Byetta (exenatide) / AstraZeneca - LARVOL DELTA

Effects of glucagon-like peptide 1 receptor signaling in the dorsolateral septum on ethanol operant self-administration and relapse behaviors. (PubMed, Neuropharmacology) - "On self-administration test days, rats received intra-dLS injections of GLP-1 receptor agonist Exendin 4 (Ex4; 5 ng, 25 ng) or vehicle...Finally, retrograde tracing results showed that dLS receive input from NTS GLP-1-expressing neurons. Together, these findings support the dLS as a key region in mediating the effects of GLP-1 receptor signaling on ethanol self-administration and reacquisition but suggest different contributing mechanisms in reinstatement of ethanol seeking."

Journal • Addiction (Opioid and Alcohol) • NTS

Eustachian Tube Disorders in Patients Prescribed Glucagon-like Peptide-1 (GLP-1) Agonists: A Propensity Score Matching Analysis (AAO-HNSF 2025) - "Analyses included all GLP-1 agonists combined and individual agents (Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide, Tirzepatide)... Different GLP-1 agonists were associated with varying risks for eustachian tube disorders. A history of GLP-1 agonist use, including the specific agent, should be considered when patients present with symptoms related to the eustachian tube."

Clinical • Diabetes • Metabolic Disorders • Otorhinolaryngology

Copeptin Levels at Baseline and in Response to Short-Acting GLP-1 Receptor Agonists in Patients with Endogenous Hyperinsulinemic Hypoglycemia and Healthy Controls - A Secondary Analysis (ENDO 2025) - P=N/A | "Exenatide induced a more pronounced blood glucose decrease in patients, triggering a stronger copeptin response compared to healthy controls, withoutdownregulation from chronic hypoglycemic stress. These findings provide further insights into copeptin dynamics in both chronic and acute hypoglycemic states."

Clinical • Hypoglycemia

Beta cell mass and function in individuals with and without remission of type 2 diabetes after Roux-en-Y gastric bypass (EASD 2025) - P | "In this study, we aimed to compare the differences in beta cell mass in individuals with and without remission of type 2 diabetes after RYGB using [68Ga]Ga-NODAGA-exendin-4 PET/CT imaging.Materials and Age- and BMI-matched individuals with (n=8) and without (n=9) remission of type 2 diabetes up to 4 years after RYGB underwent a combined arginine stimulation test (ARGT) and oral glucose tolerance test (OGTT) to determine beta cell function... Individuals with remission of type 2 diabetes after RYGB have better beta cell function compared to those not achieving remission, although no significant differences in beta cell mass are observed between the groups. Our data argue against a stimulating effect of RYGB on beta cell mass, although potential reactivation of nonfunctional (so-called dormant) beta cells in remitters cannot be excluded."

Bariatric surgery • Clinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Comparison of Long-Acting and Short-Acting GLP-1 Receptor Agonists on Copeptin in Euvolemic Participants - A Secondary Analysis of Three Prospective Trials (ENDO 2025) - "The primary objective was to compare the effect of a three-week treatment with dulaglutide (GOLD & GATE trials) to a single dose of exenatide (FAST trial) on plasma copeptin release in euvolemic adults. Long- and short-acting GLP-1 RA differ in their effects on copeptin regulation. Long-acting GLP-1 agonists significantly suppress copeptin, likely through a synergistic mechanism, while short-acting GLP-1 RAs appear to stimulate copeptin release. These differing effects may also extend to other GLP-1-related mechanisms with potential high clinical relevance."

Clinical

Beta cell mass in individuals with and without hyperinsulinaemic hypoglycaemia after Roux-en-Y gastric bypass (EASD 2025) - P1 | "In this study, we aimed to investigate differences in beta cell mass between individuals with and without postprandial HH after RYGB using [68Ga]Ga-NODAGA-exendin-4 PET/CT imaging.Materials and Individuals with severe postprandial HH (n=10, 8 female; age 40.5 ± 8.7 years; BMI 28.9 ± 3.4 kg/m²) and without HH (n=9, 7 female; age 47.0 ± 4.0 years; BMI 27.9 ± 4.8 kg/m²) after RYGB were included in the study... Our data indicate that expansion of beta cell mass does not explain severe postprandial HH after RYGB, since beta cell mass did not differ between the groups. Dysfunctional insulin secretion of beta cells may explain postprandial HH after RYGB, which requires further elucidation in future studies."

