Bydureon (exenatide XR once-weekly) / AstraZeneca - LARVOL DELTA

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

Estimating the risk of cardiovascular outcomes and all-cause mortality in individuals with type 2 diabetes: Validation of the UKPDS outcomes model using TECOS and EXSCEL data. (PubMed, Diabetes Obes Metab) - "UKPDS-OM2 accurately simulated relative risks between randomized groups in both trials. The proportion of participants with the primary outcome was accurately estimated in both TECOS arms but underestimated by around one-third in both EXSCEL arms."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Ophthalmology • Renal Disease • Type 2 Diabetes Mellitus

Exenatide For Reducing the Reinforcing Effects of Cocaine (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Christopher D. Verrico | N=44 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

Peripheral insulin resistance may predict exenatide treatment response in Parkinson's disease (MDS Congress 2025) - " We performed a phase 3 trial of exenatide once weeklyover 96 weeks in non-diabetic patients with PD (ExPD3). Exenatide did not influence PD progression in the overall ExPD3 trial cohort. In ExPD2, there were a larger number of IR+ patients included, which may explain why exenatide was found to have positive effects overall. Although a non-significant trend towards potential benefit was noted in the small subgroup ofIR+ patients in ExPD3, the hypothesis that IR underpins responsiveness to exenatide would require further trial evaluation of a centrally penetrant GLP1 agonist in PD enriching for IR to formally evaluate this possibility."

CNS Disorders • Movement Disorders • Parkinson's Disease • CRP

LIBERATE-1: Assessment of Safety, Tolerability and Drug Levels of Exenatide Implant (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vivani Medical, Inc | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer's Disease and Parkinson's Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies. (PubMed, CNS Drugs) - "A phase II study testing liraglutide in patients with AD showed first improvements, and two phase II trials testing exendin-4 (exenatide, Bydureon®) or lixisenatide showed improvements in patients with PD...Semaglutide (Rybelsus®; Wegovy®; Ozempic®) is currently in two phase III trials for AD...Newer dual GLP-1/GIP receptor agonists have been developed that can more easily cross the BBB and that show improved protection in animal models of AD and PD. Therefore, GLP-1 and GIP receptor agonists that can cross the BBB show promise as treatments for chronic neurodegenerative disorders."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • IGF1

Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis. (PubMed, Cardiovasc Diabetol) - "These model simulations explain only a modest proportion of the impact of observed EQW-induced changes in conventional CV risk factors on EXSCEL outcomes, apart from hHF and MI. Up to 1-year changes in conventional risk factors did not mediate the observed ACM risk reduction."

Biomarker • Clinical • Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Diabetes • Dyslipidemia • Heart Failure • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy. (PubMed, Ann Neurol) - "Exenatide was associated with positive effects on participant-reported symptoms and clinician-rated MSA severity. In contrast, none of the objective comparisons differed according to randomization. Given the open label trial design, the discrepancy between the primary outcome and the objective measures may be explicable as placebo effects/observer bias. ANN NEUROL 2025."

Journal • CNS Disorders • Movement Disorders • Multiple System Atrophy • NEFL

A Case Series on the Efficacy of the Pharmacological Treatment of Lipedema: The Italian Experience with Exenatide. (PubMed, Clin Pract) - " Five different cases of women with lipedema and insulin resistance, treated with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and once-weekly exenatide, in association or not with lifestyle changes (diet or physical activity) for 3 to 6 months are described. The improvement in symptoms and clinical signs of lipedema, in addition to the reduction in adipose tissue in patients with lipedema and insulin resistance with exenatide, suggests a novel pharmacological approach to the disease, which can be combined with other conservative and surgical treatments to promote weight reduction. These results also highlight the association of this disease with metabolic alterations and the fundamental role of an accurate diagnosis followed by the treatment of comorbidities and excess weight in these patients."

Journal • Aesthetic Medicine • Endocrine Disorders • Genetic Disorders • Inflammation • Obesity • Pain

Effect of the GLP-1 receptor agonist exenatide on pro-inflammatory and metabolic biomarkers in individuals with alcohol use disorder: Post hoc results from a randomized, double-blinded, placebo-controlled clinical trial. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Our findings support the well-established link between AUD and inflammation. However, treatment with the GLP-1 receptor agonist exenatide did not impact pro-inflammatory and metabolic biomarkers."

