Byetta (exenatide) / AstraZeneca - LARVOL DELTA

Single-dose CR059, a circular RNA-encoded GLP-1 analogue, enables sustained exposure and prolonged body weight reduction in non-human primates (EASD 2026) - "Materials and Male healthy rhesus monkeys (n=2/group, baseline body weight ~7-8 kg) received single subcutaneous doses of CR059 (180 or 540 µg/kg) or reference exenatide (Byetta, 0.6 µg/kg, twice daily for 5 weeks). Single-dose CR059 demonstrates rapid and robust body weight-lowering activity in rhesus monkeys, with clear dose- dependent effects and sustained plasma GLP-1RA exposure. Its long-acting profile allows for monthly dosing, potentially reducing gastrointestinal side effects such as nausea and vomiting, and supporting continuous therapy as an alternative or follow-up to existing GLP-1RAs. Together, the PK, PD, and ddPCR data highlight CR059's potential as a durable circRNA-based GLP-1 therapy for weight management and other metabolic diseases."

Circular RNA • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Association between GLP-1 receptor agonist use and incident malignancy in Japanese patients with type 2 diabetes: a Japanese claims database study (EASD 2026) - "Adults with T2D who initiated a GLP-1RA (dulaglutide, liraglutide, exenatide, or lixisenatide) were compared with patients without GLP-1RA exposure receiving other antidiabetic drugs. In this propensity score-matched analysis of Japanese adults with T2D, GLP-1RA use was associated with a significant increase in overall cancer incidence, with signals in several cancer sites. Exploratory analyses suggested possible heterogeneity across individual GLP-1RAs. Further studies are needed to clarify underlying mechanisms and differences across agents or patient subgroups."

Claims database • Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Glucagon-like peptides 1 regulates glucose homeostasis by increasing endoplasmic reticulum-mitochondria contact sites in the liver (EASD 2026) - "Materials and We analyzed the effects of GLP-1 receptor (GLP-1R) agonists (Endogenous GLP-1, Exendin-4 [Ex4 - 100 nM] and liraglutide [0.2 mg/kg]) in presence or not of its antagonist (Exendin-9 [Ex9- 100 nM]) on MAM integrity, after 1h of incubation, and insulin action after 3h : (i) in vitro in Huh7 cells under basal conditions or after a challenge with palmitate (200 µM; 18h). These findings uncover MAMs as a previously unrecognized mechanism underlying GLP-1 action, with potential implications for improving hepatic insulin sensitivity."

Metabolic Disorders • VDAC1

Early beta cell dysfunction is linked to reduced GLP-1 sensitivity of islets in humans (EASD 2026) - P | "After recovery, islets were stimulated with 3.3 mM low glucose (LG) and 16.7 mM high glucose (HG), with and without 5 mM Exendin 4 (Ex4), a GLP- 1Ra... Our data highlight a possible link between impaired first-phase insulin secretion and reduced incretin sensitivity at the islet level, even at an early stage of glucose dysregulation. Translationally, reduced RS in vivo could help identify individuals who may benefit from therapies aimed at restoring incretin sensitivity. Further studies integrating proteomic and transcriptomic analyses are needed to uncover the cellular mechanisms underlying reduced islet incretin sensitivity."

Metabolic Disorders

Beta cell mass and function, pancreatic volume and -fat content differences between short- and long-duration type 1 diabetes: a detailed PET-CT imaging study (EASD 2026) - P=N/A, P2 | "Materials and Data of 16 individuals with short-duration (<7 years) and 10 with long-duration type 1 diabetes (≥7 years), who underwent [ 68 Ga]Ga-NODAGA-exendin-4 Positron Emission Tomography/Computed Tomography (PET/CT) scan and mixed-meal tolerance test were used to assess beta cell mass and function, respectively... These results provide promising insights in the decline of beta cell mass during the course of type 1 diabetes and shows the potential of imaging markers together with function tests to monitor disease progression. This may offer valuable information for timing to restore beta cell function or to slow down beta cell destruction."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Associations between [18F]FB(ePEG12)12-exendin-4 PET-derived beta cell mass and clinical parameters in type 1 diabetes (EASD 2026) - "In people with T1D, BCM derived from 18 F-exendin-4 PET/CT was associated with clinical indices, including fasting CPI, HbA1c, insulin requirement and diabetes duration. These findings suggest that 18 F-exendin-4 PET/CT may be useful as a quantitative approach to link BCM to clinical status in T1D. This method may have potential utility for patient stratification and treatment-response monitoring in future studies."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