Bariatric surgery • Clinical • Hypoglycemia • Metabolic Disorders

Exenatide for diagnosing endogenous hyperinsulinemic hypoglycemia - a randomized placebo-controlled, double-blind, cross-over proof-of-principle study. (PubMed, Eur J Endocrinol) - P=N/A | "Exenatide is a promising, faster, less cumbersome and less expensive diagnostic tool for EHH compared to the fasting test. Larger trials are warranted to confirm its diagnostic utility."

Journal • Hypoglycemia • Solid Tumor

Accessible Type 2 diabetes medication through stable expression of Exendin-4 in Saccharomyces cerevisiae. (PubMed, Front Syst Biol) - "In this study, experimental models for recombinant Exendin-4 protein production were designed in both Escherichia coli and Saccharomyces cerevisiae. Protein expression in the chromosomally integrated S. cerevisiae strain was observed at the expected size of Exendin-4 and confirmed by immunoassay. This provides a foundation for the use of this Generally Regarded as Safe organism as an affordable treatment for Type 2 diabetes that can be propagated, prepared, and distributed locally."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis. (PubMed, Int J Obes (Lond)) - "GLP-1 RAs showed several adverse gastrointestinal effects in non-diabetic patients with overweight or obesity. Understanding the different risk profiles of GLP-1 RAs helps clinicians make informed treatment decisions by balancing therapeutic benefits with potential side effects."

Adverse events • Journal • Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity

Antidiabetic drugs in Parkinson's disease: a comprehensive meta-analysis on efficacy and safety with trial sequential analysis and GRADE evaluation. (PubMed, Inflammopharmacology) - "GLP-1 agonists revealed potential antidepressant effects as well as improving cognitive functions detected by MADRS and MATTIS-DRS, respectively. However, antidiabetic drugs were associated with higher risks of gastrointestinal adverse effects such as nausea, vomiting, and weight loss."

Journal • Retrospective data • Review • CNS Disorders • Diabetes • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Type 2 Diabetes Mellitus

Frequency, clinical characteristics, and outcomes associated with various definitions of remission after initiation of GLP-1RA for type 2 diabetes management (EASD 2025) - "GLP-1RA were distributed as follows: 50.5% dulaglutide; 24.9% liraglutide; 11.7% semaglutide; 11.0% exenatide; 1.4% lixisenatide. Remission of T2D after initiation GLP-1RA is not a rare event, its frequency and duration varying substantially by remission definition. When achieved, GLP-1RA-induced remission of T2D is associated with durable metabolic improvements up to 4 years and, possibly, fewer cardiovascular events."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Enhancement of a five-drug class model for type 2 diabetes treatment selection to include oral and injectable semaglutide (EASD 2025) - "We assessed the calibration of observed 12-month response with semaglutide versus predicted 12-month HbA1c for non-semaglutide GLP1-RA initiations (liraglutide, dulaglutide, exenatide) from the original five-drug model...We validated the new model using a previously published methodology, which compares predicted versus observed differential treatment effects in patients who initiated the model-predicted optimal therapy (concordant) and those who did not (discordant). There were 2,273 new users of oral semaglutide and 5,114 new users of injectable semaglutide with complete model predictors (mean ± SD baseline characteristics: HbA1c 74.3 ± 13.4 mmol/mol, age 58.6 ± 10.5 years, BMI 36.4 ± 7.3 kg/m2, eGFR 93.0 ± 18.4 ml/min per 1.73m2, 55.2% male)... An extended five-drug class treatment selection model can accurately predict the relative glucose-lowering efficacy of oral and injectable semaglutide versus other drug classes. This enhancement is a..."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The GLP-1 analogue, exendin-4, improves bone material properties and strength through a central relay in ovariectomized mice. (PubMed, Am J Physiol Endocrinol Metab) - "Altogether, these data confirm that GLP-1r agonists represent an interesting approach for managing bone fragility due to ovariectomy, but also suggest that GLP-1r agonists require a central relay-yet to be identified-to exert positive effects on bone physiology. Further studies are needed to decipher the mechanisms of action of GLP-1 and GLP-1r agonists on bone physiology."

