Byetta (exenatide) / AstraZeneca - LARVOL DELTA

Role of Sodium-Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review. (PubMed, touchREV Endocrinol) - "Canagliflozin, empagliflozin, dapagliflozin and licogliflozin were studied either as monotherapy or in combination with metformin or exenatide. Adverse effects with SGLT2i were mostly mild and included genital infections. SGLT2i, when used as monotherapy or combined with metformin or GLP1RA, are a promising therapy for improving metabolic and hormonal parameters in PCOS."

Journal • Review • Dyslipidemia • Infectious Disease • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome • Women's Health

CARDIOVASCULAR OUTCOMES AND MORTALITY ASSOCIATED WITH GLP-1 RECEPTOR AGONISTS IN INFLAMMATORY MYOSITIS AND NECROTIZING MYOPATHY: A RETROSPECTIVE COHORT STUDY (EULAR 2025) - "The cohort with GLP-1 RA use (n = 3,066) included patients treated with Exenatide, Dulaglutide, Liraglutide, Semaglutide, Tirzepatide, or Lixisenatide, while the comparator cohort without GLP-1 RA use (n = 57,788) included patients not receiving these therapies. Propensity score matching (PSM) was conducted to adjust for baseline differences, including demographics (age, sex, ethnicity), comorbidities (hypertension, diabetes, obesity, smoking), and medication use (statins, insulin, corticosteroids, SGLT2 inhibitors, methotrexate, rituximab)...Comorbidities such as hypertension (73.6% vs. 25.8%), diabetes (71.1% vs. 14.4%), and obesity were more prevalent, and medication use, including aspirin (44.2%) and metformin (56.8%), was also higher... GLP-1 RA is associated with significant reductions in mortality and cardiovascular events in patients with inflammatory myositis and necrotizing myopathy. These findings suggest that GLP-1 RAs may be a valuable adjunctive therapy for..."

Retrospective data • Cardiovascular • Dermatomyositis • Diabetes • Genetic Disorders • Hypertension • Immunology • Inflammation • Metabolic Disorders • Myocardial Infarction • Myositis • Obesity • Venous Thromboembolism

One-step, automated radiosynthesis of new and established “Silicon-[18F]Fluoride Acceptor”-based neuroendocrine tumor imaging agents (SNMMI 2025) - "NDC-RCY of [18F]SiTATE was 43% (52% DC; n=1) using TEAOTs and 49±7% (60±9% DC; n=3) using TBADP. For the TBADP runs, activity yield was 82±14 mCi, starting from 167±8 mCi. Total synthesis time was 25 min."

Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

One-step, automated radiosynthesis of new and established “Silicon-[18F]Fluoride Acceptor”-based neuroendocrine tumor imaging agents (SNMMI 2025) - "NDC-RCY of [18F]SiTATE was 43% (52% DC; n=1) using TEAOTs and 49±7% (60±9% DC; n=3) using TBADP. For the TBADP runs, activity yield was 82±14 mCi, starting from 167±8 mCi. Total synthesis time was 25 min."

Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

GLP-1 agonists in glycemic and weight control of type 2 diabetes. New perspectives. (PubMed, Med Clin (Barc)) - "Since the introduction of exenatide in 2005, more effective drugs have been developed that improve glycemic control, reduce weight, and decrease the occurrence of cardiovascular events. This article discusses the mechanisms of action and efficacy of these agents, highlighting recent advances such as polyagonists and oral formulations."

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

Long-Acting Exendin 4 Protein Enhances Insulin Secretion and Improves Steatotic Liver in High-Fat Diet–Fed Mice (ADA 2025) - "Collectively, these findings suggest that EX-ABD-AFF enhances insulin release in pancreatic β-cells and that hepatic LCN2 may play a role in improving steatotic liver."

