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

Incretin-Based Therapies in MASH: A Meta-Analysis of Hepatic and Metabolic Outcomes (ACG 2025) - "Incretin-based therapies significantly reduced liver fat in MASH patients. Triple agonist retatrutide achieved the greatest reduction (up to 83%), followed by dual GLP-1/glucagon agonists (pemvidutide: 64%, survodutide: 60%) and GLP-1/GIP agonist tirzepatide (47%). GLP-1 monotherapy (semaglutide) also reduced liver fat (39%) and improved liver enzymes."

Retrospective data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

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 (ACG 2025) - P2 | "Whole blood samples were available from 344 participants; of these, 337 samples were available for analysis following DNA extraction and quality checks. Genotyping analysis revealed no statistically significant treatment effect heterogeneity between these genetic variants and the observed changes in bodyweight (rs6923761 p=0.44; rs10305420 p=0.69; rs2268640 p=0.48) (Figure), waist circumference (rs6923761 p=0.89; rs10305420 p=0.38; rs2268640 p=0.44), and selected protein biomarkers; blood HbA1c (rs6923761 p=0.94; rs10305420 p=0.38; rs2268640 p=0.61); fasting plasma glucagon (rs6923761 p=0.85; rs10305420 p=0.95; rs2268640 p=0.40), and fasting plasma glucose (rs6923761 p=0.82; rs10305420 p=0.63; rs2268640 p=0.19); and fasting serum insulin (rs6923761 p=0.32; rs10305420 p=0.97; rs2268640 p=0.55). The GLP-1R variants investigated here were not associated with changes in survodutide efficacy in this phase 2 trial population.Encore: Originally presented at ECO 2025Figure:..."

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

Meta-Analysis of Survodutide: Impact on Satiety, Appetite, Gastrointestinal Adverse Effects, and Drug Discontinuation (ACG 2025) - "A total of 1,225 patients from 5 RCTs were included, with 978 patients receiving Survodutide in different doses, and 247 in the control group. Survodutide-treated patients showed higher odds of decreased appetite (OR = 3.39, p = 0.0004, 95% CI: 0.54–1.90, I² = 19.6%). The odds of early satiety were higher but not statistically significant (OR = 3.37, p = 0.065, 95% CI: -0.08 to 2.51, I² = 0%)."

Adverse events • Retrospective data • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Histological efficacy of anti-diabetic agents in MASH and the mediating role of weight loss: A network meta-analysis. (PubMed, Diabetes Obes Metab) - "SGLT2 inhibitor and incretin-based agents improved fibrosis in MASH, with weight loss being a significant mediator. Targeting multiple incretin pathways, especially involving glucagon receptors, may offer greater MASH resolution. Dose-dependent effects were more prominent for MASH resolution than fibrosis improvement, indicating potential weight-loss-independent anti-fibrotic pathways."

Journal • Retrospective data • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

SURVODUTIDE IMPROVED LIVER HISTOLOGY IN PEOPLE WITH MASH AND MODERATE-TO-SEVERE FIBROSIS REGARDLESS OF AGE, SEX, ETHNICITY, OR TYPE 2 DIABETES: SUBGROUP ANALYSIS OF A RANDOMIZED PHASE 2 TRIAL (AASLD 2025) - P2 | "Survodutide reduced MASH, fibrosis, and LFC across participant subgroups in this phase 2 trial, suggesting consistent benefits of this GCGR/GLP-1R dual agonist in different patient populations. There was no difference in MASH resolution based on age, sex, ethnicity, or T2D—and no difference in fibrosis improvement based on age, sex, or ethnicity, although response rate was possibly lower in those with T2D."

Clinical • P2 data • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • 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 (AASLD 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 • Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • TIMP1

IMPROVEMENTS IN NON-INVASIVE BIOMARKERS AND BIOPSY RESPONSES WITH THE GLUCAGON RECEPTOR/GLUCAGON-LIKE PEPTIDE-1 RECEPTOR DUAL AGONIST SURVODUTIDE: CONCORDANCE ANALYSIS FROM A PHASE 2 TRIAL IN PEOPLE WITH METABOLIC DYSFUNCTION–ASSOCIATED STEATOHEPATITIS AND FIBROSIS (AASLD 2025) - "The concordance of multiple NITs and biopsy results provides clear evidence of a robust effect from survodutide (over and above the PBO response) in the improvement of fibrosis (reduction of ELF™ and LSM) and resolving steatohepatitis (reduction of LFC and ALT) across all doses after 48 weeks."