Journal • Preclinical • Musculoskeletal Diseases • Orthopedics

Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in a global real-world cohort of people living with type 2 diabetes (EASD 2025) - "Among the GLP-1 RAs group, 36.8%, 29.4%, 24.0%, and 9.9% initiated dulaglutide, liraglutide, semaglutide, and exenatide, respectively. In a global real-world cohort of people living with T2D without evidence of neurodegeneration, the initiation of GLP-1 RAs, compared to DPP4i or basal insulin, was associated with a lower risk of new-onset neurodegeneration."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Post-weaning protein restriction impairs glucagon-like peptide 1 action and leads to pancreatic islet atrophy in mice (EASD 2025) - "Isolated islets from the R group hyposecreted insulin at 11.1 mM glucose (0.45 ± 0.06 ng/islet.h) and when associated with a GLP-1R agonist, exendin 4 (0.7 ± 0.1 ng/islet.h) compared to C (0.65 ± 0.06 and 1.1 ± 0.2 ng/islet.h ng/islet.h)... Protein undernutrition augmented glucose tolerance, possibly due to increased insulin sensitivity, despite pancreatic islet hypotrophy and diminished insulin secretion from isolated islets. Furthermore, pancreatic beta-cell insulin secretion in R mice was impaired in response to incretin stimulation, probably caused by diminished GLP-1 receptor gene expression in pancreatic islets."

Late-breaking abstract • Preclinical • Metabolic Disorders

Glucolipotoxicity affects the beta cell functional network by reducing leader and hub cell function: effects GLP1 receptor agonism (EASD 2025) - "Subsequently, 1nM exendin-4 (GLP-1 analogue) was introduced... Our results suggest that glucolipotoxicity selectively affects the creation of a functional network responsible for the generation and the spreading of pulsatile intracellular Ca2+ waves during the second phase of insulin secretion. In conclusion, changes observed here in beta cell connectivity might contribute to defective insulin secretion in T2DM and in some cases may be reversed by GLP-1 receptor agonism."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Does postnatal depletion of 14-3-3zeta enhance functional beta cell mass? (EASD 2025) - "β-cell proliferation is influenced by various mitogenic stimuli [eg. high-fat diet (HFD), Exendin-4 (Ex-4)] and regulated by the nuclear translocation of Cyclin-CDK complexes... Altogether, acute depletion of 14-3-3ζ via GLP-1-ASOYwhaz increases β-cell proliferation. However, the absence of a HFD-induced mitogenic response and negative metabolic phenotypes suggest that this approach is not suitable to investigate the effects of postnatal 14-3-3ζ depletion on β-cell proliferation."

Diabetes • Metabolic Disorders • PCNA • YWHAZ

Tirzepatide prevents palmitate-induced apoptosis, autophagy, and senescence in human cardiac progenitor cells (EASD 2025) - "Defective hCPC number and pro-angiogenic capacity contribute to diabetes- and obesity-related heart failure in humans...Conversely, the GLP-1R agonist exendin-4 prevented palmitate-induced apoptosis and autophagy, whereas GIP prevented apoptosis, but not autophagy. hCPC express functional GLP-1R and GIPR. hCPC express functional GLP-1R and GIPR. Tirzepatide prevents palmitate-induced apoptosis, autophagy, and senescence of hCPC. Hence, in humans, pharmacological targeting through GLP-1R and GIPR might produce beneficial cardiovascular effects that go beyond glucose control and weight loss."

Metabolic Disorders • Obesity • CASP3 • CDKN1A

Impact of the recessive HNF1A p.A251T variant on insulin secretion in patient-derived and genome-edited stem cell-derived beta cells (EASD 2025) - "When exposed to high glucose and the GLP-1 receptor agonist Exendin-4, or Glibenclamide (GLB), A251T cells exhibited higher insulin secretion compared to high glucose alone (Exendin-4: 0.1% vs 0.3% total, GLB: 0.2% vs 0.3%; both p < 0.001). We provide a detailed analysis of a recessive HNF1A variant associated with monogenic diabetes. Our data are consistent with the view that that the A251T variant leads to mild loss of function, leading to impaired Ca²⁺ dynamics, and consistent with the observation of diabetes only in homozygous carriers. Importantly, defective glucose-induced insulin secretion from patient-derived SC-β cells was partially rescued with exendin-4, suggesting that GLP-1R agonists may be useful therapeutically."