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

GLP-1 Receptor Agonists Induce Lasting Cyclic-AMP Generation and Insulin Secretion in Beta Cells (ADA 2025) - "This study investigated the mechanisms underlying these differences, with a focus on cAMP, the crucial second messenger involved in incretin-induced potentiation of insulin secretion. Islets from mice expressing a genetically encoded cAMP sensor in beta cells were perfused with GIP and GLP-1 receptor (GLP-1R) agonists (GLP-1, exendin-4, and semaglutide), and kinetics of cAMP levels and glucose-stimulated insulin secretion were assessed. Acute GIP treatment induced a transient cAMP response that dissipated with peptide washout. These data show that beta cells respond with distinct kinetics of cAMP generation in response to different incretins, with GLP-1R agonists capable of triggering lasting cAMP generation and insulin secretion. These findings reveal the mechanism(s) that underlie the effectiveness of incretin-based drugs."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Oral Small Molecule GLP-1 Receptor Agonist Demonstrates Beneficial Effects in Parkinson's Disease–Like Model Using Humanized GLP-1R Mice (ADA 2025) - "Exendin-4, a GLP-1 receptor (GLP-1R) agonist peptide, has shown beneficial effects in preclinical PD models; however the effects of small molecule GLP-1R agonists in preclinical PD-like models remain unclear... These findings suggest this oral small molecule GLP-1R agonist showed neuroprotective effects by mitigating motor deficits and preserving DA neuron in MPTP-induced PD model. This highlights a potential benefit in Parkinson's disease."

Late-breaking abstract • Preclinical • Metabolic Disorders

Silencing of Mitochondrial Transaminase GPT2 in β-Cells Enhances Response to Antidiabetic Incretins (ADA 2025) - "Silencing GPT2 enhanced β-cell sensitivity to the GLP-1 receptor agonist Exendin4 (Ex4) (1.6 and 2.6-fold in ND and T2D islets, respectively, P≤0.01)... GPT2 depletion enhances incretin sensitivity and supports β-cell survival, raising it as a therapeutic target to mitigate β-cell dysfunction in T2D"

Metabolic Disorders • Type 2 Diabetes Mellitus

The Molecular Basis of Survodutide (BI456906) Glucagon/GLP-1 Receptor Dual Agonism (ADA 2025) - "Cryogenic electron microscopy (cryo-EM) structures of GCGR and GLP-1R in complex with Survo and G protein were determined at high resolution. Survo is a 29 amino acid (AA) peptide based on GCG with pos 18, 20 and 23 swapped to GLP-1 and pos 16 swapped to exendin-4. The activation profile of Survo at GCGR and GLP-1R can be rationalized by structural evidence and the gained knowledge will inform therapeutic approaches in both obesity and MASH targeted treatment regimes. We further give insight into the effect of peptide lipidation."

Late-breaking abstract • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • GCG

Impact of Glucagon-Like Peptide 1 Receptor (GLP-1R) Agonism on β-Cell Ca2+ Dynamics within the Pancreatic Islet In Vivo (ADA 2025) - "Acute intraperitoneal exendin-4 (Ex-4, 1 nmol/kg) administration 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)... An effect of hyperglycemia to disconnect islet-wide functional networks in vivo is rapidly reversed by GLP1R agonism, likely contributing to improved insulin secretion. The actions of Ex-4 were more marked than usually observed in vitro, possibly implicating neuron-mediated signal relay to the β-cell from remotely-located GLP1R (e.g. in the gut, brain)."

Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Single-Dose GLP-1–Based Pancreatic Gene Therapy Prevents Obesity and Diabetes in High-Fat–Fed Mice (ADA 2025) - "Here, we assessed the potential for PGTx to prevent metabolic disease progression in lean and diet-induced obesity (DIO) mice. We created an AAV vector encoding Exendin-4 with an insulin promoter for beta-cell-specific expression... These data suggest that PGTx can durably reduce weight and glycemia in DIO and prevent weight gain and hyperglycemia when treatment is initiated before HFD. Lean mice receiving PGTx exhibited less weight loss than their DIO counterparts, suggesting a self-limiting mechanism that could enhance the PGTx safety profile."

Gene therapy • Late-breaking abstract • Preclinical • Diabetes • Metabolic Disorders • Obesity

Human Fatty Pancreas In Vitro Model Reveals Specific Effects on Beta-Cell Function and Incretin Responsiveness in T2D (ADA 2025) - "Outcomes included adipogenesis (RT-qPCR), glucose-stimulated insulin secretion (GSIS), and response to incretins (Exendin-4, GIP, Tirzepatide). T2D-derived PAT organoids showed impaired adipogenesis and increased lipolysis compared to ND-derived organoids. PAT has divergent effects on beta-cell function, exacerbating dysfunction in T2D while enhancing or protecting function in ND individuals. Our co-culture model provides a valuable platform for investigating the role of PAT-islet interaction in T2D pathophysiology."