A role for peptidyl-glycine alpha-amidating monooxygenase (PAM) in GLP-1 biology and GLP-1 receptor agonist response revealed by type 2 diabetes genetic risk (EASD 2026) - P=N/A, P3, P4 | "Inducible whole-body Pam knockout mice were generated; gastric emptying was assessed by paracetamol absorption assay with and without exendin-4. Glycemic response to GLP-1RAs was evaluated in a meta-analysis of 1,119 participants across three cohorts (IMI-DIRECT, GoDARTS, PRIBA), with comparative assessment of sulphonylurea, metformin, and DPP-4 inhibitor response... Hypomorphic PAM T2D-risk alleles reduce amidating enzyme activity, elevate circulating GLP-1 levels, and impair GLP-1 post-receptor signaling, culminating in a selective and clinically meaningful reduction in GLP-1RA efficacy. These findings establish PAM genotype as a novel pharmacogenomic determinant of GLP-1RA response, supporting its incorporation into precision medicine frameworks to optimize drug selection in T2D management."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Metabolic stress disrupts the PDX1-CHD5 chromatin axis and impairs pancreatic beta cell function (EASD 2026) - "Incretin signaling through GLP-1 receptor agonists such as Exendin-4 supports beta cell survival and function, though the link between NuRD members and GLP-1R agonists remain unclear... Our findings identify CHD5 as a metabolically responsive chromatin regulator that cooperates with PDX1 to support beta cell transcriptional integrity. Disruption of the PDX1-CHD5 axis occurs in obesity in rodents and in human T2D. Coordinated activity between CHD4 and CHD5 appears necessary for maintaining beta cell function and identity."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CHD4 • PDX1

Pancreatic delta cells are resistant to auto- and paracrine inhibition in human type 2 diabetes (EASD 2026) - "Cells were challenged with glucose and modulators of cAMP signalling (glucagon, exendin-4, forskolin), GABA, insulin, somatostatin and adrenaline... Human delta-cells show strong autocrine and adrenergic inhibition in ND donors but become resistant to these inhibitory signals in T2D, associated with reduced SSTR2 surface expression. This disinhibition may promote delta-cell hyperactivity and excessive somatostatin output, contributing to impaired intra-islet hormone coordination in diabetes."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • KEAP1 • SSTR2

Long-Term Retrospective Evaluation of Radiochemical Yield Reproducibility of ⁶⁸Ga-Radiopharmaceuticals Using an SiO₂-Based ⁶⁸Ge/⁶⁸Ga Generator. (PubMed, Nucl Med Mol Imaging) - "Fluctuations in radiochemical yields were observed as the generator aged in the radiosynthesis of [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-Exendin-4 whereas it was unaffected with [68Ga]Ga-HBEDCC-PSMA-11. The radiochemical yields are influenced as the generator ages, however, the extent of influence will depend on the chelating agent and buffer systems used for making the targeting molecule."

Journal • Retrospective data

GLP-1 Agonist Use and Outcomes in Connective Tissue Disease-Associated Interstitial Lung Disease (ACR Convergence 2026) - "Patients were categorized as GLP-1 RA users (including semaglutide, dulaglutide, liraglutide, albiglutide, exenatide, lixisenatide) or non-users, and outcomes were evaluated over a 5-year follow-up. In this large propensity score-matched cohort of patients with CTD-ILD, GLP-1 RA use was associated with a significantly reduced risk of mortality. These findings suggest a potential protective role of GLP-1-based therapies and support prospective studies to further define their role in risk modification and disease outcomes in CTD-ILD."

Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Genetic Disorders • Heart Failure • Inflammatory Arthritis • Interstitial Lung Disease • Metabolic Disorders • Myocardial Infarction • Myositis • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Sjogren's Syndrome • Systemic Sclerosis • Type 2 Diabetes Mellitus

Association of GLP-1 Receptor Agonists with Pulmonary Hypertension, Interstitial Lung Diseases, and Major Cardiovascular Events in Systemic Sclerosis (ACR Convergence 2026) - "Exposure included dulaglutide, semaglutide, liraglutide, exenatide and tirzepatide. GLP-1 RA use in patients with systemic sclerosis was associated with a substantial reduction in mortality and significantly lower oxygen supplementation requirements without a corresponding reduction in pulmonary hypertension, interstitial lung disease, or cardiovascular events. These findings suggest a potential survival benefit independent of cardiopulmonary outcomes, and warrant further prospective studies to elucidate underlying mechanisms and confirm causality. Table 1: Outcomes in systemic sclerosis (SSc) patients on GLP-1 RA versus not on GLP-1 RA within 5 years of diagnosis."