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

DIRECT EFFECTS OF GLP-1/GLUCAGON DUAL AGONIST SURVODUTIDE ON HEPATIC STELLATE CELLS AND LIVER CANCER CELL LINES (AASLD 2025) - "Survodutide directly suppressed the proliferation of human HCC cells under lipotoxic stress. Survodutide also inhibited activated human HSC proliferation under profibrotic conditions, without affecting fibrogenic gene expression. These findings suggest a potential direct anti-tumor and anti-fibrotic effect of survodutide in the context of MASH progression."

Preclinical • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor • ACTA2 • COL1A1 • TGFB1 • TIMP1

Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity. (PubMed, Endocr Rev) - "Maridebart cafraglutide, combining GLP-1R agonism with GIPR antagonism, exemplifies this innovative approach. Glucagon co-agonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multi-receptor agonists..."

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

Survodutide for the Treatment of Obesity: Baseline characteristics of the SYNCHRONIZE Cardiovascular Outcomes Trial (AHA 2025) - "Available on Saturday, November 08, 2025 at 02:30pm CDT."

Cardiovascular • Genetic Disorders • Obesity

Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction-associated steatotic liver disease, and other cardio-kidney-metabolic conditions. (PubMed, Diabetes Obes Metab) - "In early clinical trials, several GCGR-based multi-agonists (mazdutide, survodutide [being developed by the sponsor of this review], retatrutide) demonstrated substantial efficacy for eliciting weight loss in people with obesity while improving liver health in those with MASLD. Thus, there is great interest in the ongoing phase 3 clinical trials of these compounds. As data for their safety and efficacy emerge, glucagon's role in energy regulation and lipid metabolism will become clearer, along with warranting a potential new therapeutic option for obesity and MASLD."

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

A Study to Test How BI 456906 is Taken up in the Blood of People With and Without Kidney Problems (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Renal Disease

A Study to Test How BI 456906 is Taken up in the Blood of People With and Without Kidney Problems (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Renal Disease

ARTIST-CKD: Albuminuria Reduction Study With Survodutide Treatment in Kidney Disease (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University Medical Center Groningen

New P2 trial • Chronic Kidney Disease • Nephrology • Renal Disease • CST3

Survodutide: A Dual GLP-1/Glucagon Agonist Reshaping Cardiometabolic Care. (PubMed, Cardiol Rev) - "Survodutide has the potential to reshape cardiometabolic care by addressing multiple converging pathways that drive cardiovascular disease. Confirmation of its safety and efficacy in outcomes trials could establish dual agonism as a cornerstone therapeutic strategy for patients with obesity, type 2 diabetes, MASH, and cardiorenal disease."

Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Genetic Disorders • Heart Failure • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Type 2 Diabetes Mellitus

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

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

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

Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis. (PubMed, Diabetes Obes Metab) - "Survodutide significantly reduced HbA1c, body weight, and waist circumference. A greater reduction in HbA1c was specifically associated with a higher total weekly dose (>2.4 mg), while more pronounced effects on body weight and waist circumference were observed with both higher doses and longer treatment durations (>16 weeks). However, it is crucial to highlight the significant increase in gastrointestinal AEs and the associated risk of treatment discontinuation. Further large-scale, multicentre, long-term, and high-quality RCTs are necessary to validate these results in diverse populations."

Journal • Retrospective data

A Study in People With Obesity to Test the Effects of BI 456906 Compared With Semaglutide on Glucagon Receptor Activity in the Liver (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Mar 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

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

Enrollment closed

Weight management treatment in obesity. (PubMed, Med Clin (Barc)) - "Glucagon-like peptide-1 (GLP-1) receptor agonists (RA), used as weekly injectable monotherapy or daily oral (semaglutide), achieve weight loss of 15-17%, with a good safety profile...In this same range of weight loss, it is expected that it can be achieved with the combination of Cagrisema (cagrilintide 2.4mg plus semaglutide 2.4mg), combinations of GLP-1 RAs - glucagon agonists or with the triple combination of GLP-1 RAs-GIP-Glucagon (Retatrutide). In this review, we will examine the efficacy and safety of the drugs marketed and others under ongoing clinical trials for the treatment of persons with obesity, as well as the main challenges faced by both healthcare professionals and patients in maintaining long-term treatment."

Journal • Review • 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 | Trial completion date: Jun 2026 ➔ Jan 2027 | Trial primary completion date: May 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism. (PubMed, JACC Basic Transl Sci) - "H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Obesity • SQOR

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