Hengrui and Kailera Present Clinical Data for HRS9531 and HRS-7535 at ADA 2025

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-17

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Jiangsu Hengrui Pharmaceuticals and Kailera Therapeutics announced the presentation of six abstracts at the American Diabetes Association's 85th Scientific Sessions. The abstracts highlight clinical progress of two drugs: HRS9531 (KAI-9531), a GLP-1/GIP dual receptor agonist, and HRS-7535 (KAI-7535), a GLP-1 receptor agonist. Data presented includes results from Phase 1 and 2 clinical trials evaluating the efficacy and safety of these drugs in participants with type 2 diabetes and obesity. Both injectable and oral formulations of HRS9531 are being studied. The data will be published online in the journal Diabetes® and on the Kailera website.

Key Highlights

  • Six abstracts presented at the ADA 85th Scientific Sessions showcasing HRS9531 and HRS-7535.
  • Phase 1 and 2 clinical trial data for HRS9531 (GLP-1/GIP dual agonist) in type 2 diabetes and obesity.
  • Phase 2 clinical trial data for HRS-7535 (GLP-1 receptor agonist) in type 2 diabetes and obesity.
  • Data covers both injectable and oral formulations of HRS9531.

Incidence and Prevalence

Global Burden of Type 2 Diabetes

The global burden of type 2 diabetes continues to rise at an alarming rate, posing a significant challenge to healthcare systems worldwide. Several studies from PubMed provide insights into the latest estimates and trends:

  • 2019 Estimates:

  • Prevalence: A study estimated a global diabetes prevalence of 9.3% in 2019, representing 463 million people. This number was projected to rise to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. Half of those living with diabetes were estimated to be undiagnosed. The prevalence was higher in urban areas (10.8%) compared to rural areas (7.2%) and in high-income countries (10.4%) compared to low-income countries (4.0%).

  • 2017 Estimates:

  • Prevalence: In 2017, approximately 462 million individuals were affected by type 2 diabetes, corresponding to 6.28% of the world's population. This translated to a prevalence rate of 6059 cases per 100,000. The prevalence was distributed across age groups as follows: 4.4% of those aged 15-49 years, 15% of those aged 50-69, and 22% of those aged 70+. Over 1 million deaths per year were attributed to diabetes, making it the ninth leading cause of mortality.

  • Incidence: Global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, respectively, in 2017, with projections for 2025 reaching 26.6 million, 570.9 million, 1.59 million, and 79.3 million, respectively. The trend for type 2 diabetes mirrored that of total diabetes, while the global age-standardized rate of mortality and DALYs for type 1 diabetes declined.

  • 2021 Estimates (Older Adults):

  • Among older adults (≥65 years), the global age-standardized prevalence and mortality of T2DM increased by 1.9% and 0.32% per year, respectively, from 1990 to 2021. The proportion of total DALYs and mortality from all diseases attributable to T2DM increased, as did its share of T2DM cases across all age groups. Mortality rose fastest in the 85-89 age group (0.52% annually). High-SDI regions had the highest prevalence, while lower SDI correlated with higher mortality rates.

  • Trends and Projections:

  • The burden of diabetes is rising globally, with faster rates in developed regions. The gender distribution is roughly equal, and incidence peaks around 55 years of age. Projections indicate a continued rise in prevalence across all world regions, with particular concern for increasing prevalence in lower-income countries.

  • By 2030, the global prevalence of type 2 diabetes is projected to increase to 7079 individuals per 100,000.

  • Risk Factors:

  • Low Physical Activity: A leading risk factor for T2DM. The global burden of low physical activity-related T2DM has continued to increase, particularly in low-middle and middle SDI regions.

  • Obesity: A significant risk factor for diabetes development. Both obesity and diabetes rates have been increasing, posing higher mortality risks and healthcare costs.

  • Other Factors: Nutrition transitions, urbanization, sedentary lifestyles, genes, early-life exposures, and high BMI are also contributing factors.

These findings highlight the urgent need for public health interventions and clinical preventive measures to address the growing diabetes epidemic.

Emerging Mechanism of Action

Several key mechanisms of action (MoA) are emerging for Type 2 diabetes treatment, based on recent PubMed publications:

1. Dual GIP and GLP-1 Receptor Agonism: Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown superior glucose control and weight loss compared to selective GLP-1RAs like dulaglutide. This dual agonism improves insulin sensitivity and beta-cell function, with effects beyond those attributable to weight loss alone.

2. SGLT2 Inhibition with Cardio-Renal Benefits: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) like empagliflozin have demonstrated substantial cardiovascular and renal benefits in individuals with type 2 diabetes and high CVD risk. They reduce the risk of all-cause death, major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and end-stage renal disease (ESRD). While there are increased risks of DKA and genital infections, the overall risk/benefit ratio remains favorable.

3. Mitochondrial Dysfunction Correction: Imeglimin, a first-in-class oral agent, targets defective cellular energy metabolism, a root cause of T2D. It rebalances respiratory chain activity, reduces oxidative stress, and prevents mitochondrial permeability transition pore opening, leading to improved glucose-stimulated insulin secretion (GSIS) and preservation of β-cell mass.

4. GLP-1 Receptor Agonism with Multi-System Benefits: GLP-1 receptor agonists (GLP-1 RAs), such as semaglutide, offer glucose-lowering effects through glucose-dependent insulin secretion, suppressed glucagon release, slowed gastric emptying, and increased satiety. They also demonstrate beneficial effects on cardiovascular and renal systems. Different GLP-1 RAs exhibit varying degrees of glycemic control, weight loss, cardiovascular effects, and tolerability profiles due to differences in their molecular structure and duration of action.

5. DPP-4 Inhibition for Incretin Enhancement: Dipeptidyl peptidase 4 inhibitors (DPP4i) improve glycemic control by inhibiting DPP-4 activity, thereby increasing the levels of incretin hormones like GLP-1. They have a good safety profile and low risk of hypoglycemia.

6. Berberine's Glucose-Lowering Effects: Berberine, an isoquinoline alkaloid extract, has shown promise as a hypoglycemic agent in managing type 2 diabetes. Its glucose-lowering effect is associated with baseline fasting plasma glucose (FPG) and HbA1c levels. It appears safe and does not increase the risk of hypoglycemia.

7. Focus on Cardio-Renal Outcomes: The management of type 2 diabetes has shifted from a purely glucocentric approach to a cardio-renal outcome-oriented approach. New therapies aim to reduce macrovascular and renal complications, recognizing the importance of organ protection beyond glycemic control.

8. Personalized Approaches and Precision Medicine: Research is ongoing to develop personalized approaches for glucose-lowering drugs based on individual patient characteristics. Precision medicine, including multiomics and pharmacogenomics, holds promise for targeted therapies based on disease heterogeneity.

9. Technology Integration: Technology has the potential to improve outcomes in type 2 diabetes management, although its full potential is yet to be realized.

It's important to note that research is ongoing, and the understanding of these MoAs and their clinical implications continues to evolve.

HRS-7535 (not HRS9531) is a novel, oral, small molecule glucagon-like peptide-1 receptor agonist (GLP-1RA) being investigated for the treatment of type 2 diabetes. One study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of HRS-7535 in healthy participants. This phase 1 trial consisted of single-ascending dose (SAD), food effect (FE), and multiple-ascending dose (MAD) parts. The most frequent adverse events reported with HRS-7535 were nausea and vomiting. The study concluded that HRS-7535 exhibited a safety and tolerability profile consistent with other GLP-1RAs and showed pharmacokinetics suitable for once-daily dosing. These findings support further clinical development of HRS-7535 for type 2 diabetes. There is no mention of HRS-7535 being trialled for indications other than type 2 diabetes in the provided text.