Acute Kidney Injury • Cardiovascular • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

GLP-1 Receptor Agonist Therapy Gap and Metabolic Syndrome Burden in U.S. Adults With Psoriatic Arthritis: A Nationally Representative Cross-Sectional Analysis (ACR Convergence 2026) - "A 2026 trial of tirzepatide plus ixekizumab demonstrated superior PsA remission versus ixekizumab alone, supporting GLP-1 receptor agonists as a potential adjunct in PsA...Despite confirmed GLP-1 detectability in NHANES 2017-2023 (80 GLP-1 users identified across semaglutide, liraglutide, dulaglutide, exenatide, and tirzepatide), no PsA patient was receiving a GLP-1 agent. More than half of U.S. adults with PsA have metabolic syndrome driven by obesity – directly targetable by GLP-1 receptor agonists. Nearly 3 in 4 PsA patients meet FDA criteria for GLP-1 therapy, yet none are receiving one, while fewer than 1 in 10 are on statins. These findings provide population-level evidence supporting integrated inflammatory-metabolic treatment strategies in PsA and identify a substantial cardiovascular prevention gap in current clinical practice."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Immunology • Inflammatory Arthritis • Metabolic Disorders • Obesity • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies

GLP-1 Receptor Agonists (RAs) Use and Kidney and Cardiovascular Outcomes in Adults with CKD and Obesity Without Diabetes: A Retrospective Real-World Study (KIDNEY WEEK 2026) - "The exposed cohort included patients treated with GLP-1 RAs, including semaglutide, dulaglutide, liraglutide, tirzepatide, lixisenatide, or exenatide...Conclusion These findings suggest potential kidney-protective and cardiorenal benefits of GLP-1 RAs beyond diabetes. Further studies incorporating CKD stage, eGFR, albuminuria, and randomized trials are warranted."

Real-world • Real-world evidence • Retrospective data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Dyslipidemia • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Harmine Plus Exendin-4 Enhances Remission of Recent-Onset Type 1 Diabetes Following Anti-CD3 Therapy. (PubMed, bioRxiv) - "Together, these findings demonstrate that H+E promotes β-cell recovery and resilience while reducing β-cell immunogenicity, enabling remission of recent-onset T1D when combined with anti-CD3 therapy. SNHG6 emerges as a novel regulator of β-cell protection during inflammation."

Journal • Diabetes • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus

Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues. (PubMed, BMJ Open) - "This study complements existing evidence from clinical trials and current clinical practice."

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

GLP-1 receptor agonists in psoriasis management. (PubMed, Clin Dermatol) - "Observational studies of liraglutide, semaglutide, exenatide, dulaglutide, and tirzepatide generally demonstrated improvements in psoriasis severity, body weight, metabolic parameters, inflammatory biomarkers, and quality of life, although most were limited by small sample sizes and uncontrolled designs...Most notably, the phase 3b TOGETHER trial demonstrated greater skin clearance and weight reduction with ixekizumab plus tirzepatide compared with ixekizumab alone in patients with moderate-to-severe psoriasis and overweight or obesity. Complementary findings from the TOGETHER-PsA trial showed improvement in psoriatic arthritis disease activity as early as week 4, before clinically meaningful weight loss, supporting potential weight-independent anti-inflammatory effects of these agents. Future studies should include patients without obesity or diabetes to clarify the relative contributions of weight loss and direct anti-inflammatory effects to clinical response and..."

Journal • Cardiovascular • Dermatology • Diabetes • Genetic Disorders • Immunology • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Musculoskeletal Diseases • Obesity • Psoriasis • Psoriatic Arthritis • Psychiatry • Rheumatology • Seronegative Spondyloarthropathies • Type 2 Diabetes Mellitus • RAS

How large must a Parkinson’s disease trial be to detect pharmacogenomic interactions? Power benchmarks derived from the Exenatide PD3 clinical trial (MDS Congress 2026) - "Post hoc PGx analyses in clinical trials are constrained by insufficient power to detect meaningful G×T interactions. Larger clinical trials, genotype-stratified designs and consortium-level meta-analysis offer alternatives to overcome this limitation."

Biomarker • Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • NEFL • Plasma NfL

Efficacy and Safety of GLP-1 Receptor Agonists in Parkinson’s Disease: A Meta-Analysis Integrating the 96-Week Phase 3 Exenatide Trial Results (MDS Congress 2026) - " Five randomized controlled trials involving 708 patients evaluating exenatide, lixisenatide, and NLY01 were included. This updated meta-analysis incorporating phase 3 evidence does not demonstrate a significant clinical benefit of GLP-1RAs on motor or non-motor outcomes in patients with Parkinson’s disease. Despite promising preclinical neuroprotective mechanisms, current clinical evidence does not support routine use of these agents for disease modification in PD. Future research should focus on identifying responsive patient subgroups and agents with improved central nervous system penetration."

P3 data • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease

Astrocyte Derived Extracellular Vesicle miR 210 Expression in Exenatide Treated Patients with Parkinson’s Disease (MDS Congress 2026) - "This workflow provides a valuable platform for future translational studies evaluating ADEV‑associated miRNAs, including hypoxia‑responsive miR‑210, as mechanistically informative biomarkers in Parkinson’s disease."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • CD9 • HIF1A • MIR210

The GLP-1 Agonist Paradox in Parkinson’s Disease: A Comparative Analysis of Lixisenatide and Exenatide Phase III Trial Outcomes and Neuroprotective Mechanisms (MDS Congress 2026) - "The GLP-1 paradox stems from pharmacokinetic variations and assessment timing. Optimal BBB penetration is essential to block A1 astrocyte neurotoxicity. Future trials must prioritize central influx and standardize OFF-state assessments to demonstrate disease modification."

P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

GHRH and GLP-1 receptor agonism promote human β-cell survival and improve glucose homeostasis in diabetic mice. (PubMed, Endocrinology) - "Here, we investigated the effects of the GHRH-R agonist MR-409, alone or in combination with the GLP-1R agonist exendin-4 (Ex-4), on β cell survival and glucose homeostasis...Notably, MR-409 treatment was associated with greater improvements in glucose tolerance and insulin levels. These findings support further investigation of GHRH receptor agonism as a strategy to preserve β-cell survival under diabetogenic stress."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CASP3 • CASP7 • IRS2

Recent Studies on the Effectiveness and Safety of Anti-Obesity Medications: A Scoping Review. (PubMed, Diabetes Metab Syndr Obes) - "The review encompassed glucagon-like peptide-1 receptor agonists (GLP-1 RA), including semaglutide, liraglutide, exenatide, and orforglipron; multi-receptor incretin agonists, including tirzepatide, retatrutide, and survodutide; amylin-based combination therapy (cagrilintide plus semaglutide); established non-incretin AOMs (orlistat, phentermine, phentermine/topiramate, and naltrexone/bupropion); microbiome-targeted therapies; and nutraceutical-based interventions. Overall, incretin-based therapies currently provide the greatest weight-loss benefit, although evidence for several emerging pharmacotherapies, microbiome-targeted therapies, and nutraceutical-based interventions remains limited. Further well-designed comparative trials, mechanistic studies, and long-term real-world investigations are needed to better establish the durability, safety, and clinical applicability of emerging AOMs."

Journal • Review • Genetic Disorders • Obesity

Beyond Injection-Site Reactions: A Systematic Review of Cutaneous Adverse Events Associated with Incretin-Based Therapies (EADV 2026) - "Generalized hypersensitivity reactions represent a second tier, ranging from rare, high-stakes Type I immediate responses like anaphylaxis (more prevalent in exendin-4–based molecules with lower human homology) to delayed Type IV maculopapular eruptions that generally resolve upon stopping treatment...As clinical use expands, clinicians must recognize these emerging phenotypes, particularly allodynia and dysesthesia, to ensure appropriate diagnosis and avoid unnecessary diagnostic procedures. Further research into GLP-1 receptor expression in the peripheral nervous system and skin is required to fully elucidate the pathways of neurogenic skin pain"

Adverse events • Review • Bullous Pemphigoid • Dermatopathology • Immunology • Inflammation • Vasculitis

Modulation of Endoplasmic Reticulum Stress via CEBPB: A Potential Molecular Link to Therapeutic Action in Substance Use Disorders. (PubMed, CNS Neurosci Ther) - "These findings highlight ER stress modulation as a convergent pathway with potential therapeutic relevance for substance use disorders."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse • CEBPB • TRIB3