mazdutide (LY3305677) / Eli Lilly, Innovent Biologics - 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

A Study of IBI362 in Participants With Metabolic Dysfunction-Associated Steatohepatitis (MASH) (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight (clinicaltrials.gov) - P2 | N=179 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

GLP-1/GCG Dual Agonist in Type 2 Diabetes With Cognitive Dysfunction (LIGHT-COG Study) (clinicaltrials.gov) - P4 | N=432 | Not yet recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

New P4 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Metabolic Disorders • 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: Jun 2026 ➔ Sep 2026

Trial primary completion date • Genetic Disorders • Obesity

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

Tolerance and Pharmacokinetic/Pharmacokinetic Study of IBI362 15mg in Patients With Moderate to Severe Obesity (clinicaltrials.gov) - P1/2 | N=98 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

Synergy in Action: Novel Combination Strategies for DKD: New Horizons in DKD: Emerging Diagnostic and Therapeutic Approaches (KSN 2025) - "The lecture will then explore the revolutionary potential of multi-receptor agonists—including dual GLP-1/GIP agonists (tirzepatide), triple GLP-1/GIP/glucagon agonists (retatrutide, mazdutide), and novel combinations like amycretin and cagrisema—which may fundamentally "remodel" the metabolic phenotype of DKD...Special consideration will be given to Asian populations, where lower BMI but high metabolic risk may offer unique opportunities for these novel combinations. The lecture will conclude with a vision for precision medicine in DKD."

Chronic Kidney Disease • Diabetic Nephropathy • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease

GLORY-OSA: A Study of IBI362 in Chinese Subjects With Obstructive Sleep Apnea and BMI≥28 kg/m2 (clinicaltrials.gov) - P3 | N=260 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

CN NMPA Approves Innovent Biologics’ GLP-1 Weight Loss Drug for Marketing (iis.aastocks.com) - "China's National Medical Products Administration (NMPA) has recently approved the market launch of Innovent Biologics (Suzhou)'s Class 1 innovative drug Mazdutide injection. This drug is a dual receptor agonist for glucagon and glucagon-like peptide-1 (GLP-1), indicated for long-term weight management in adult patients, in conjunction with dietary control and increased physical activity, who also have at least one weight-related comorbidity (such as hyperglycemia, hypertension, dyslipidemia, fatty liver, or obstructive sleep apnea syndrome)."

China approval • Obesity

Mazdutide vs. Placebo as Monotherapy in Patients with Type 2 Diabetes (DREAMS-1) (ADA 2025) - "In Chinese patients with T2D, MAZ as monotherapy demonstrated robust and clinical meaningful HbA1c and body weight reduction."

Clinical • Monotherapy • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Effect of Mazdutide on MASH Fibrosis—Targeting the Liver–Gut Axis and Microbiome (ADA 2025) - "In conclusion, Mazdutide alleviates hepatic fibrosis in MASH mice and regulates lipid metabolism as well as the gut microbiota, which may contribute to providing a novel therapeutic method and therapeutic target for MASH."

Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus • IL1B • IL6 • TNFA

The Dual Glucagon and Glucagon-Like Peptide 1 Receptor Agonist Mazdutide Outbalanced Glucagon-Like Peptide 1 Receptor Agonist Semaglutide Monotherapy in Improving Mice Liver Fat Accumulation (ADA 2025) - "The dual GCGR/GLP-1R agonist mazdutide exhibited a better efficacy in body weight loss and liver fat accumulation alleviation compared to the GLP-1R agonist semaglutide monotherapy potentially due to its promotion of fatty acid oxidation via ATF3."

Monotherapy • Preclinical • Metabolic Disorders • Obesity • ATF3 • EHHADH • FGF21 • GDF15

Mazdutide, a Dual GLP-1R/GCGR Agonist, Reduces Hyperuricemia by Modulating Energy and Lipid Metabolism and Inhibiting Hepatic Purine Metabolism (ADA 2025) - "Mazdutide significantly lowers serum uric acid levels in hyperuricemic rats by enhancing fatty acid oxidation and regulating energy metabolism in hepatocytes, ultimately reducing purine precursor production and utilization.Compared to Semaglutide, Mazdutide offers more substantial benefits in lowering uric acid levels."

Metabolic Disorders • ACACA • ACOX1 • APOA1 • CD73 • CPT1A • FABP1 • FASN • NT5E

Innovent announces the Phase 3 Clinical Study DREAMS-1 of Mazdutide in China were Orally Presented at ADA 85th Scientific Sessions (PRNewswire) - P3 | N=319 | DREAMS-1 (NCT05628311) | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "Mazdutide demonstrated robust glucose-lowering efficacy, achieving HbA1c reduction of 2.15% after 24 weeks of treatment...For the efficacy estimand, the change in HbA1c from baseline to week 24 were -1.57% and -2.15% for mazdutide 4 mg and mazdutide 6 mg, respectively, demonstrating superiority to placebo (-0.14%). At week 24, 68.6% and 87.4% of participants receiving mazdutide 4 mg and 6 mg, respectively, achieved HbA1c <7.0% compared to 10.7% with placebo. Additionally, 55.6% and 81.5% of participants receiving mazdutide 4 mg and 6 mg, respectively, achieved HbA1c ≤6.5%, compared to 4.4% with placebo...Mazdutide was well tolerated, with low incidence of TEAEs leading to treatment discontinuation."

P3 data • Type 2 Diabetes Mellitus

Innovent Announces Completion of First Participant Dosed in the Seventh Phase 3 Clinical Trial (GLORY-OSA) of Mazdutide in China (PRNewswire) - "Innovent Biologics...announced that the first participant has been successfully dosed in a Phase 3 clinical trial (GLORY-OSA) of mazdutide, a dual glucagon (GCG) and glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity (BMI ≥ 28 kg/m2)....GLORY-OSA is a multicenter, randomized, open-label Phase 3 clinical study (NCT06931028) comparing the efficacy and safety of mazdutide 9mg versus placebo in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity (BMI ≥ 28 kg/m2).The primary endpoint is the change in apnea-hypopnea index (AHI) from baseline to Week 48."

Trial status • Obesity • Obstructive Sleep Apnea

Innovent to Present Multiple R&D Results of General Biomedicine Pipeline at the ADA’s 85th Scientific Sessions (PRNewswire) - "Innovent Biologics, Inc....announces that it will present multiple clinical study results of mazdutide at the American Diabetes Association's (ADA) 85th Scientific Sessions in Chicago, U.S. from June 20 -23. Innovent will orally present the first Phase 3 study of mazdutide in Chinese adults with T2D (DREAMS-1). In addition, multiple exploratory MoA analyses of mazdutide as well as preclinical study of IBI3030 (PCSK9-GGG antibody-peptide-conjugate) will be showcased in poster presentations."

P3 data • Cardiovascular • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis. (PubMed, EBioMedicine) - "Our findings indicate that mazdutide, via its dual GLP-1/GCGR activation effects, exerts multifactorial improvements in cognitive function in the context of obesity and T2DM. These results suggest that mazdutide is a promising therapeutic option for mitigating cognitive deficits associated with metabolic disorders."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Tolerance and Pharmacokinetic/Pharmacokinetic Study of IBI362 15mg in Patients With Moderate to Severe Obesity (clinicaltrials.gov) - P1/2 | N=98 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New P1/2 trial • Genetic Disorders • Obesity

Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. (PubMed, N Engl J Med) - P3 | "In Chinese adults with overweight or obesity, once-weekly mazdutide at a dose of 4 mg or 6 mg for 32 weeks led to clinically relevant reductions in body weight. (Funded by Innovent Biologics; GLORY-1 ClinicalTrials.gov number, NCT05607680.)."

Journal • Genetic Disorders • Obesity

Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM) (PRNewswire) - P3 | N=610 | GLORY-1 (NCT05607680) | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | "The study results showed that mazdutide significantly reduced body weight compared to placebo at both 4 mg and 6 mg doses. Based on the efficacy estimand, the mean percent change from baseline in body weight was −10.97%, −13.38%, and −0.24% at Week 32 and −12.05%, −14.84%, and −0.47% at Week 48 in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. A total of 76.3% of participants in the mazdutide 4 mg group and 84.0% in the mazdutide 6 mg group had a weight reduction of ≥5% at week 32, compared with 10.9% in the placebo group; 37.0% of participants in the mazdutide 4 mg group and 50.6% in the mazdutide 6 mg group had a weight reduction of ≥15% at week 48, compared with 2.1% in the placebo group....Mazdutide is expected to launch in China this year..."

Launch non-US • P3 data • Obesity

Second Head-to-head Phase 3 Study of Mazdutide versus Semaglutide Completes First Participant Dosing in Adults in China with Overweight or Obesity Accompanied Fatty Liver Disease (GLORY-3) (PRNewswire) - "Innovent Biologics...announces that the first participant has been successfully dosed in GLORY-3, a Phase 3 clinical study of mazdutide (Innovent R&D Code: IBI362), a dual glucagon (GCG) and glucagon-like peptide 1 receptor (GLP-1) receptor agonist. The study targets adults in China with overweight or obesity accompanied metabolic dysfunction-associated fatty liver disease (MAFLD). GLORY-3 is a multicenter, randomized, open-label Phase 3 clinical study (NCT06884293) comparing the efficacy and safety of mazdutide versus semaglutide in Chinese adults with overweight or obesity accompanied MAFLD. This study plans to enroll approximately 470 participants with overweight or obesity (BMI ≥ 27 kg/m2) accompanied MAFLD, who will be randomized 1:1 to receive mazdutide 9 mg or semaglutide 2.4 mg."

Trial status • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Study Comparing IBI362 vs Semaglutide in Chinese Overweight or Obese Adults With Metabolic Dysfunction-associated Fatty Liver Disease （MAFLD） (clinicaltrials.gov) - P3 | N=470 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

A Study of IBI362 in Subjects With HFpEF or HFmrEF Combined With Obesity (clinicaltrials.gov) - P2 | N=141 | Recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

A Study to Evaluate Mazdutide Compared With Placebo in Participants With Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)