survodutide (BI 456906) / Zealand Pharma, Boehringer Ingelheim - LARVOL DELTA

Sustained improvements in non-invasive biomarkers with the novel glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide: longitudinal analysis from a phase 2 trial in people with metabolic dysfunction-associated steatohepatitis and fibrosis (EASL 2025) - No abstract available

Biomarker • Non-invasive • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Survodutide activates cAMP signaling and reduces steatosis and fibrosis through its glucagon component in human liver spheroids (EASL 2025) - "Survodutide showed increased cAMP signalling in spheroids as a model for healthy and MASLD human hepatocytes, while the incretin analogues semaglutide and tirzepatide did not show a response. Survodutide significantly lowered triglyceride as well as PC-1 secretion in MASH spheroids. Human liver spheroids represent a robust in vitro model for human liver cells to study glucagon receptor agonism."

Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Sustained improvements in non-invasive biomarkers with the novel glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide: longitudinal analysis from a phase 2 trial in people with metabolic dysfunction-associated steatohepatitis and fibrosis (EASL 2025) - P2 | "Participants who received survodutide vs PBO had significant improvement in multiple non-invasive biomarkers for MASH and liver fibrosis (ELF score and its components, PRO-C3, glucagon, and FIB-4) and significantly reduced levels of total CK18, suggesting increased hepatocyte survival with survodutide treatment."

Biomarker • Non-invasive • P2 data • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • KRT18

Survodutide, a glucagon/GLP-1 receptor dual agonist, in people with MASH with moderate-to-advanced liver fibrosis (stage F2-F3): rationale and design of an event-driven, multinational, randomised, placebo-controlled, phase 3 trial (LIVERAGETM ) (EASL 2025) - P3 | "The phase 3 LIVERAGETM trial will elucidate the long-term effects of survodutide on steatohepatitis, fibrosis, liver outcomes, and all-cause mortality in people with fibrotic MASH without cirrhosis, as well as its tolerability and safety."

Clinical • Metastases • P3 data • Cardiovascular • Diabetes • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Portal Hypertension • Solid Tumor • Type 2 Diabetes Mellitus

Weight dependent, weight independent and non-pharmacological effects on fibroblast activity in metabolic dysfunction associated steatotic liver disease (MASLD) (EASL 2025) - "A weight loss study using VLCD, and data from pharmacological interventions with Resmetirom, GLP1RA and Survodutide previously analyzed for changes in either PRO-C3 and PRO-C6. Pharmacological and non-pharmacological induction of weight loss results in different deactivation of fibroblasts activities, which may have divergent efficacy on heart and liver related outcomes. Furthermore, weight dependent and independent mechanisms of deactivation fibroblasts may result in additional effects on bone and muscle. This understanding may be needed when designing the optimal intervention strategy, including possible combination regimens, for the individual MAFLD patient."

Cardiovascular • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Osteoporosis • FGF19 • FGF21

Non-invasive markers to predict biopsy response in people with metabolic dysfunction-associated steatohepatitis and fibrosis: exploratory analysis of a phase 2 trial of glucagon receptor/glucagon-like peptide-1 receptor dual agonist, survodutide (EASL 2025) - P2 | "We found evidence for predictive potential of changes in NITs such as MRI-PDFF, ELF, or FAST Score for biopsy outcomes, however predictive models incorporating multiple top NIT candidates are under investigation to enhance model accuracy and refinement."

Biopsy • Non-invasive • P2 data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Direct effects of survodutide on liver endpoints beyond weight loss: insights from a phase 2 trial of the glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide in people with metabolic dysfunction-associated steatohepatitis and fibrosis (EASL 2025) - P2 | "The results suggest that MASH resolution induced by survodutide was broadly mediated by WL. However, liver endpoints related to improvement in inflammation and fibrosis were less so, suggesting the reduction in these endpoints can be attributed to a direct effect of survodutide on the liver, likely via direct glucagon effect beyond WL."

