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

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

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

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

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

Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL. (PubMed, Diabetes Care) - "Higher levels of osteoprotegerin and osteopontin are associated with an increased risk of CV events in people with T2D, supporting the hypothesis that pathways involved in bone metabolism play a role in CV disease."

Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus • SPP1 • TNFRSF11B

Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The EXSCEL trial. (PubMed, Eur J Heart Fail) - "The EQW effect on HHF was influenced by LVEF, with a potentially decreased risk in participants with LVEF ≥40% and increased risk in those with LVEF <40%. The risk of HHF was particularly high in participants with LVEF <40% and NYHA class III/IV. LVEF did not modify the effect of EQW on atherosclerotic outcomes."

Journal • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial. (PubMed, Alzheimers Res Ther) - P3 | "EQW treatment was associated with significant change in inflammatory proteins associated with AD."

Journal • Retrospective data • Alzheimer's Disease • Cardiovascular • CNS Disorders • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP

Effect of once-weekly exenatide on, and risk factors for, bone fractures in type 2 diabetes: an EXSCEL clinical trial post-hoc analysis (EASD 2024) - P3 | "Supported By EXSCEL trial was funded by Amylin Pharmaceuticals, a wholly owned subsidiary of AstraZeneca. Among people with T2D, there was no evidence of an impact of treatment with EQW on the risk of bone fractures. This post-hoc analysis of a large randomized clinical trial also suggests that bone fractures more frequently occur among people with diabetic neuropathy, while a reduced risk of fractures was observed among participants using metformin at baseline."

Clinical • Late-breaking abstract • Retrospective data • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Type 2 Diabetes Mellitus

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

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effect of exenatide once weekly on gastric emptying in type 2 diabetes (ANZCTR) - P2 | N=32 | Completed | Sponsor: University of Adelaide | Not yet recruiting ➔ Completed

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

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial. (PubMed, Diabetes Obes Metab) - "eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group."

Adverse events • Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

LIBERATE-1: Assessment of Safety, Tolerability and Drug Levels of Exenatide Implant (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Vivani Medical, Inc | N=16 ➔ 24 | Trial completion date: Jan 2025 ➔ Aug 2025 | Trial primary completion date: Jan 2025 ➔ Aug 2025

Enrollment change • Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Declining eGFR over Time Predicts the Risk of a Composite of Primary or Secondary Major Adverse Cardiovascular Events or Heart Failure Hospitalization, in People with Type 2 Diabetes—EXSCEL Post Hoc analysis (ADA 2024) - "We used a novel statistical approach to investigate the role of eGFR decline in predicting CVD events in people with type 2 diabetes, in both primary and secondary CVD prevention settings. Bayesian joint modelling of eGFR repeated measures and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to examine the association between declining eGFR and the incidence of MACEhF (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, or hospitalization for heart failure), adjusting for age, sex, smoking, hypertension, antihypertensive medication, hyperlipidemia, lipid lowering medication, diabetes duration, atrial fibrillation, HDL-C, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). Declining eGFR over time is a significant predictor of incident MACEhF events in people with type 2 diabetes, both those with and without existing CVD, with a higher hazard ratio for MACEhF in the..."

Adverse events • Clinical • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

DIPIT: Diabetes Islet Preservation Immune Treatment (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: Camillo Ricordi and Jay Skyler | Trial completion date: Dec 2028 ➔ Dec 2029 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Diabetes • Hypoglycemia • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

DIPIT: Diabetes Islet Preservation Immune Treatment (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Camillo Ricordi and Jay Skyler | N=45 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Diabetes • Hypoglycemia • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Hormonal and Physiological Changes Following Short-Term Weight Loss in Adolescents with Obesity and the Role of Glucagon-Like Peptide-1 Receptor Agonists to Counteract Adaptations (ENDO 2024) - P2 | "Following the run-in period, 12 to <18 year olds were randomized 1:1 to 1 year of exenatide extended release (ER; a GLP1-RA) or placebo... Among adolescents with severe obesity achieving short-term weight loss, hormonal and physiological changes favoring weight regain were observed, including reductions in postprandial leptin, amylin, and RMR. Exenatide ER partially counteracted these changes.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Genetic Disorders • Obesity • LEP

Exenatide For Reducing the Reinforcing Effects of Cocaine (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Christopher D. Verrico | Not yet recruiting ➔ Recruiting

Enrollment open

BASIC2: Brain Activation and Satiety in Children 2 (clinicaltrials.gov) - P3 | N=63 | Active, not recruiting | Sponsor: Seattle Children's Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity