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

Pathogenesis-Informed Phenotype-Guided Therapy for MASH: A Three-Axis Translational Framework Within the MASLD Spectrum. (PubMed, Biomedicines) - "Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive inflammatory and fibrotic subtype of metabolic dysfunction-associated steatotic liver disease (MASLD), and its treatment landscape is rapidly moving from nonspecific liver fat reduction towards mechanism-based drug positioning. Since 2024, resmetirom and semaglutide have received U.S. Food and Drug Administration accelerated approval for non-cirrhotic MASH with moderate-to-advanced fibrosis, while tirzepatide, survodutide, and fibroblast growth factor 21 analogues have shown biopsy-based phase 2 or 2b efficacy signals...In particular, weight-centred treatment should not be assumed to apply to all patients, including normal-weight or lean MASH. Overall, future MASH therapy will likely depend on matching drug mechanisms, fibrosis stage, cardiometabolic phenotype, and treatment goals."

Journal • Review • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Comparative Efficacy and Safety of FGF21 Analogues in MASH: Which Agents Are Advancing and Why? (ACG 2026) - "Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of progressive liver fibrosis and cirrhosis... A structured literature review of PubMed/MEDLINE was conducted through April 2026 using keywords and MeSH terms including âMASH,â âNASH,â âfibroblast growth factor 21,â âFGF21 analogues,â âefruxifermin,â âpegozafermin,â âefimosfermin,â âpegbelfermin,â âresmetirom,â âsemaglutide,â âtirzepatide,â âsurvodutide,â âlanifibranor,â and âclinical trial.â Included studies were randomized controlled trials in biopsy-confirmed MASH or MASLD reporting histologic data...Trials of pegbelfermin and MK-3655 did not meet primary endpoints... Twelve trials (N=3,640) were included. Among FGF21 analogues, efruxifermin 50 mg showed the greatest response, with fibrosis improvement up to 75% and MASH resolution up to 62%..."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Comparative Efficacy and Safety of Newly FDA-Approved Oral Orforglipron Versus Injectable GLP-1, Dual-, and Triple-Agonist Therapies: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the global gastrointestinal disease burden. 24 RCT's comprising 14,240 patients were included, including 8,412 females (59.1%) and 5,828 males (40.9%). Treatment arms included oral orforglipron (n=3,120), semaglutide (n=3,450), tirzepatide (n=2,880), liraglutide (n=1,850), retatrutide (n=1,680), and survodutide (n=1,260). Mean baseline BMI ranged from 36.1â38.1 kg/m² and HbA1c from 7.9â8.3%."

Retrospective data • Review • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Efficacy and Safety of Incretin-Based Therapies in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Trials (ACG 2026) - "Agents included liraglutide, semaglutide, dulaglutide, tirzepatide, pemvidutide, survodutide, efinopegdutide, and retatrutide... Sixteen MASLD/MASH randomized trials were included. Five biopsy-based trials contributed to MASH/NASH resolution without worsening fibrosis (n=1,226); incretin-based therapy increased resolution versus control (RR 2.80, 95% CI 1.60â4.90; p=0.007; I²=66.6%). Four biopsy-based trials reported fibrosis improvement without MASH worsening (n=1,181), favoring incretin-based therapy (RR 1.52, 95% CI 1.13â2.05; p=0.021; I²=0%)."

Retrospective data • Review • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Comparative Effectiveness of Survodutide, Tirzepatide, and Semaglutide in MASH: A Comprehensive Network Meta-Analysis of 1,573 Patients (ACG 2026) - "Introduction: Metabolic-associated steatohepatitis (MASH) lacks approved therapies, and emerging incretin-based agents such as survodutide, tirzepatide, and semaglutide have shown promising histologic and metabolic benefits in recent randomized trials. Five randomized controlled trials involving 1,573 patients with biopsy-confirmed MASH (F1BâF3 fibrosis) were included, comprising 219 patients receiving survodutide (74 placebo), 142 receiving tirzepatide (48 placebo), and 616 receiving semaglutide (346 placebo). Across trials, 723 (45.9%) were male and 850 (54.1%) female, with mean ages ranging from 51 to 56 years. All active agents significantly improved MASH resolution compared with placebo."