Biomarker • Clinical • Journal • Retrospective data • Addiction (Opioid and Alcohol) • Dyslipidemia • Metabolic Disorders • Oncology • CCL2 • CRP • CXCL8 • FGF21 • IFNG • IL10 • IL13 • IL2 • IL4 • IL6 • LEP • PPY • TNFA

Utilization of Proteomic Measures for Early Detection of Drug Benefits and Adverse Effects. (PubMed, J Clin Pharmacol) - "Using four clinical trials representing a diverse set of diseases and drug classes (EXSCEL: exenatide/GLP-1 RA, SUGAR-DM-HF: empagliflozin/SGLT2i, PRADA: epirubicin/anthracycline, and AMPLE: abatacept/immunomodulator and adalimumab/TNF inhibitor), we hypothesized that previously validated proteomic measures for cardiometabolic outcomes could enable the detection of beneficial and adverse drug effects in fewer participants over a shorter follow-up period. Changes in SomaSignalTM proteomic tests over time in response to treatment were assessed in the EXSCEL (baseline vs 1 year; once-weekly exenatide (EQW) (n) = 1812 vs control (n) = 1787), SUGAR-DM-HF (baseline vs 12 weeks and 36 weeks; empagliflozin (n) = 45 vs control (n) = 52), AMPLE (baseline vs 85 days and 1 year; abatacept (n) = 210, adalimumab (n) = 222), and PRADA (baseline vs 7-10 days and 3 months, n = 120) trial...In contrast, anthracycline treatment led to significant increases in heart failure mortality risk..."

Adverse events • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Exenatide Once-weekly as a Treatment for Multiple System Atrophy (clinicaltrials.gov) - P2 | N=50 | Completed | Sponsor: University College, London | Recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Multiple System Atrophy

Discontinuation Rates of Once-Weekly GLP-1 Receptor Agonists (GLP-1 RAs) in Patients With Type 2 Diabetes (ISPOR 2025) - "The median time to treatment discontinuation was 327 days for tirzepatide, 240 days for semaglutide, 214 days for dulaglutide, and 153 days for long-acting exenatide... This is among the few studies that assessed discontinuation of once-weekly GLP-1 RAs in patients with T2D. Among once-weekly GLP-1 RA products, tirzepatide had the lowest discontinuation rate."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

BASIC2: Brain Activation and Satiety in Children 2 (clinicaltrials.gov) - P3 | N=63 | Active, not recruiting | Sponsor: Seattle Children's Hospital | Trial completion date: May 2025 ➔ Feb 2026

Trial completion date • Genetic Disorders • Obesity

DUAL GLP-1/GIP RECEPTOR AGONISTS THAT CAN CROSS THE BBB SHOW SUPERIOR NEUROPROTECTIVE EFFECTS (ADPD 2025) - "Methods Bydureon (exenatide) and Adlyxin (lixisenatide) showed disease-modifying protective effects in patients with PD in two phase 2 clinical trials...NLY01, a pegylated form of exenatide that can't cross the BBB did not show any effects in PD patients in a phase 2 trial...Results Currently, two phase 3 trials are ongoing, testing the diabetes drug Ozempic/Wegovy (semaglutide) in AD patients...In animal models of AD or PD, dual agonists were able to protect neurons better than GLP-1 class drugs such as liraglutide, semaglutide or tirzepatide that were designed to treat diabetes and that stay in the blood for longer periods. Conclusions The dual GLP-1/GIP receptor agonist KP405 (DA5-CH) is currently in a phase 1 clinical trial and Results will be shared at the conference."

Alzheimer's Disease • CNS Disorders • Diabetes • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Are Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Central Nervous System (CNS) Penetrant: A Narrative Review. (PubMed, Neurol Ther) - " Preclinical studies indicate that select GLP-1 RAs are CNS penetrant; whether GLP-1 RAs reproducibly engage neural targets hypothesized to subserve dimensions of psychopathology (e.g., general cognitive functions) remains incompletely characterized."