P2 data • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Gene expression of skeletal muscle is not differently regulated in weight-matched DIO mice treated with survodutide or semaglutide (ECO 2025) - No abstract available

Preclinical

Pharmacogenomic analysis of the GLP-1 receptor in a phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist, in adults with obesity (ECO 2025) - No abstract available

Biomarker • Clinical • Genomic analysis • Omic analysis • P2 data • Genetic Disorders • Obesity

The dual glucagon/GLP-1 receptor agonist survodutide improved cardiovascular risk biomarkers in adults with obesity in a phase 2 trial (ECO 2025) - No abstract available

Biomarker • Clinical • P2 data • Cardiovascular • Genetic Disorders • Obesity

A Study to Test Whether Survodutide Improves How the Body Uses Energy and Breaks Down Fat in People With Obesity (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Study in Women With Overweight or Obesity to Test Whether Different Doses of BI 456906 Influence the Amount of a Contraceptive in the Blood (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Survodutide Improves Heart Failure with Preserved Ejection Fraction and Dyslipidemia in a Diet-Induced Obese Hamster Model (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Preclinical • Metabolic Disorders • Obesity

Comparison of Pharmacological Therapies for Metabolic Dysfunction-Associated Steatohepatitis: Systematic Review and Network Meta-analysis (APASL 2025) - "For the co-primary endpoint of fibrosis improvement without MASH resolution, pegozafermin, cilofexor + firsocostat, survodutide, obeticholic acid, tirzepatide, and resmetirom were significantly better than placebo in improving ≥ 1 fibrosis stage without worsening MASH. Pegozafermin (SUCRA: 90.18), cilofexor plus firsocostat (SUCRA: 82.82), and cilofexor plus selonsertib (SUCRA: 79.62) were ranked the most effective interventions. For the co-primary endpoint of MASH resolution without worsening fibrosis, pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, and lanifibranor were significantly better than placebo... This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

East Asian Sub-Analysis of a Phase 2 Trial of the Glucagon and GLP-1 Receptor Dual Agonist Survodutide in People with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis (APASL 2025) - P2 | "Overall, survodutide was generally well tolerated and showed benefit compared with PBO in East Asian participants with MASH and fibrosis. Table and Figure:Figure 1.Changes in parameters after 48 weeks of treatment"

P2 data • Diabetes • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study in People With Overweight or Obesity to Test How BI 1820237, BI 456906, or a Combination of Both Affects Brain Activity (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. (PubMed, Peptides) - "Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)...New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The..."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Orthopedics • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT) (clinicaltrials.gov) - P3 | N=5549 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Nephrology • Obesity • Renal Disease

The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists. (PubMed, Expert Opin Investig Drugs) - "Our narrative review of English articles included four GLP-1RAs (subcutaneous semaglutide, liraglutide, dulaglutide, and efpeglenatide), a dual GLP-1/GIP agonist (tirzepatide), a dual GLP-1/glucagon receptor agonist (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes and landscape. Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes. Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Fibrosis • Gastroenterology • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Obstructive Sleep Apnea • Polycystic Ovary Syndrome • Renal Disease • Respiratory Diseases • Sleep Disorder • Type 2 Diabetes Mellitus

A Study to Test Whether Multiple Doses of BI 456906 Have an Effect on Cardiac Safety in People With Overweight or Obesity (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=80 ➔ 110

Enrollment change • Enrollment closed • Genetic Disorders • Obesity

A Study in Healthy People to Compare How 3 Different Formulations of Survodutide Are Taken up in the Body (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

Survodutide: Primary completion of P3 SYNCHRONIZE-1 trial (NCT06066515) for obesity in H2 2025 (Zealand Pharma) - Annual Report 2024: Primary completion of P3 SYNCHRONIZE-2 trial (NCT06066528) for obesity in H2 2025

Trial primary completion date • Obesity

Emerging pharmacotherapies for obesity: A systematic review. (PubMed, Pharmacol Rev) - "Oral semaglutide 50 mg is the only medication that has completed a phase 3 trial. There are 14 ongoing phase 3 trials on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, and TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide and survodutide), GLP-1/glucose-dependent insulinotropic polypeptide and glucagon RA (retatrutide), dapagliflozin, and the combination sibutramine/topiramate...This systematic review identifies the state and mechanism of action of emerging pharmacotherapies undergoing or having completed phase 2 and phase 3 clinical trials. The information provided herein furthers the understanding of obesity management, implying direct clinical implications and stimulating research initiatives."

Journal • Review • Genetic Disorders • Obesity

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis. (PubMed, Hepatology) - "This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT) (clinicaltrials.gov) - P3 | N=4935 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Apr 2026 ➔ Jul 2026

Trial completion date • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Nephrology • Obesity • Renal Disease