Xinermei (mazdutide) / Eli Lilly, Innovent Biologics - LARVOL DELTA

Mazdutide Demonstrates Significant Weight Loss and Metabolic Benefits in Phase 1b Clinical Trial in Chinese Adolescents with Obesity (PRNewswire) - "After 12 weeks of treatment, the 4 mg and 6 mg mazdutide groups achieved reductions in BMI from baseline of 8.78% and 10.99%, respectively, with corresponding body weight reductions of 7.72 kg and 8.65 kg. These results were significantly superior to those observed in the placebo group (BMI reduction: 1.73%; weight reduction: 1.42 kg; with nominal P values < 0.01). Furthermore, multiple metabolic parameters improved simultaneously."

P1 data • Obesity

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

A Study of IBI362 in Chinese Adolescents With Obesity or Overweight (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New P3 trial • Genetic Disorders • Obesity

Innovent Biologics, Inc….announces that the supplementary application for the 9 mg dosage of mazdutide, an innovative glucagon (GCG)/ glucagon-like peptide-1 (GLP-1) dual receptor agonist, for the long-term weight management in adults with moderate to severe obesity has been accepted for review by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). (PRNewswire) - "This application is based on the encouraging results from the Phase 3 registration clinical study GLORY-2 (NCT06164873) of mazdutide 9 mg in Chinese adults with moderate to severe obesity."

China filing • Obesity

GLP-1/GCG Dual Agonist in Type 2 Diabetes With Early Dementia (LIGHT-COG Study) (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Phase classification: P4 ➔ P3 | Not yet recruiting ➔ Recruiting

Enrollment open • Phase classification • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

GLP-1/glucagon dual agonist reduces weight across three dosing regimens in obesity (Healio) - "At 32 weeks, the reduction in body weight with mazdutide was 7.3% with a 6 mg dose, 15.6% with the 10 mg dose and 18.1% with the 16 mg dose vs. a 0.9% weight reduction with placebo....At 48 weeks, 52% of the 16 mg mazdutide group and 49% of the 10 mg group lost at least 20% of their body weight compared with 3% of the placebo group...At 48 weeks, waist circumference decreased by 11 cm in the 6 mg mazdutide group, 16.7 cm in the 10 mg group and 16.6 cm with the 16 mg dose vs. a 1.2 cm reduction with placebo....All three mazdutide groups had significant decreases in HbA1c, fasting glucose and fasting insulin at 48 weeks compared with placebo."

P2 data • Obesity

Innovent Biologics…announces that the Phase 3 clinical trial of mazdutide, a first-in-class dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese adults with obesity (GLORY-2) met the primary endpoints and all key secondary endpoints (PRNewswire) - "The study enrolled 462 participants....During the treatment period, participants in the mazdutide group exhibited continuous weight loss, with no plateau observed in Week 60. At Week 60, the mazdutide 9 mg group achieved a mean weight reduction of 18.55%, compared to 3.02% in the placebo group. 44.0% of participants in the mazdutide 9 mg group achieved a weight reduction of 20% or more, versus 2.6% in the placebo group (P"

P3 data • Obesity

Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial. (PubMed, Contemp Clin Trials) - "DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026."

Journal • P3 data • Diabetes • Genetic Disorders • Gout • Hepatology • Inflammatory Arthritis • Metabolic Disorders • Obesity • Rheumatology • Type 2 Diabetes Mellitus

Innovent plans to submit the new drug application (NDA) of mazdutide 9 mg for weight management to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in the near term (PRNewswire)

China filing • Obesity

Mazdutide Inhibits p-ASK1 and SLC7A11-GPX4 Ferroptosis Axis to Improve Rat Uric Acid Nephropathy (OBESITY WEEK 2025) - "Eighty male SD rats were randomized into eight groups (n=10): CON (blank control), HFD (high-fat diet), UN (uric acid nephropathy), Mazdutide (0.025/0.05/0.075 mg·kg⁻¹), semaglutide (GLP-1RA), and allopurinol (25 mg·kg⁻¹). 1. Subcutaneous injection of Mazdutide every 3 days can improve uric acid nephropathy in SD rats.2. Administration of Mazdutide to HK-2 cells can improve cell viability reduced by uric acid administration and reduce cell apoptosis.3."

Preclinical • Fibrosis • Immunology • Renal Disease • ACSL4 • GPX4 • SLC7A11 • TGFB1

Mazdutide, A Dual GCGR/GLP-1R Agonist, Reduces Body Weight and Relieves Liver Lipid Deposition (OBESITY WEEK 2025) - "In HFD-fed mice, mazdutide demonstrated more effective weight loss and lipid reduction than other gut hormone-based therapies. By modulating lipid metabolism, mazdutide alleviated hepatic steatosis and fibrosis, demonstrating its potential as a novel therapeutic strategy for MASH."

Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Mazdutide Lowers Uric Acid via GCGR-Dependent Hepatic Metabolic Reprogramming (OBESITY WEEK 2025) - "Single-nucleus RNA sequencing (snRNA-seq) examined transcriptional changes in hepatocyte subpopulations.In vitro, human hepatocyte THLE-2 cells were cultured under hyperuricemic conditions and treated with Mazdutide, Semaglutide, or Allopurinol. Mazdutide effectively lowers serum uric acid by reprogramming hepatic metabolism toward enhanced lipid utilization, reduced purine synthesis, and improved oxidative stress through GCGR-dependent mechanisms. Unlike Semaglutide, Mazdutide exhibits robust urate-lowering activity both in vivo and in vitro, highlighting its therapeutic potential for hyperuricemia and related metabolic disorders.These findings suggest that Mazdutide may offer therapeutic benefits for patients with hyperuricemia, particularly those with obesity-related metabolic disorders."

Genetic Disorders • Metabolic Disorders • Obesity

Mazdutide (LY3305677) in Participants With Obesity or Overweight: A Phase 2 Dose-Finding Study (OBESITY WEEK 2025) - P2 | "The results of this phase 2 study will provide evidence for the efficacy and safety of mazdutide, similar to other molecules in this class, as a once-weekly injection to reduce excess body weight and maintain weight reduction in adult participants with obesity or overweight."

P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Mazdutide, GLP-1R/GCGR Co-Agonist, Achieves Superior Weight Loss by Regulating Energy Homeostasis (OBESITY WEEK 2025) - "Mazdutide demonstrates a unique advantage in regulating energy metabolism through its dual receptor agonism. Its weight-loss mechanism involves the coordinated activation of energy metabolism networks across multiple organs, offering a new therapeutic strategy for metabolic diseases."

Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Comparative Efficacy of Glucagon-Like Peptide-1 Receptor Agonists and Co-Agonists for Weight Loss Among Patients Without Diabetes: A Network Meta-Analysis (AHA 2025) - "BACKGROUND: Multiple glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer dual/triple co-agonists promote weight loss in adults without diabetes, yet comparative efficacy across agents remains uncertain.AIM: To compare and rank the efficacy of GLP-1 RAs and co-agonists for weight loss using network meta-analysis (NMA). We searched MEDLINE, EMBASE and Cochrane CENTRAL from inception to May 2025 for randomized controlled trials (RCTs) enrolling adults with overweight/obesity without diabetes...At 6 months, all agents significantly reduced weight versus placebo; retatrutide ranked highest (mean difference [MD]: -15.8%, 95% confidence interval [CI] -17.6 to -14.1; SUCRA 1.00), followed by mazdutide (MD: -12.3%, 95% CI -14.1 to -10.5; SUCRA 0.89) and orforglipron (MD: -10.6%, 95% CI -12.8 to -8.4; SUCRA 0.75)... Among adults without diabetes, dual- and triple-agonists, particularly tirzepatide and retatrutide, achieve the greatest weight reductions, while..."

Retrospective data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

SMART: Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Superiority Trial (ChiCTR) - P4 | N=256 | Not yet recruiting | Sponsor: Beijing Friendship Hospital ,Capital Medical University; Beijing Friendship Hospital ,Capital Medical University

Head-to-Head • New P4 trial • Gastrointestinal Disorder • Genetic Disorders • Obesity

Innovent’s Mazdutide Shows Superiority in Glycemic Control with Weight Loss over Semaglutide in a Head-to-head Phase 3 Clinical Trial DREAMS-3 (PRNewswire) - "...Phase 3 clinical trial DREAMS-3...has met its primary endpoint. The results demonstrated that, in Chinese patients with type 2 diabetes (T2D) and obesity, mazdutide showed superior efficacy to semaglutide on the primary endpoint-the proportion of participants achieving HbA1c < 7.0% and ≥10% body weight reduction from baseline at week 32 (48.0 vs. 21.0%, p<0.0001). In addition, at week 32, the mean change in HbA1c from baseline was −2.03% in the mazdutide group and −1.84% in semaglutide group, respectively, and the mean percentage weight reduction from baseline was 10.29% in the mazdutide group and 6.00% in the semaglutide group, respectively (both p<0.05)."

P3 data • Obesity • Type 2 Diabetes Mellitus

A Master Protocol Study (LY900038) of Multiple Intervention-Specific-Appendices (ISAs) in Adult Participants With Obesity or Overweight (clinicaltrials.gov) - P2 | N=1217 | Recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Sep 2026 ➔ Jun 2026

Trial primary completion date • 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

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

Case Report: Efficacy and safety of dose-escalated Mazdutide, a GLP-1/GCGR dual agonist, in an adolescent with obesity, type 2 diabetes, and hyperuricemia. (PubMed, Front Endocrinol (Lausanne)) - "The patient underwent a dose-escalation regimen of Mazdutide (2 mg → 4 mg → 6 mg, administered subcutaneously once weekly) in combination with metformin and insulin to evaluate therapeutic efficacy and safety outcomes. It improved glycemic control, reduced weight and uric acid, reversed steatosis, and modulated lipid profiles. These findings support its potential as a comprehensive treatment for adolescent metabolic disorders."

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

Mazdutide: First Approval. (PubMed, Drugs) - "Additionally, mazdutide is under clinical evaluation for use in the treatment of metabolic dysfunction-associated fatty liver disease, obstructive sleep apnoea and alcohol use disorder. This article summarises the milestones in the development of mazdutide leading to this first approval for long-term body weight management in adults with obesity or overweight."

Journal • Addiction (Opioid and Alcohol) • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

Innovent Announces Mazdutide Received Approval from China's NMPA for Glycemic Control in Adults with Type 2 Diabetes (PRNewswire) - "The approval was based on two Phase 3 clinical trials (DREAMS-1 [NCT05628311] and DREAMS-2 [NCT05606913]), which evaluated the efficacy and safety of mazdutide as monotherapy and in combination with oral antidiabetic drugs, respectively, in Chinese participants with T2D."

China approval • Type 2 Diabetes Mellitus

This is a Study to Evaluate the Pharmacokinetics and Safety of IBI362 in Chinese Adolescents With Obesity (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Innovent’s weight-loss drug highlights China challenge for Novo, Lilly (Reuters) - "Innovent Biologics'...newly launched weight-loss drug is making inroads in its home market of China, ramping up competition with its Western rivals as it pursues a marketing strategy that is gaining traction. Xinermei, launched in July, is the third once-weekly injectable GLP-1 weight management therapy available in China..."

Launch non-US • Obesity