Clinical • Diabetes • Metabolic Disorders • HNF1A • KLF4 • MYC • POU5F1 • SOX2

Pancreatic adipocytes modulate insulin secretion and incretin responsiveness of human beta cells (EASD 2025) - "PAT has divergent effects on beta cells, promoting glucose- and incretin-augmented insulin secretion in ND individuals while triggering dysfunctional GSIS in T2D. Our observations suggest that PAT interferes with incretin signalling pathways in beta cells, opening new avenues for modulation of insulin secretion."

Metabolic Disorders • Type 2 Diabetes Mellitus • PPARG

Interaction between pancreatic volume, pancreatic fat infiltration and beta cell mass (EASD 2025) - "In this study, we aimed to investigate the interplay between pancreatic volume, IPFD and beta cell mass using [68Ga]Ga-NODAGA-exendin-4 PET/CT imaging in a large variety of individuals either with or without type 2 diabetes or other metabolic disturbances.Materials and This posthoc analysis included 52 individuals: 25 with type 2 diabetes, 7 with remission of type 2 diabetes after Roux-en-Y gastric bypass (RYGB), 8 without remission of type 2 diabetes after RYGB, 3 without type 2 diabetes and 9 without (a history of) type 2 diabetes who underwent RYGB... Our data indicate that a smaller pancreas accompanied by pancreatic fat accumulation is associated with lower beta cell mass, which contributes to impaired insulin secretion and thereby an increased risk of type 2 diabetes."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Cranio-GLP1: efficacy and safety of GLP1 analogue treatments in patients with craniopharyngiomas (EASD 2025) - "A total of 77% received Semaglutide, 43% Liraglutide, 18% Exenatide, and 14% Dulaglutide. This real-world retrospective study demonstrates that aGLP-1 treatments lead to moderate but significant weight loss in adult oCP patients. The efficacy appears lower than in common obesity, and predictive factors for treatment response remain unclear. Managing adverse effects, particularly gastrointestinal issues, is crucial to limiting treatment discontinuation."

Clinical • Metabolic Disorders • Obesity

ADO12, a non-fibrotic encapsulation system enables stem cell-derived islets in vivo maturation for type 1 diabetes treatment (EASD 2025) - "They were then encapsulated in ADO12 and evaluated in vitro by glucose and exenatide insulin stimulated secretion assay (GSIS)... The ability of SCDI to mature in ADO12 was demonstrated in vivo, a step towards treatment of type 1 diabetes with SCDI without requiring immunosuppression."

Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

GLP-1 receptor agonists (GLP-1RAs) protect against hepatocyte senescence (EASD 2025) - "This study investigates GLP-1 and GLP-1RA Exendin-4 (Ex4) role in counteracting hyperinsulinemia-induced hepatocyte senescence, highlighting their potential for treating fatty liver disease.Materials and Human hepatocytes were chronically exposed to hyperinsulinemia to induce senescence, followed by treatment with Ex4 or GLP-1 for 24h... In conclusion, Ex4 and GLP-1 reduce hyperinsulinemia-induced hepatocyte senescence, likely via AMPK activation, supporting their potential as treatments for NAFLD/NASH and related metabolic complications."

Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • CXCL8 • DPP4 • IL18 • MMP3 • ZMAT3

Impact of glucagon-like peptide-1 receptor agonism on beta cell Ca2+ dynamics within the pancreatic islet in vivo (EASD 2025) - "Critically, acute intraperitoneal injection of exendin-4 (Ex-4, 1 nmol/kg) at day 8 restored islet Ca2+ dynamics in HFHS and GckKI+ animals (Ctrl+PBS vs Ctrl+Ex-4 not significant, n=4, HFD+PBS vs HFD+Ext-4 p=0.013, n=7, GckKI++PBS vs GckKI++Ext-4, p=0.016, n=5)... By developing an approach to follow the activity of individual beta cells prospectively over time in the living animal we show that leader and hub subpopulations are functionally stable subpopulations in vivo. Hyperglycemia disconnected islet-wide functional network by disturbing primarily the hub beta-cells in vivo. This effect was reversed acutely by GLP1R agonism, likely contributing to improved insulin secretion."

Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus