepared by coacervation. (PubMed, Drug Deliv Transl Res) - "Bydureon® is a once-weekly injection of poly(lactide-co-glycolide) (PLGA) microspheres containing exenatide acetate, a synthetic analog of the GLP-1 receptor agonist exendin-4. The framework of conditions and their effects on the formulations was established for loading exenatide in PLGA microspheres with desirable release characteristics. These results are useful for both microencapsulation of generic and new peptides in PLGA microspheres by coacervation."

Journal

Glucagon-like peptide-1 receptor (GLP-1R) agonists prevent tributyltin-induced muscle atrophy/wasting via restoring GLP-1R signaling in vitro and in mice. (PubMed, Ecotoxicol Environ Saf) - "GLP-1R agonists (GLP-1RAs), exendin-4 (Ex-4) and liraglutide (Lira), were tested in C2C12 myotubes (25-500 nM) exposed to TBT (0.25 μM) and in mice orally administered TBT (25 μg/kg/day) with Ex-4 (2.5 μg/kg/day) for 8 weeks. GLP-1R expression in soleus muscle, downregulated by TBT, was restored with Ex-4. These findings demonstrate that GLP-1RAs protect against TBT-induced muscle wasting in vitro, with Ex-4 showing in vivo efficacy through restoration of GLP-1R expression and normalization of apoptosis- and atrophy-related signaling."

Journal • Preclinical • Muscular Atrophy • Myositis

Exendin-4 Reduces Senescence of Inflammation-Induced Periodontal Ligament Stem Cells Through SIRT1/Notch1 Signaling. (PubMed, Stem Cells Int) - "Potential mechanisms underlying the effect were evaluated with regard to senescence-associated molecular pathways, and results demonstrated senescence of PDLSCs to be associated with Sirtuin 1 down-regulation and Notch1 upregulation. Our findings suggest that Ex-4 may mitigate the inflammation-induced senescence of PDLSCs through the SIRT1/Notch1 signaling pathway."

Journal • Dental Disorders • Inflammation • Periodontitis • NOTCH1

GLP-1 receptor agonists reduce body mass index and total daily insulin dose in youth with type 1 diabetes: a retrospective cohort study. (PubMed, J Pediatr Endocrinol Metab) - "This first longitudinal report of GLP-1RA use in youth with T1D and obesity shows clinically meaningful improvements in weight, glycemia, and insulin requirements, supporting the potential role of GLP-1RA as adjunct therapy. Larger prospective studies are needed to guide clinical practice."

Journal • Retrospective data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Pediatrics • Type 1 Diabetes Mellitus

CER-4-T2D: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study (clinicaltrials.gov) - P=N/A | N=781430 | Active, not recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jul 2024 ➔ Jan 2026

HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Design of biomimetic chylomicrons based on 1,3-diolein grafted hyaluronic acid to drive biomacromolecules across the intestinal mucosal barrier. (PubMed, J Control Release) - "Inspired by the natural absorption pathway of dietary triglycerides via chylomicrons, bionic nanoparticles based on 1,3-diolein grafted hyaluronic acid (HA-DOG) were developed to overcome the oral delivery barriers and influence of structural characteristics on the oral fate of exenatide were systematically investigated...In vivo studies revealed that HA-DOG/EAZ NPs achieved a 13.81 % pharmacological bioavailability and exhibited a persistent hypoglycemic effect in type 2 diabetic rats. This study presents a promising strategy for the oral delivery of biomacromolecule drugs, particularly GLP-1 receptor agonists, by mimicking the chylomicron pathway and overcoming key gastrointestinal barriers."

Journal • Diabetes • Type 2 Diabetes Mellitus

Effects of glucagon-like peptide-1 receptor agonists on alcohol consumption: a systematic review and meta-analysis. (PubMed, EClinicalMedicine) - "GLP-1 RAs studied were Semaglutide, liraglutide, dulaglutide, exenatide, and tripeptide. Large, dedicated RCTs are needed to confirm efficacy and define optimal therapeutic strategies. No funding was received for this study."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Systematic review and synthesis without meta-analysis (SWiM) reveals lack of clinical studies and weak preclinical evidence for interaction between glucose regulating drugs and environmental contaminant exposure. (PubMed, Biochem Pharmacol) - "Exendin-4 was investigated twice and glibenclamide once. Small sample sizes, short duration exposures, unrealistic chemical levels, lack of full factorial analysis and absence of testing in suitable T2D models restrict the applicability of the current, limited preclinical evidence for translation to clinical practice. The potential for chemical exposure to impact T2D medication effects on glucose control needs to be addressed with dedicated clinical studies in patients with T2D."

Journal • Preclinical • Retrospective data • Metabolic Disorders

Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis: A Narrative Review. (PubMed, Cureus) - "Its therapeutic potential was long realized, leading to the development of the first GLP-1 receptor agonist, exenatide, followed by liraglutide, dulaglutide, semaglutide, and tirzepatide...Alongside resmetirom, semaglutide is currently approved for the treatment of non-cirrhotic MASH with moderate-to-advanced fibrosis. Safety considerations include gastrointestinal intolerance, hypoglycemia, rare pancreaticobiliary events, and theoretical concerns of thyroid C-cell tumors, though human risk remains minimal. In summary, semaglutide extends the armamentarium of the hepatologist against the most common liver disease worldwide."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Hypoglycemia • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Thyroid Gland Carcinoma • Type 2 Diabetes Mellitus

Amelioration of D-galactose-Induced Hyposalivation in Aging Rats by the GLP-1 Receptor Agonist Exendin-4. (PubMed, Eur J Pharmacol) - "In summary, Exendin-4 exhibits beneficial effects on D-galactose-induced hyposalivation by improving salivary secretion, preserving glandular structure, and decreasing apoptotic cell death.. Thus, Exendin-4 may improve salivary secretion in animal models of aging-related hyposalivation."

Journal • Preclinical • Dental Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Periodontitis • Xerostomia

Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation. (PubMed, Medicine (Baltimore)) - "No significant statistical difference was found between GLP-1 agonists and other obesity and diabetes drugs regarding suicide/suicidal ideation. In a subgroup analysis, suicide was higher in patients on liraglutide compared to semaglutide, with no significant difference between semaglutide and monjaro. Randomized controlled trials that assess the association between GLP-1 agonists and suicidality are highly recommended."

Clinical • Journal • Retrospective data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Psychiatry • Suicidal Ideation

Periodontitis and GLP-1 pathways: a new frontier in oral-systemic health connections -a scoping review. (PubMed, Front Clin Diabetes Healthc) - "GLP-1 RAs, such as liraglutide and exendin-4, demonstrated anti-inflammatory, osteoprotective, and regenerative effects in preclinical models. GLP-1 RAs and DPP-4 inhibitors may offer dual benefits for metabolic control and periodontal health. Further research is needed to define delivery strategies, assess efficacy across patient populations, and explore the therapeutic targeting of DPP-4 activity in both host and microbial contexts."

Journal • Review • Dental Disorders • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • Periodontitis

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Efficacy & safety of sodium-glucose cotransporter-2 inhibitors in polycystic ovary syndrome: A meta-analysis with trial sequential analysis. (PubMed, Indian J Med Res) - "Results Five RCTs with 'low' risk of bias, including 205 patients with PCOS, receiving SGLT2i (empagliflozin, licogliflozin, dapagliflozin, and canagliflozin alone and in combination with metformin) or control (placebo, metformin, or exenatide) were evaluated in the meta-analysis. Interpretation & conclusions The findings of this meta-analysis suggest that SGLT2i improves the hormonal and glycaemic indices in patients with PCOS. It can prove to be a safe alternative in patients not responding to or intolerant of standard pharmacological treatments."

Clinical • Journal • Retrospective data • Acne Vulgaris • Endocrine Disorders • Genetic Disorders • Infertility • Obesity • Polycystic Ovary Syndrome • Sexual Disorders • Women's Health

Positron emission tomography to assess drug occupancy at peripheral and central incretin receptors. (PubMed, EBioMedicine) - "PET imaging in pigs demonstrated in vivo GLP-1R engagement by SAR441255 and tirzepatide, and GIPR engagement by SAR441255 in the pancreas. SAR441255 exhibited dose-dependent GLP-1R occupancy in the pancreas and brain regions linked to appetite regulation."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

GLP-1 receptor agonists and alcohol use disorder: a systematic review. (PubMed, Alcohol Alcohol) - "In this review of three randomized controlled trials (RCTs) (n = 48-151), semaglutide reduced alcohol use, dulaglutide lowered alcohol intake in current drinkers, while exenatide had no significant effect on heavy drinking days. Large RCTs are needed to substantiate the role of GLP-1 RAs in treating alcohol use disorder."

Journal • Review • Addiction (Opioid and Alcohol) • Hepatology • Metabolic Disorders

ON TARGET DM: Comparison of Type 2 Diabetes Pharmacotherapy Regimens (clinicaltrials.gov) - P=N/A | N=241981 | Completed | Sponsor: Kaiser Permanente | Recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Mar 2025

Trial completion • Trial completion date • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Body-wide multi-omic counteraction of aging with GLP-1R agonism. (PubMed, Cell Metab) - "Comparison with mammalian target of rapamycin (mTOR) inhibition, a proven anti-aging strategy, revealed strong multi-omic similarities. Our findings have broad implications for the mechanisms behind GLP-1RAs' pleiotropic benefits, guiding clinical trials, and informing development of anti-aging-based therapeutics."

Journal

Seizure recurrence after GLP-1 receptor agonist initiation in adults with epilepsy. (PubMed, Epilepsia) - "In this large multinational cohort, GLP-1 RA initiation was associated with reduced risks of seizure recurrence, hospitalization, and mortality compared with other glucose-lowering therapies. These hypothesis-generating findings warrant confirmation in prospective studies before translation into clinical practice."

Journal • CNS Disorders • Diabetes • Epilepsy • Metabolic Disorders • Type 2 Diabetes Mellitus

Warfarin and GLP-1 Receptor Agonist Interaction Effects on Time in Therapeutic Range (ASH 2024) - "Semaglutide was the most prescribed GLP1-RA (10, 36%), followed by exenatide (8, 28.5%), dulaglutide (5, 17.5%), liraglutide (4, 14%), and tirzepatide (1, 3.5%)...A subgroup of patients who were well controlled on warfarin had significant changes in their INR in the months following GLP1-RA initiation, however without bleeding events reported. These findings suggest that GLP-1 RAs can be co-administered with warfarin without major impacts on anticoagulation stability, however, this study was limited as it was a retrospective single-center cohort, and further prospective research may be warranted."

Cardiovascular • Diabetes • Hematological Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus • Venous Thromboembolism

Comparison chart: GLP-1 and GIP/GLP-1 receptor agonists for type 2 diabetes. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus