Innovent's Mazdutide Approved in China for Glycemic Control in Type 2 Diabetes

Analysis reveals significant industry trends and economic implications

Release Date

2025-09-19

Category

Drug Approval Event

Reference

Source

Breakthrough Clinical Results

Innovent Biologics announced that China's NMPA has approved mazdutide, a first-in-class dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, for glycemic control in adults with type 2 diabetes (T2D). The approval was based on Phase 3 clinical trials (DREAMS-1 and DREAMS-2) demonstrating mazdutide's superiority over placebo or dulaglutide in glycemic control and weight reduction. Mazdutide addresses the critical needs of long-term glucose management and complication prevention in T2D, supporting the 'Healthy China 2030' vision.

Key Highlights

  • Mazdutide is the world's first dual GCG/GLP-1 receptor agonist approved for glycemic control in adults with T2D.
  • Phase 3 trials (DREAMS-1 and DREAMS-2) showed mazdutide's superiority over placebo or dulaglutide in glycemic control and weight reduction.
  • Mazdutide demonstrated improvements in multiple cardiometabolic, hepatic, and renal parameters.
  • The mazdutide injection device features a hidden needle and is designed for single-use, enhancing patient comfort and safety.

Incidence and Prevalence

Latest Estimates of Type 2 Diabetes Incidence and Prevalence Globally

Global Burden

Type 2 diabetes mellitus (T2DM) has become a global epidemic and a rapidly growing health concern worldwide. According to the International Diabetes Federation, the number of adults (aged 20-79) diagnosed with diabetes mellitus has increased dramatically from 285 million in 2009 to 463 million in 2019. Type 2 DM comprises 95% of all diabetes mellitus patients globally.

Currently, T2DM is considered a global silent killer, affecting more than 450 million adults worldwide. The World Health Organization (WHO) reports that diabetes kills more than one million people annually, with almost 80% of deaths occurring in low- and middle-income countries. Almost half of diabetes deaths occur in people under 70 years of age, and 55% of diabetes deaths are in women. WHO projections indicate that diabetes deaths will double between 2005 and 2030.

Recent Incidence Data

The annual incidence of T2DM varies significantly across populations:

  • According to 2024 data from Japan, the annual incidence was estimated at 3.03% (95% CI: 2.21%-3.85%), ranging between 1.2% and 4.6%
  • A 2024 study found that over an average 8.8-year follow-up period, 6.05% of participants developed T2DM
  • The 10-year diabetes incidence was 8.30% in men and 6.20% in women, with men having a significantly higher risk (odds ratio 1.37)
  • The Korean Genome and Epidemiology Study (2022) reported that 19.2% of participants developed T2DM during the follow-up period

Prevalence Variations by Region and Population

Prevalence rates show significant regional and demographic variations:

  • A Japanese study reported an overall prevalence of 26.3%, with diabetes medication usage at 12.1% and insulin usage at 2.0%
  • In Swaziland, a 2020 study found the crude prevalence was 7.3% with age-adjusted rates of 3.9%
  • Among people with alcohol use disorders, the prevalence was 12.4%
  • In the United States, historical data indicated that diabetes affected 25.8 million people (2005-2008), including 7 million undiagnosed cases
  • Among US residents 65 years and older, 26.9 percent had diabetes in 2010

Ethnic Disparities

Significant ethnic disparities exist in T2DM prevalence:

  • South Asians have a high genetic predisposition to T2DM
  • In the US, Filipinos show higher prevalence (16.1%) compared to other high-risk groups like Latinos (14.0%), Black (13.7%), and Native Americans (13.4%)
  • Southeast Asians have 10.5% T2DM prevalence
  • Vietnamese have 9.9% prevalence compared to Whites (7.7%)
  • Asian Indians living in the US have significantly higher prevalence (17.49%) compared to those living in India (9.69%)
  • Asian-Americans collectively have higher rates of undiagnosed T2D compared to other racial/ethnic groups in the US

Risk factors associated with Type 2 diabetes include older age, obesity, family history, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race.

Emerging End Points

Emerging Endpoints for Type 2 Diabetes

Recent studies (2021-2024) reveal a significant shift in how Type 2 Diabetes Mellitus (T2DM) treatments are evaluated, with endpoints expanding well beyond traditional glycemic control measures.

Cardiovascular Endpoints

Cardiovascular outcomes have become critical endpoints in T2DM treatment evaluation. Landmark trials including EMPA-REG OUTCOME, SUSTAIN-6, LEADER, and IRIS have demonstrated convincing effects of medications like empagliflozin, liraglutide, and pioglitazone on cardiovascular disease outcomes. Researchers now commonly measure Major Adverse Cardiac and Cerebrovascular Events (MACCEs) in T2DM patients with coronary heart disease, including all-cause death, cardiac death, non-fatal MI, and unplanned revascularization.

The UTOPIA trial is evaluating tofogliflozin's effects on atherosclerosis progression using carotid intima-media thickness (IMT) as a marker of cardiovascular disease. Studies are also examining how T2DM modifies the efficacy of heart rate-reducing therapy on mortality in heart failure patients.

Renal Endpoints

Kidney function has emerged as a crucial endpoint, with researchers measuring composite kidney outcomes including ≥40% eGFR decline, end-stage kidney disease (ESKD), or death due to kidney disease in T2DM patients with moderate-to-severe CKD.

Glycemic Variability Metrics

Beyond simple HbA1c measurements, glycemic variability is now assessed through multiple metrics: - Coefficient of variation (CV) - Standard deviation (SD) - Variability independent of mean (VIM) - Time in range (TIR)

Novel Composite Endpoints

Researchers are developing composite ordinal outcomes that combine the occurrence of death and adverse events in an increasing scale of severity. This approach addresses outcome truncation by death in T2DM treatment studies and allows for simultaneous comparison of intervention effects on death and adverse events.

Medication-Related Endpoints

Drug-related problems (DRPs) are being measured in hospitalized T2DM patients, with prevalence ranging from 7% to 94%. Common DRPs include drug-drug interaction (DDI), adverse drug reaction (ADR), therapeutic effectiveness problems, and inappropriate medication use.

Patient-Centered Outcomes

Psychological aspects are increasingly recognized, with studies measuring diabetes distress (DD) and anxiety using the Diabetes Distress Scale (DDS) and Generalized Anxiety Disorder (GAD) Scales.

Emerging Non-Traditional Endpoints

Beyond traditional measures, researchers are investigating effects on nonalcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome (PCOS), and cancer risk reduction.

Despite the emergence of newer medications showing cardiovascular benefits, studies indicate that approximately 85% and 93% of eligible individuals with very high cardiovascular risk did not receive SGLT-2 inhibitors and GLP-1 receptor agonists respectively in 2022, highlighting a significant treatment gap.

These evolving endpoints reflect a more comprehensive approach to T2DM management that extends beyond glycemic control to address the multisystem impact of the disease and its treatments.

Drugs Being Trialed for Obesity/Overweight with Similar Mechanism of Action as Mazdutide

Similar Drugs

Mazdutide is a novel once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist being studied for weight loss in overweight or obese individuals. Several other drugs with similar mechanisms of action are also in development:

  • Cotadutide: Another GLP-1 and glucagon receptor dual agonist
  • Tirzepatide: A dual agonist (GLP-1/GIP) that is "the first approved dual agonist for T2D and obesity management"
  • Survodutide: A dual agonist currently in phase 3 clinical trials
  • Retatrutide: A triple agonist in clinical development
  • Cagrilintide/semaglutide combination: Currently in phase 3 clinical trials

These dual or triple receptor agonists (GLP-1 plus glucose-dependent insulinotropic polypeptide and/or Glucagon receptor) are generally more effective for weight loss than GLP-1 receptor agonists alone.

Intervention Models

The clinical trials for these medications employ several intervention models:

  1. Randomized, placebo-controlled, multiple-ascending-dose trials (as seen with Mazdutide)
  2. Double-blind, placebo-controlled trials (used in Mazdutide phase 2 and 3 trials)
  3. Phase 1b trials with dose escalation (Mazdutide was tested at doses up to 9mg and 10mg)
  4. Phase 2 trials with multiple dose arms (Mazdutide was tested at 3mg, 4.5mg, and 6mg doses)
  5. Phase 3 trials with fixed doses (Mazdutide was tested at 4mg and 6mg doses)

Most trials for these medications follow similar designs with:

  • Randomized allocation of participants
  • Treatment periods ranging from 12 weeks to 48 weeks
  • Dose escalation protocols to improve tolerability
  • Primary endpoints typically measuring percentage change in body weight
  • Secondary endpoints including changes in waist circumference, HbA1c, and other metabolic parameters

Efficacy Comparison

A network meta-analysis of these treatments showed varying degrees of effectiveness:

  • Retatrutide 12mg (-22.10% in body weight) and retatrutide 8mg (-20.70%) were the most efficacious treatments
  • Tirzepatide 15mg (-16.53%) was the third most efficacious
  • Mazdutide at 6mg showed -14.01% weight reduction at 48 weeks in phase 3 trials

These findings highlight the promising potential of multi-receptor agonists in the treatment of obesity and overweight conditions, with newer agents showing increasingly impressive weight loss results in clinical trials.