Journal • Review • Alzheimer's Disease • CNS Disorders • Diabetes • Genetic Disorders • Metabolic Disorders • Movement Disorders • Obesity • Parkinson's Disease

Letter to "Risk factors for bone fractures in type 2 diabetes and the impact of once-weekly exenatide: Insights from an EXSCEL post-hoc analysis". (PubMed, Diabetes Res Clin Pract) - No abstract available

Journal • Retrospective data • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Type 2 Diabetes Mellitus

CARDIOVASCULAR OUTCOMES IN NEW USERS OF ONCE-WEEKLY GLP-1 RECEPTOR AGONISTS VS OTHER GLUCOSE-LOWERING THERAPIES AMONG MEDICARE BENEFICIARIES WITH TYPE 2 DIABETES AND ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE - Xi Tan (ACC 2025) - "Individual OW GLP-1 RAs dulaglutide, semaglutide, and exenatide extended-release were also compared against specific NIGLT classes: sodium-glucose cotransporter-2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is). The OW GLP-1RA and other NIGLT matched cohorts had 77,712 and 174,620 patients, respectively... Compared with other NIGLTs, OW GLP-1RAs were associated with a significantly reduced risk of CV outcomes. This further supports guideline-recommended use of OW GLP-1RAs for patients with type 2 diabetes and atherosclerotic CV disease."

Medicare • Reimbursement • US reimbursement • Atherosclerosis • Cardiovascular • Diabetes • Ischemic stroke • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

Risk factors for bone fractures in type 2 diabetes and the impact of once-weekly exenatide: Insights from an EXSCEL post-hoc analysis. (PubMed, Diabetes Res Clin Pract) - "Bone fractures in people with T2D occur more frequently in those with diabetic neuropathy, but less frequently in those taking metformin. No evidence was seen of any impact of EQW treatment on bone fractures."

Journal • Retrospective data • Cardiovascular • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Pain • Type 2 Diabetes Mellitus

Assessment of Exenatide Extended-Release for Maintenance of Diabetic Remission in Cats. (PubMed, J Vet Intern Med) - "Exenatide-ER contributed to the maintenance of glycemic control as reflected by hemoglobin A1c but did not affect remission duration. Management might have contributed to the extended remission duration."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

LIBERATE-1: Assessment of Safety, Tolerability and Drug Levels of Exenatide Implant (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Vivani Medical, Inc | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Managing cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists. (PubMed, Diabetol Metab Syndr) - "Additional studies will be needed in the elucidation of the relations between GLP-1RA-induced miRNAs and clinical-laboratory findings concerning the diverse populations, gender, and presence of other comorbid states in treated patients with T2DM."

Journal • Review • Atherosclerosis • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • MIR126 • MIR130A • MIR139 • MIR15A • MIR181A1 • MIR192 • MIR204 • MIR210 • MIR26A1 • MIR27B • MIR375 • MIR93

Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types. (PubMed, Geroscience) - "Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient's cancer risk profile."

Journal • Bladder Cancer • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Colon Cancer • Colorectal Cancer • Diabetes • Endocrine Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Genetic Disorders • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Adenocarcinoma • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Obesity • Oncology • Ovarian Cancer • Pancreatic Cancer • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Type 2 Diabetes Mellitus • Uterine Cancer

EXCEED: A Pan-European Post-Authorisation Safety Study: Risk of Pancreatic Cancer Among Type 2 Diabetes Patients Who Initiated Exenatide as Compared With Those Who Initiated Other Non-Glucagon-Like Peptide 1 Receptor Agonists Based Glucose Lowering Drugs (clinicaltrials.gov) - P=N/A | N=24000 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Gastrointestinal Cancer • Hepatology • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • Type 2 Diabetes Mellitus

Using QALYs as an Outcome for Assessing Global Prediction Accuracy in Diabetes Simulation Models. (PubMed, Med Decis Making) - "Diabetes simulation models are currently validated by examining their ability to predict the incidence of individual events (e.g., myocardial infarction, stroke, amputation) or composite events (e.g., first major adverse cardiovascular event).We introduce Q2, the proportional reduction in error, as a measure that may be useful for evaluating and comparing the prediction accuracy of econometric or simulation models.We propose using the Q2 or mean squared error for QALYs as global measures of model prediction accuracy when comparing diabetes models' performance for health technology assessment; these can be used to select the most accurate simulation model for economic evaluation and to evaluate the impact of model recalibration in diabetes or other conditions."

Journal • Cardiovascular • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Ophthalmology • Type 2 Diabetes Mellitus