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

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

Trial completion

Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis. (PubMed, J Clin Endocrinol Metab) - "GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • KRT18

Echosens and Boehringer Ingelheim Expand Long-Standing Collaboration to Accelerate Progress in MASH Diagnosis and Care (The Manila Times) - "As metabolic dysfunction-associated steatohepatitis (MASH) emerges as one of the most dangerous and underdiagnosed drivers of liver failure...Echosens, the leader in non-invasive liver diagnostics, and Boehringer Ingelheim, a global biopharmaceutical company, today announced an expansion of their long-standing partnership to change the trajectory of the disease by moving beyond clinical trials to focus on early detection, diagnosis, and access to care....By combining their diagnostic and therapeutic expertise, Echosens and Boehringer Ingelheim aim to help close persistent gaps in awareness, real-world evidence, and clinical adoption....FibroScan, Echosens' non-invasive liver assessment technology, has played a critical role in Boehringer Ingelheim's liver disease research and continues to support two ongoing Survodutide Phase III trials by screening and monitoring patients..."

Licensing / partnership • Metabolic Dysfunction-Associated Steatohepatitis

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Comparative Efficacy and Safety of Glucagon Receptor Agonists in Metabolic Outcomes: A Network Meta-Analysis of Randomized Controlled Trials (ENDO 2025) - "Retatrutide and survodutide demonstrate superior efficacy in weight loss and glycemic control among glucagon receptor agonists, though at the cost of higher adverse event-related discontinuation."

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

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Gene expression of skeletal muscle is not differently regulated in weight-matched DIO mice treated with survodutide or semaglutide (ECO 2025) - "Weight-matched dosing with survodutide or semaglutide led to comparable and significant bodyweight and lean mass loss in DIO mice, but with no differences in lean mass loss when comparing the two treatments. Importantly, RNA sequencing of the gastrocnemius and soleus muscles revealed no significant differently regulated genes between treatment groups. The data indicate that the glucagon component of survodutide does not differently impact skeletal muscle gene expression compared to semaglutide."

Preclinical • Genetic Disorders • Obesity

Presentation of OBA: a phase 2 clinical trial testing the drug candidate BIO101 (20E) to limit the loss of muscle mass and function induced by semaglutide in patients with obesity (ECO 2025) - P2 | "Introduction: Survodutide is a unimolecular dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist in phase 3 clinical trials for chronic weight management in people living with obesity and, separately, for treating people with metabolic dysfunction-associated steatohepatitis. In this pre-specified exploratory analysis of a phase 2 trial, treatment with the dual GCGR/GLP-1R agonist survodutide was associated with improvements in molecular markers of cardiometabolic health and cardiovascular risk in people living with obesity."

Clinical • P2 data • Atherosclerosis • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • CCL18 • CRP • ICAM1 • LEP

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) - P2 | "The GLP-1R variants investigated here were not associated with changes in survodutide efficacy in this phase 2 trial population."

Biomarker • Clinical • Genomic analysis • Omic analysis • P2 data • Diabetes • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

The dual glucagon/GLP-1 receptor agonist survodutide improved cardiovascular risk biomarkers in adults with obesity in a phase 2 trial (ECO 2025) - P2 | "In this pre-specified exploratory analysis of a phase 2 trial, treatment with the dual GCGR/GLP-1R agonist survodutide was associated with improvements in molecular markers of cardiometabolic health and cardiovascular risk in people living with obesity."

Biomarker • Clinical • P2 data • Atherosclerosis • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • CCL18 • CRP • ICAM1 • LEP

Analysis of non-invasive liver biomarkers in a phase II study of dual glucagon and GLP-1 receptor agonists Survodutid in people with metabolic dysfunction-associated steatohepatitis and fibrosis (DDG 2025) - P2 | "Background: We examined non-invasive liver biomarkers from a phase II study with survodutide, a new dual glucagon (GCGR) and Glucagon-Like (GLP-1) receptor agonists, for the treatment of a mash and fibrosis... Participants who received Survodutid showed significant improvements from the LFC (MRI-PDFF and CAP), the liver tire (rated), the liver enzymes and other markers of the fibrosis (eleven, pro-C3), which correlated with improvements in the histological end points."

Biomarker • Non-invasive • P2 data • Diabetes • Metabolic Disorders

A Study to Test How BI 456906 is Taken up in the Blood of People With and Without Kidney Problems (clinicaltrials.gov) - P1 | N=37 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Renal Disease

Superior Hepatoprotective Effects of OPK-88006, a Novel GLP-1/Glucagon Receptor Dual Agonist, to Semaglutide and Survodutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Biopsy • Late-breaking abstract • Preclinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

The Molecular Basis of Survodutide (BI456906) Glucagon/GLP-1 Receptor Dual Agonism (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Late-breaking abstract • Metabolic Disorders

Metabolic and Physiological Effects of Survodutide in Polygenic Type 2 Diabetic Mice (NZO/HILtJ) under Thermoneutral Conditions (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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

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

Upcoming events next 12 months (GlobeNewswire) - "In the first half of 2026, Zealand Pharma expects to report topline results from the Phase 2 ZUPREME-1 trial and complete the Phase 2 ZUPREME-2 trial with petrelintide...Zealand Pharma and Roche expect to initiate Phase 2 trials with petrelintide/CT-388 in the first half of 2026...In the second quarter of 2025, Zealand Pharma expects to announce topline results from Part 2 of the Phase 1b trial evaluating higher doses of dapiglutide over 28 weeks of treatment, with subsequent initiation of a Phase 2 trial expected in the second half of 2025. Zealand Pharma will present the results from Part 1 of the Phase 1b trial at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois in June 2025....Topline data from SYNCHRONIZE-1 and SYNCHRONIZE-2, the Phase 3 trials with survodutide in participants with overweight or obesity without and with type 2 diabetes, respectively, are expected in the first half of 2026."

Clinical data • New P2 trial • Trial status • Obesity • Type 2 Diabetes Mellitus

Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD. (PubMed, Aliment Pharmacol Ther) - "GLP-1 receptor agonists, alone or in combination with GIP and/or glucagon receptor agonists, represent promising, effective pharmacotherapies for the treatment of MASLD/MASH. Larger and longer-duration clinical trials are needed to further evaluate the efficacy and safety of GIP receptor and glucagon receptor agonism."

Journal • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

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

Enrollment closed

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

A Study in Chinese People With Overweight or Obesity to Test How Different Doses of Survodutide Are Taken up in the Body (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • 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) - No abstract available

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

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

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

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