HEOR • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Comparative Efficacy and Safety of Incretin-Based Therapies, FGF21 Analogs, and Pan-PPAR Agonists for MASH: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Metabolic dysfunctionâassociated steatohepatitis (MASH) is an increasing global health burden with limited approved therapies... A total of 14 RCT's comprising 8,462 patients were included, with 53.1% males and 46.9% females. Patients received semaglutide (n=1,642), tirzepatide (n=1,128), survodutide (n=612), retatrutide (n=318), efruxifermin (n=742), pegozafermin (n=512), lanifibranor (n=247), resmetirom (n=2,955), or placebo/standard therapy (n=306). Baseline age, BMI, diabetes prevalence, ALT, and fibrosis stages were comparable."

Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

New Therapeutic Approaches for MASH: Mechanisms and Clinical Promise (PubMed, Z Gastroenterol) - "The thyroid hormone receptor-β agonist resmetirom became the first drug approved in Germany in 2025 for non-cirrhotic MASH with moderate to advanced fibrosis...Beyond GLP-1 analogs, which act indirectly through metabolic pathways, several liver fibrosis-specific therapies are emerging, including FGF-21 analogs and dual incretin receptor agonists (e.g. survodutide) that directly affect hepatocytes via glucagon receptor signaling...This review summarizes recent advances and future perspectives in the pharmacological treatment of MASH. The combination of metabolic and liver-targeted therapies offers substantial promise for personalized medicine."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • FGF21

MASLD: Established Knowledge and Emerging Directions - Guideline Updates. (PubMed, Z Gastroenterol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health challenge, largely driven by the increasing prevalence of obesity and type 2 diabetes mellitus...Promising clinical data have been reported for resmetirom, semaglutide, tirzepatide, survodutide, lanifibranor, and fibroblast growth factor-21 analogues including efruxifermin, pegozafermin, and efimosfermin.This review summarises current and emerging diagnostic and therapeutic strategies and provides practical guidance for clinical management. In addition, a structured treatment algorithm for non-cirrhotic MASLD (F0-F3), restricted to therapies currently available in Europe and stratified according to diabetes status and fibrosis stage, is proposed as an evidence-based tool for routine clinical practice."

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

A frequentist network meta-analysis of bariatric surgery versus next-generation injectable and oral incretins for cardiometabolic disease (EASD 2026) - "Materials and A frequentist network meta-analysis was conducted synthesizing data from surgical RCTs (Roux-en-Y Gastric Bypass [RYGB], Sleeve Gastrectomy [SG]) and Phase 2/3 trials of advanced pharmacotherapies (tirzepatide, retatrutide, survodutide, CagriSema, and orforglipron)... When pooling estimates across broad metabolic populations, next-generation incretins successfully bridge the placebo- adjusted efficacy gap to bariatric surgery. The most potent injectable multi-agonists match the absolute mass offloading of sleeve gastrectomy, while accessible daily oral small molecules rival legacy surgical banding."

Bariatric surgery • Retrospective data • Surgery • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Pharmacological management of obesity: Current landscape and emerging therapies. (PubMed, Indian J Pharmacol) - "Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy...It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries."

Journal • Review • Cardiovascular • CNS Disorders • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Psychiatry • Type 2 Diabetes Mellitus

Defining the efficacy and tolerability ceiling of pure incretin therapies in steatotic liver disease: a network meta-analysis of phase 2 and 3 trials (EASD 2026) - "(1) Liver Fat Clearance (MRI-PDFF): The tri-agonist retatrutide achieved the highest efficacy hierarchy (SUCRA 98%), yielding a -82.4% relative reduction in hepatic steatosis. GLP-1/glucagon dual-agonists (mazdutide, efinopegdutide) consistently outperformed both GLP-1/GIP agents and pure GLP-1 mono-agonists...While earlier dual-agonists (survodutide, cotadutide) exhibited high adverse event-related discontinuation rates (15.2-20.0%), next-generation agents (mazdutide, pemvidutide) maintained placebo-like tolerability (<1.0% discontinuation) alongside profound hepatic fat clearance. Multi-receptor incretin agonism yields a stepwise, dose-and-receptor dependent superiority in clearing hepatic steatosis compared to pure GLP-1 therapy. While the addition of glucagon drives unparalleled fat clearance, optimizing the tolerability profile remains the defining factor for the clinical viability of next-generation incretins."

P2 data • Retrospective data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Efficacy and Safety of Dual and Triple Glucagon-Like Peptide-1-Based Polyagonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-Analysis. (PubMed, Cureus) - "The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%)...However, gastrointestinal intolerance, pharmacological heterogeneity, the small number of trials, and limited follow-up warrant cautious interpretation. Larger phase 3 trials are needed to clarify drug-specific efficacy, long-term safety, and effects on liver-related and cardiovascular outcomes."