Preclinical • Metabolic Disorders • Type 2 Diabetes Mellitus

Tirzepatide Prevents Palmitate-Induced Apoptosis, Autophagy, and Senescence in Human Cardiac Progenitor Cells (ADA 2025) - "hCPC express functional GLP-1R and GIPR that mediate partially overlapping bioeffects. Tirzepatide prevents palmitate-induced apoptosis, autophagy, and senescence of hCPC, showing that dual pharmacological targeting through both GLP-1R and GIPR might be required to exert full beneficial effects on hCPC survival and function."

Metabolic Disorders • Obesity • CASP3 • CDKN1A

Disparities in Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA) Utilization in Pediatric Type 2 Diabetes (T2D) (ADA 2025) - "Multivariable logistic regression was used to assess associations of GLP-1 RA prescription ever prescribed (yes/no) with race/ethnicity and potential confounders (age, sex, obesity, co-morbidities, and use of metformin or insulin). Among 4000 youths (57.7 % female, 33.1% NH White, 47.2% NH Black, 13.0% Hispanic, 6.7% Other, mean age: 14.9 y [SD 1.9]), GLP-1 RAs were prescribed in 23.3% (liraglutide 17.5%, dulaglutide 4.4%, exenatide 2.3%, semaglutide 2.2%) and less frequently than metformin (73.8%) and insulin (64.0%). Among Medicaid-insured youths with T2D, Hispanic youths were less likely to be prescribed GLP-1 RAs. Developing strategies to ensure equitable access to novel treatments in pediatric T2D are needed."

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

Cellular Characterisation of Signalling and Receptor Trafficking Induced by MET-097, a G Protein-Biased GLP-1R Agonist (ADA 2025) - "We aimed to further elucidate the signalling and trafficking profile of MET-097. In vitro BRET-based biosensors were used to compare clinically relevant GLP-1R agonists. Compared to reference agonists (GLP-1/exendin-4/semaglutide), MET-097 acted as a partial agonist for Gαs and Gαq recruitment at both the plasma membrane (36% and 22% of exendin-4) and endosomal compartments (34% and 37% of exendin-4), yet still showed full cAMP response (115% of exendin-4). We speculate the pharmacological attributes of MET-097 may contribute to a unique pharmacodynamic profile. Of particular interest will be to align these attributes with the efficacy and tolerability observed in clinical trials."

Metabolic Disorders • Obesity • ARRB1

Sex-Dependent Additive Effects of Dorzagliatin and Incretin on Insulin Secretion in a Novel Mouse Model of GCK-MODY (ADA 2025) - "Combined treatment with GKA and incretin may thus be useful in GCK-MODY or GCK-PNDM, and possibly in more common forms of type 2 diabetes."

Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin Sensitivity Dependent and Insulin Sensitivity Independent Insulin Secretion in Nondiabetic Individuals (ADA 2025) - "incretin-stimulated insulin secretion is unrelated to the prevailing level of insulin sensitivity and is impaired in subjects with prediabetes."

Clinical • Metabolic Disorders • Type 2 Diabetes Mellitus

Elucidating the Benefit of Pump-Delivered Subcutaneous GLP-1R Agonist—Exploratory Study in the DIO Mouse (ADA 2025) - "We evaluated pump-delivered GLP-1Ra as an alternate treatment approach. We conducted a 28d study of continuous pump-delivered subcutaneous (SC) short-acting GLP-1Ra (exenatide) in diet-induced obese (DIO) mice (n=60; post-21-week high-fat diet, 60% kcal)... Pump-delivered GLP-1Ra exhibits favorable body weight and glycemic effects in DIO mice, with a less abrupt initial suppression of food intake than SEMA. Bolus GLP-1Ra also reduced post-caloric challenge glycemic excursion. GLP-1Ra delivered by a basal-bolus pump may represent an alternative for patients seeking GLP-1Ra clinical benefit with greater dosing flexibility."

Preclinical • Diabetes • Metabolic Disorders • Obesity

Association between Preoperative GLP-1RA Use and Postoperative Respiratory Complications in Real-World Patients Undergoing Elective Surgical Procedures—A Target Trial Emulation Study (ADA 2025) - "Preoperative GLP-1 RA use was associated with increased postoperative respiratory complications compared to non-users."

