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

Review: Special Issue: Real-world evidence on the use of GLP1 receptor agonists: Emerging concepts in obesity management: focus on glucagon receptor agonist combinations. (PubMed, Drugs Context) - "Agents like mazdutide, pemvidutide, survodutide and retatrutide have demonstrated the ability to trigger significant weight loss in earlier phase trials, often surpassing the amount of weight loss obtained with existing therapies...Key considerations as these drugs move forward in development to eventual approval include cost, access and long-term safety. This article is part of the Real-world evidence on the use of GLP1 receptor agonists Special Issue: https://www.drugsincontext.com/special_issues/real-world-evidence-on-the-use-of-glp1-receptor-agonists."

HEOR • Journal • Real-world evidence • Review • Cardiovascular • Diabetes • Endocrine Disorders • 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

Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. (PubMed, Obesity (Silver Spring)) - "Retatrutide offers superior weight loss efficacy but with a higher AE risk. Dual agonists provide a favorable efficacy-safety balance. Personalized treatment selection based on patient characteristics is recommended."

Journal • Review • 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

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

Efficacy and Safety of Twincretin Survodutide, a Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist as an Anti-Obesity and Anti-Diabetes Medication: A Systematic Review and Meta-Analysis. (PubMed, Indian J Endocrinol Metab) - "Survodutide demonstrates impressive weight and glucose-lowering properties over short-term clinical use. The optimal dose for clinical use ranges from 2.4 to 4.8 mg/week."

Journal • Retrospective data • Review • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study in Healthy People to Compare How 2 Different Formulations of Survodutide Are Taken up in the Body (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, Curr Pharm Des) - "Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option...However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs."

Journal • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. (PubMed, J Clin Invest) - "Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FASN • FGF21 • PNPLA3

Analysis of glucose biomarkers in phase 1 and phase 2 studies of survodutide in people with type 2 diabetes or living with overweight/obesity (EASD 2025) - P1, P2 | "Survodutide treatment showed improvement in markers of insulin sensitivity, pancreatic islet cell function, and glucose biomarkers, in patients living with obesity/overweight and those with type 2 diabetes."

Biomarker • P1 data • P2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide. (PubMed, Mol Metab) - "Regression-based interaction analysis demonstrated that BI 1820237 increased the efficacy of survodutide by 265% at an ED50 of 11.7 nmol/kg over a range of dose combinations. Synergistic NPY2R and GCGR/GLP-1R agonism provides an attractive mode of action for clinically relevant weight loss in patients with obesity."

Journal • Genetic Disorders • Obesity

Dissecting food intake-dependent and independent effects of survodutide on transcriptome, lipidome and systemic insulin sensitivity (EASD 2025) - "Survodutide shows superior effects on improving insulin resistance, compared to PF. Both survodutide and PF increase systemic insulin sensitivity via improvements in BAT, muscle, and liver insulin responses. However, only survodutide leads to enhanced WAT insulin sensitivity."

Metabolic Disorders • Obesity • IR

Survodutide, a novel dual GLP-1 receptor/glucagon receptor agonist, improves kidney health in a mouse model of advanced diabetic kidney disease (EASD 2025) - "Survodutide markedly improved metabolic and renal outcomes in the db/db UNx-ReninAAV mouse model of advanced DKD, supporting further investigations into therapeutic options of survodutide in chronic kidney diseases."

Metastases • Preclinical • Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • KIM1

Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Proc (Bayl Univ Med Cent)) - "Survodutide effectively reduced relative body weight, absolute body weight, and hemoglobin A1c (P < 0.00001). The incidence of adverse events was comparable between the two groups, while gastrointestinal adverse events were higher in the survodutide group."

Journal • Retrospective data • Genetic Disorders • Obesity

Survodutide: a novel peptide for treatment of obesity and metabolic diseases. (PubMed, Proc (Bayl Univ Med Cent)) - No abstract available

Journal • Genetic Disorders • Metabolic Disorders • Obesity

Metabolic and Physiological Effects of Survodutide in Polygenic Type 2 Diabetic Mice (NZO/HILtJ) under Thermoneutral Conditions (ADA 2025) - "Overall, Survodutide treatment under thermoneutral conditions reduced body weight, fat mass, food intake, and blood glucose levels in NZO/HILtJ mice, while also lowering energy expenditure, emphasizing the role of environmental temperature in metabolic drug effects."

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

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) - "OPK-88006 treatment improved metabolic, biochemical and histopathological parameters of MASH, including hepatic transcriptomic profile, in the GAN DIO-MASH mouse model. Notably, OPK-88006 treatment improved NAFLD Activity Score superior to late-stage clinical candidates semaglutide and survodutide, introducing OPK-88006 as a promising treatment for MASH."

Biopsy • Late-breaking abstract • Preclinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • TIMP1

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

Survodutide Improves Heart Failure with Preserved Ejection Fraction and Dyslipidemia in a Diet-Induced Obese Hamster Model (ADA 2025) - "Survodutide significantly reduced body weight and demonstrated improvements in HFpEF and dyslipidemia in the DIO hamster model. These preclinical data emphasize the potential cardiovascular benefits of survodutide for the treatment of obesity and related comorbidities."

Preclinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • 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 | 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

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