avexitide (exendin 9-39) / Amylyx - LARVOL DELTA

ORAL ADMINISTRATION OF ALLULOSE ATTENUATES CISPLATIN-INDUCED AKI VIA GLP-1 RELEASE (ISN-WCN 2026) - "Moreover, the renoprotection was partially canceled by exendin (9-39) administration and completely canceled in Glp1r global knock out mice.Conclusion Oral administration of allulose has renoprotective effect for cisplatin-induced AKI probably through the release of GLP-1. Further studies including vagal afferent ablation will be needed to elucidate the precise mechanism."

Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury

Dendrobium huoshanense stem polysaccharide protects against Alzheimer's disease by modulating SCFAs/GLP-1 axis-mediated neuroinflammation suppression. (PubMed, Int J Biol Macromol) - "However, the treatment of exendin 9-39, a GLP-1 receptor antagonist, weakened the protective effect of cDHPS against AD, and the depletion of SCFAs reversed the beneficial effects of cDHPS on cognitive dysfunction, hippocampal neuronal injury, neuroinflammation, and GLP-1 secretion in AD mice. These results suggest that cDHPS could protect against AD by modulating the SCFAs/GLP-1 axis-mediated neuroinflammation suppression."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • CASP1 • NLRP3

LUCIDITY: Avexitide for Treatment of Post-Bariatric Hypoglycemia (clinicaltrials.gov) - P3 | N=75 | Active, not recruiting | Sponsor: Amylyx Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hypoglycemia

Potential treatment benefits of a GLP-1R antagonist in combination with immune checkpoint inhibitors in colorectal cancer. (PubMed, Oncol Lett) - "The present study aimed to evaluate the antitumor effects of the GLP-1R antagonist Exendin 9-39 (Exe-9) combined with anti-programmed cell death protein-1 (PD-1) treatment in preclinical CRC models...Furthermore, combination therapy with the GLP-1R antagonist and anti-PD-1 yielded an improved antitumor effect compared with either treatment alone, and high GLP-1R ex2pression in clinical samples correlated with poor ICI response. These findings suggest that GLP-1R antagonism potentiates T-cell-mediated antitumor immunity and may provide a promising adjunctive therapeutic strategy for patients with CRC when combined with ICIs in the future."

Checkpoint inhibition • IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Intestinal interleukin-22 enhances GLP-1 production via the STAT3 pathway to improve glucose homeostasis during high-fat diet induced obesity in a study with male mice. (PubMed, Nat Commun) - "Conversely, the GLP-1 receptor antagonist exendin-9-39 abolished the glucose-lowering effects of IL-22, demonstrating that IL-22 acts primarily through GLP-1-dependent pathways. These findings identify IL-22 as an important regulator of intestinal GLP-1 production and glucose homeostasis during diet-induced obesity and highlight IL-22-GLP-1 signaling as a potential therapeutic axis for metabolic disorders."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • GCG • IL22 • STAT3

O-Acetyl-Serine Supplementation Enhances Insulin Secretion and Improves Postprandial Glycaemia in Lean and Prediabetic Mice. (PubMed, FASEB J) - "However, in vivo treatment with the GLP-1 receptor antagonist exendin (9-39) revealed that GLP-1 signaling only partially mediates OAS's effects, consistent with OAS direct action on insulin secretion...This improvement was associated with increased postprandial insulin and GLP-1 levels. Together, these findings identify OAS as a glucose-dependent insulin secretagogue with therapeutic potential to enhance insulin secretion and prevent progression from prediabetes to T2D."

Journal • Preclinical • Metabolic Disorders • Type 2 Diabetes Mellitus

The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Mayo Clinic | Initiation date: Dec 2025 ➔ Oct 2026

Trial initiation date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

EX-HYPO: The Effect of Endogenous GLP-1 on Glucagon Secretion in Type 1 Diabetes (clinicaltrials.gov) - P=N/A | N=12 | Recruiting | Sponsor: Asger Lund, MD

New trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Endogenous Glucagon-Like Peptide 1 Enhanced by Vildagliptin Reduces Triglyceride Appearance During Intraduodenal Fat Infusion in Type 2 Diabetes. (PubMed, Diabetes) - "Fifteen participants with T2D, managed by diet and/or metformin, were studied on three occasions in a double-blind, randomized, crossover design. Vildagliptin selectively reduced TG(54:4) and TG(54:5) species, whereas exendin(9-39) increased total TGs and 10 individual TG species. The implications of our finding are that endogenous GLP-1 plays a physiological role in the regulation of postprandial lipid handling in T2D."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study to Evaluate the Effect of Genetic Variation on Beta-cell Function During Fasting and Hyperglycemia in Nondiabetics (clinicaltrials.gov) - P3 | N=21 | Completed | Sponsor: Adrian Vella | Recruiting ➔ Completed | N=40 ➔ 21

Enrollment change • Trial completion

The Role of Islet GLP-1 in the Pathogenesis of Prediabetes (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Metabolic Drug, Electrophysiological Savior: Unmasking GLP-1RA's Novel Therapeutic Target in Sinoatrial Node Dysfunction (AHA 2025) - "This study identifies Supaglutide as the first GLP-1RA capable of restoring SAN electrophysiology via oxidative and calcium signaling regulation, beyond glucose control. These findings not only uncover a novel function of GLP-1RA beyond metabolic regulation but also suggest that targeting SAN-specific mechanisms may represent a broader therapeutic strategy for arrhythmogenic cardiac diseases, especially those associated with metabolic disorders."