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

A Study to Compare How 2 Different Formulations of Survodutide Are Taken up in the Body When Given by Injection in Healthy Men and Women With and Without Overweight or Obesity (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Study in People With Overweight or Obesity to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

The Dual GCGR/GLP-1R Agonist Survodutide Demonstrates Multiple Cardiometabolic Benefits in a Free Choice Diet-Induced Obese Hamster Model (AHA 2026) - "Abstract is embargoed at this time."

Preclinical • Obesity

Efficacy and safety of survodutide, a novel GCG/GLP-1 receptor dual agonist, for treatment of people with obesity and T2D: primary data from the SYNCHRONIZETM-2 trial (EASD 2026) - No abstract available

Clinical • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • GCG

S36: Glucagon receptor/GLP-1 receptor dual agonism in people with obesity and type 2 diabetes: insights from the SYNCHRONIZE Phase 3 studies of survodutide (EASD 2026) - No abstract available

P3 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Survodutide enhances glutathione synthesis via the transsulfuration pathway in the liver (EASD 2026) - "Survo shows superior effects on improving weight loss and systemic and adipose insulin resistance, compared to PF. Comprehensive omics analyses show that Survo early on leads to higher GSH levels via enhanced transsulfuration pathway in the liver. Collectively, these findings point to a novel effect of Survo in uniquely enhancing the endogenous antioxidant capacity, which is likely driven by the hepatic GCGR agonism-induced enhanced metabolic state."

Metabolic Disorders • Obesity

Author Correction: Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial. (PubMed, Nat Med) - No abstract available

Clinical • P3 data • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

A Study to Test Whether Survodutide Helps People With Type 2 Diabetes Control Their Blood Sugar (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Development and validation of a multiplexed LC-HRMS method for nine GLP-1 receptor agonists and its pharmaceutical application. (PubMed, J Chromatogr A) - "A rapid, sensitive, and selective multiplexed liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed and validated for the identification and quantitation of nine structurally diverse peptide-based glucagon-like peptide-1 receptor agonists (GLP-1 RAs): bofanglutide, ecnoglutide, exenatide, liraglutide, mazdutide, retatrutide, semaglutide, survodutide, and tirzepatide. It was successfully applied to marketed formulations of liraglutide, semaglutide, and tirzepatide using a simple dilute-and-shoot procedure, yielding mean recoveries of 113.7-118.4%. This LC-HRMS method offers superior selectivity and flexibility for analysing current and next-generation GLP-1 RAs."

Journal

A Study to Compare How 2 Different Formulations of Survodutide Are Taken up in the Body When Given by Injection in Healthy Men and Women With and Without Overweight or Obesity (clinicaltrials.gov) - P1 | N=44 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial • Genetic Disorders • Obesity

Results from the Phase 3 SYNCHRONIZE-2 trial will be presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD). Results from the SYNCHRONISE-CVOT trial are expected to be reported and presented later in the year. (GlobeNewswire)

P3 data • Cardiovascular • Obesity • Type 2 Diabetes Mellitus

Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline Characteristics (SYNCHRONIZE™-CN). (PubMed, Diabetes Ther) - P3 | "This trial was designed to provide a robust evaluation of efficacy and safety of survodutide for the treatment of obesity or overweight in Chinese adults."

Clinical • Journal • P3 data • Cardiovascular • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • Type 2 Diabetes Mellitus

Anti-Obesity Medications in Longevity and Aesthetic Medicine. (PubMed, J Clin Med) - "Anti-obesity medications (AOMs), led by the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have produced substantial weight reduction and growing signals of benefit that extend well beyond adiposity. Newer multi-receptor agents act with greater metabolic specificity: glucagon-containing agents such as survodutide and the triple agonist retatrutide preferentially reduce visceral and hepatic fat (liver-fat reductions of roughly 60-80% in places), a quality of weight loss arguably more relevant to healthspan than its quantity. Concurrently, rapid large-magnitude weight loss drives soft-tissue and appearance changes colloquially termed "Ozempic face" and "Ozempic body", alongside accelerated skin laxity and loss of lean mass, the latter tempered by data showing lean-loss proportions comparable to established agents."

Journal • Review • Aesthetic Medicine • Cardiovascular • Genetic Disorders • Hepatology • Obesity