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

Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed. (PubMed, J Clin Med) - "(5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent...Many novel agents-many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)-are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon. (PubMed, J Obes) - "Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label...Novel agents including CagriSema and higher dose oral semaglutide are advancing through clinical trials, while pivotal trial results for orforglipron, mazdutide, retatrutide, and survodutide are anticipated to further expand the therapeutic landscape...The convergence of pharmacological innovation, digital health strategies, and equitable care initiatives is expected to revolutionize obesity therapeutics in the coming decade. Priorities for future research include sustaining long-term weight loss, establishing disease-modifying potential in nonmetabolic disorders, and addressing health equity concerns to ensure broader global benefit."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Survodutide for the Treatment of Obesity: Baseline Characteristics of the SYNCHRONIZE Cardiovascular Outcomes Trial. (PubMed, JACC Heart Fail) - No abstract available

Journal • Cardiovascular • Genetic Disorders • Obesity

A Study in Healthy People to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

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

Trial completion

Zealand Pharma Announces Financial Results for the First Nine Months of 2025 (GlobeNewswire) - "Achieved key milestone in the petrelintide Phase 2 ZUPREME-1 trial in people with overweight and obesity, with the last participant completing the 28-week primary endpoint visit, paving the way for 42-week topline data in H1 2026; Approaching Phase 3 data in H1 2026 with survodutide, following last participant last visit in the 76-week SYNCHRONIZE trial in people with overweight and obesity without type 2 diabetes; Zealand Pharma is excited to outline a catalyst-rich 2026 at its upcoming Capital Markets Day on December 11, highlighting its ambition to become a generational biotech company driving the next wave of innovation in obesity."

Clinical data • Obesity • Type 2 Diabetes Mellitus

Survodutide for the Treatment of Obesity: Baseline characteristics of the SYNCHRONIZE Cardiovascular Outcomes Trial (AHA 2025) - "SYNCHRONIZE-CVOT enrolled people who were overweight or obese across a broad spectrum of CVD and CKD risk categories. SYNCHRONIZE-CVOT is the first randomized, placebo-controlled, phase 3 trial that will determine the CV safety of survodutide in people with overweight/obesity and increased CV risk."

Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Genetic Disorders • Heart Failure • Hypertension • Myocardial Infarction • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Survodutide, glucagon/GLP-1 receptor dual agonist. (GlobeNewswire) - "In October 2025, the last participant in the Phase 3 SYNCHRONIZE-1 trial in people with overweight and obesity without type 2 diabetes completed the 76-week primary endpoint visit. Baseline characteristics for SYNCHRONIZE-1 and SYNCHRONIZE-2 were presented at the Obesity Society Annual Meeting (ObesityWeek) in Atlanta, U.S., in November 2025."

Enrollment closed • Trial status • Obesity • Type 2 Diabetes Mellitus

Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes. (PubMed, Diabetes Obes Metab) - P3 | "SYNCHRONIZE-2 will determine the efficacy, safety and tolerability of survodutide for BW reduction in people with obesity and T2D, whose baseline characteristics suggest a representative, diverse cohort."

Journal • P3 data • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

Survodutide for Weight Reduction in Obesity and T2D: Baseline Data From SYNCHRONIZE™-2 Phase 3 Trial (OBESITY WEEK 2025) - P3 | "This dedicated phase 3 trial (SYNCHRONIZE-2) randomized and treated 752 participants and will determine the weight-lowering efficacy and safety of survodutide for people with obesity and T2D."

P3 data • Atherosclerosis • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus • CRP

Survodutide for Treatment of Obesity: Baseline Characteristics in the SYNCHRONIZE™-1 Phase 3 Trial (OBESITY WEEK 2025) - P3 | "SYNCHRONIZE-1 randomized and treated 725 people with obesity without T2D and will determine the efficacy, safety, and tolerability of survodutide in a large multinational clinical trial."

P3 data • Atherosclerosis • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Diabetic Nephropathy • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus • CRP

Survodutide Improved Cardiometabolic Parameters in People With Obesity, & Those With MASH & Fibrosis (OBESITY WEEK 2025) - P2 | "Survodutide in people living with obesity, and in people with MASH and fibrosis, was associated with clinically meaningful improvements in cardiometabolic parameters, with no unexpected safety concerns."

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

Eating Behavior Measured by the EB PRO Correlated with Weight Loss in a Phase 2 Trial of Survodutide (OBESITY WEEK 2025) - P2 | "In this clinical study, changes in self-reported eating behavior assessed by the EB PRO measure were associated with changes in bodyweight and BMI. This finding suggests that change in EB PRO score could serve as a surrogate marker or predictor of intentional weight reduction in people living with obesity or overweight."

P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1). (PubMed, Diabetes Obes Metab) - P3 | "SYNCHRONIZE-1 will determine the efficacy, safety, and tolerability of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for weight loss in a representative cohort of people with obesity without T2D."

Clinical • Journal • P3 data • Cardiovascular • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

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

A Study in Healthy People to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

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 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • 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

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

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 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