Late-breaking abstract • Cardiovascular • Diabetes • Fibrosis • Heart Failure • Immunology • Inflammation • Metabolic Disorders • CAMK2D • CD86 • RYR2 • SIRT3 • TNFA

Developing 68Ga-Labeled Exendin(9-39) Derivatives for PET Imaging of Insulinomas. (PubMed, Bioconjug Chem) - "These findings highlight the power of combining computational screening with systematic experimental validation. In conclusion, [68Ga]Ga-E09 demonstrates superior binding affinity, cellular uptake, and imaging performance, suggesting its potential as a promising agent warranting further studies."

Journal • Hypoglycemia • Oncology • Pediatrics • Solid Tumor

Linking GLP-1 activation with steroidogenesis, redox, endoplasmic reticulum stress, mitophagy, and the apoptotic regulatory network unlocks the emerging impacts of semaglutide on 5-fluorouracil-induced testicular toxicity. (PubMed, Life Sci) - "This study highlighted the use of Sema as adjunctive therapy in the 5-FU treatment protocol to guard against the associated testicular dysfunction, via modulating oxidative stress, ERS, and mitochondrial dysfunction in the rat experimental model."

Journal • Metabolic Disorders • Oncology • ATF6 • DAZL • HSPA5

Acute effects of GIP and GLP-1 receptor antagonism in totally pancreatectomized individuals: A randomized double-blind, placebo-controlled crossover study. (PubMed, Diabetes Obes Metab) - "Endogenous GIP contributes to the regulation of postprandial bone resorption independently of pancreatic factors. In contrast, GIP receptor and/or GLP-1 receptor antagonism had no measurable effects on glucose metabolism, gastric emptying, appetite, food intake, triglycerides, or haemodynamics, supporting a pancreatic contribution to some of these effects of the endogenous hormones, although the surgical reconstruction may have influenced the sensitivity of the targets."

Journal • Diabetes • Metabolic Disorders

The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Mayo Clinic | Initiation date: Sep 2025 ➔ Dec 2025

Trial initiation date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Fatty acid transport protein-2 inhibition enhances glucose tolerance through α-cell-mediated GLP-1 secretion. (PubMed, J Clin Invest) - "Direct evidence of FATP2KO-induced α-cell-mediated glucagon-like peptide-1 (GLP-1) secretion included increased GLP-1-positive α-cell mass in FATP2KO db/db mice, small molecule FATP2 inhibitor enhancement of GLP-1 secretion in αTC1-6 cells and human islets, and exendin[9-39]-inhibitable insulin secretion in FATP2 inhibitor-treated human islets. FATP2-dependent enteroendocrine GLP-1 secretion was excluded by demonstration of similar glucose tolerance and plasma GLP-1 concentrations in db/db FATP2KO mice following oral versus intraperitoneal glucose loading, non-overlapping FATP2 and preproglucagon mRNA expression, and lack of FATP2/GLP-1 co-immunolocalization in intestine. We conclude that FATP2 deletion or inhibition exerts glucose-lowering effects through α-cell-mediated GLP-1 secretion and paracrine ß-cell insulin release."

Journal • Diabetes • Diabetic Nephropathy • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • SLC27A2

The effect of GLP-1 receptor antagonists and agonists on islet function in non-diabetic subjects with the GLP1R polymorphism at rs3765467 (EASD 2025) - P3 | "The T allele at rs3765467 increases responsiveness of GLP1R to its endogenous ligand. These effects are relevant to the fasting state and less apparent when the islet is stimulated by hyperglycemia or liraglutide."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Glucagon-like Peptide 1, Glucose Metabolism and Gastric Bypass (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date

The Effects of Bariatric Surgeries on Glucose Metabolism (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Hypoglycemia

Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Trial primary completion date: Aug 2025 ➔ Aug 2026 | Trial completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Hypoglycemia

Population PK (PopPK) and Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis of Avexitide in Individuals with Post-Bariatric Hypoglycemia (ENDO 2025) - "Mechanistically, Cmin is expected to be a primary driver of avexitide efficacy. Avexitide 90 mg once daily resulted in Cmin above EC50 for 24 hours, providing evidence that this dose can have continued biological effect between daily doses and further supporting the rationale for and appropriateness of the 90 mg once daily dosing regimen in the Phase 3 LUCIDITY trial."

Clinical • PK/PD data • Hypoglycemia

Reduction in Rate of Hypoglycemic Events with Avexitide in Post-Bariatric Hypoglycemia: Results from the Phase 2 and 2b Studies (ENDO 2025) - "Avexitide 30 mg BID and 60 mg QD led to a 40% and 55% reduction in the composite rate of Level 2&3 events, respectively. The impact of avexitide on composite rates of Level 2&3 hypoglycemia in the phase 2b trial, including at the higher 90 mg QD dose being tested in LUCIDITY, will be presented. Results of the complete analysis will provide valuable context given the planned LUCIDITY trial, which has topline data anticipated in 1H 2026."

P2 data • CNS Disorders • Epilepsy • Gastrointestinal Disorder • Hypoglycemia

Reduction in Rate of Hypoglycemic Events with Avexitide in Post-Bariatric Hypoglycemia: Results from the Phase 2 and 2b Studies (ENDO 2025) - "Avexitide 30 mg BID and 60 mg QD led to a 40% and 55% reduction in the composite rate of Level 2&3 events, respectively. The impact of avexitide on composite rates of Level 2&3 hypoglycemia in the phase 2b trial, including at the higher 90 mg QD dose being tested in LUCIDITY, will be presented. Results of the complete analysis will provide valuable context given the planned LUCIDITY trial, which has topline data anticipated in 1H 2026."

P2 data • CNS Disorders • Epilepsy • Gastrointestinal Disorder • Hypoglycemia