Clinical • Real-world • Real-world evidence • Metabolic Disorders • Obesity

Cardiovascular Outcomes Associated with Dulaglutide, Exenatide, Liraglutide, and Semaglutide in Adults with Type 2 Diabetes at Moderate Cardiovascular Risk (ADA 2025) - "Semaglutide may be the GLP-1RA associated with the greatest cardiovascular risk reduction in patients with T2D at moderate CVD risk."

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

Beta-Cell Preservation with Early Oral Antidiabetic Medications in Prediabetes (PreDM) (ADA 2025) - "At baseline, subjects received an OGTT and two-step hyperglycemic clamp (+125 and 400 mg/dl) followed by exenatide infusion to quantitate insulin sensitivity (Matsuda Index), insulin secretion (ΔI/ΔG), and beta cell function (disposition index). Subjects then were randomized to receive 24 months of treatment with: (i) Dapagliflozin (DAPA), (ii) Metformin (MET), (iii) Pioglitazone (PIO), or (iv) Saxagliptin (SAXA)... Early pharmacological treatment can prevent progression of PreDM to T2D. DAP and MET improved insulin sensitivity with net weight loss. Despite weight gain, PIO improved total body and adipose insulin sensitivity and robustly increased beta cell function."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Prevascularization Strategies for Subcutaneous Islet Transplantation: Comparative Assessment of BFGF-Loaded Agarose Rods and Bioabsorbable Collagen-Gelatin Sheets (IPITA 2025) - "Histological analysis confirmed islet engraftment in both groups, and 111In-exendin-4-based SPECT/CT imaging demonstrated the successful subcutaneous engraftment of the transplanted islets in both groups. This study demonstrated that both bFGF-containing agarose rods and bioabsorbable collagen–gelatin sheets successfully facilitated syngeneic subcutaneous islet transplantation, indicating that both methods effectively induce prevascularization and support islet engraftment. Given these promising results, further studies on allogeneic subcutaneous islet transplantation are warranted to explore the potential clinical applications of prevascularization strategies."

Transplantation • FGF

AdoShell®, a Nonfibrotic Encapsulation System, Enables Stem Cell-Derived Islets In Vivo Maturation for T1DM Treatment (ADA 2025) - "They were then encapsulated in AdoShell® and evaluated in vitro by glucose and exenatide stimulated secretion assay (GSIS).AdoShell® SCDI were implanted in 3 NXG mice for 4 months, and explants were analyzed by GSIS, total insulin content, histology and immunohistochemistry. Encapsulation of SCDI maintained in vitro functionality, insulin secretion level and intracellular content compared to naked SCDI.In vivo, encapsulated SCDI showed a steady increase in human C-peptide secretion over 2 to 3 months and reached a plateau, a kinetic comparable to published maturation phenotypes.After 132 days in vivo, explanted encapsulated SCDI showed increase of insulin secretion (3-fold), secretion indexes (1.5-fold), and total insulin content (2.4-fold) compared to pre-implantation levels. The ability of SCDI to mature in AdoShell® was demonstrated in vivo, a step towards treatment of type 1 diabetes with SCDI without requiring immunosuppression."

Preclinical • Metabolic Disorders • Type 1 Diabetes Mellitus

GLP-1 Receptor Agonists Induce Lasting Cyclic-AMP Generation and Insulin Secretion in Beta Cells (ADA 2025) - "This study investigated the mechanisms underlying these differences, with a focus on cAMP, the crucial second messenger involved in incretin-induced potentiation of insulin secretion. Islets from mice expressing a genetically encoded cAMP sensor in beta cells were perfused with GIP and GLP-1 receptor (GLP-1R) agonists (GLP-1, exendin-4, and semaglutide), and kinetics of cAMP levels and glucose-stimulated insulin secretion were assessed. Acute GIP treatment induced a transient cAMP response that dissipated with peptide washout. These data show that beta cells respond with distinct kinetics of cAMP generation in response to different incretins, with GLP-1R agonists capable of triggering lasting cAMP generation and insulin secretion. These findings reveal the mechanism(s) that underlie the effectiveness of incretin-based drugs."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus