Gan & Lee Pharmaceuticals' preclinical results of Class 1 innovative premixed insulin, Insulin GZR101, has been published in the long-established, authoritative pharmacology journal Naunyn-Schmiedeberg's Archives of Pharmacology. The results demonstrate that GZR101 exhibits favorable pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. In animal models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GZR101 showed superior glucose-lowering efficacy compared with the world's only marketed product in the same class, the insulin degludec/insulin aspart (IDegAsp, Ryzodeg^®), providing a solid scientific basis for further clinical research in patients with diabetes.

Premixed insulin combines basal and prandial components in a single injection. Compared with basal insulin alone, it achieves superior glycemic control without increasing the risk of hypoglycemia¹. Relative to a basal-bolus regimen, premixed insulin delivers comparable efficacy with fewer injections, a lower total insulin dose, and a reduced risk of hypoglycemia². In addition, premixed insulin does not require resuspension before injection, which significantly improves ease of use. It also reduces the "shoulder effect" (the additive overlap of the intermediate-acting and prandial components), enabling a closer mimic of the physiological biphasic pattern of insulin secretion in humans³.

Gan & Lee's investigational novel premixed insulin, GZR101, combines a novel Class 1 long-acting basal insulin analog (insulin GZR33) with a marketed rapid-acting insulin aspart (Rapilin^®). Preclinical studies demonstrate that GZR101 has favorable PK and PD profiles. The basal insulin component, GZR33, provides sustained and consistent glucose-lowering effect, and the two components in GZR101 act independently without cross-interaction4. Both GZR33 and GZR101 have shown superior glucose-lowing efficacy in T1DM and T2DM animal models.

The key findings are as follows:

• GZR33 demonstrates a gradual and sustained absorption with a prolonged half-life compared to degludec (IDeg, Insulin degludec). In Sprague Dawley (SD) rats and Beagle dogs, the half-life of GZR33 is approximately twice that of IDeg (5.5 h vs. 2.3 h in rats, 6.0 h vs. 3.2 h in dogs), with prolonged half-life (2.3-6.2 h vs. 1.5 h in rats).

• Greater glucose-lowering effect and longer duration of GZR33. In T1DM rats, the reduction of glycated hemoglobin (HbA1c) in GZR33 (-6.3%) was superior to that in IDeg (-3.3%). The glucose-lowering effect of GZR33 persisted for over 48 h, compared to 24 h for IDeg, highlighting the prolonged duration of action for GZR33. At the same molar concentration, the glucose-lowering potency of GZR33 was at least three-fold higher than that of IDeg.

• The PK profiles of GZR33 and insulin Aspart in GZR101 were observed to occur independently, without cross-interactions. The PK curves of both components in the premixed GZR101 formulation were comparable to those observed when each was administered separately, indicating no meaningful drug–drug interaction between GZR33 and aspart. These results confirm the compatibility of the two drugs while ensuring that each is capable of functioning independently.

• GZR101 has been demonstrated to exert a beneficial therapeutic effect on both T1DM rats and T2DM mice, with lowered HbA1c (T1DM: -10% vs -2.7% with IDegAsp; T2DM: -2% vs -1%).

Dr. Wei Chen, first author of the study at Gan & Lee Pharmaceuticals, stated that: "The preclinical data highlights the unique PK advantages of GZR101 and its favorable glucose-lowering efficacy in diabetic animal models, demonstraring its broad therapeutic potential for diabetes treatment. GZR101 has now advanced to phase 2 clinical development and we look forward to accelerating its progress to provide a new treatment option for patients."

Article link: https://doi.org/10.1007/s00210-025-04366-7

Reference:

1. Onishi Y, Ono Y, Rabøl R, et al. Superior glycaemic control with once‐daily insulin degludec/insulin aspart versus insulin glargine in Japanese adults with type 2 diabetes inadequately controlled with oral drugs: a randomized, controlled phase 3 trial[J]. Diabetes Obes Metab, 2013, 15(9):826‐832. DOI: 10.1111/dom.12097.

2. Philis‐Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38‐week trial comparing the IDegAsp co‐formulation with insulin glargine U100 and insulin aspart in basal insulin‐treated subjects with type 2 diabetes mellitus[J]. Diabetes Res Clin Pract, 2019, 147: 157‐165. DOI: 10.1016/j.diabres.2018.10.024.

3. 朱大龙, 赵维纲, 匡洪宇, 等. 德谷门冬双胰岛素临床应用专家指导意见 [J] . 中华糖尿病杂志, 2021, 13(7) : 695-701. DOI: 10.3760/cma.j.cn115791-20210506-00247.

4. Chen W, Cui C, Xing W, Zhang Y, He A, Wang Y, Huang Y, Zhai N, Shi Q, Xue F, Wang Y, Zhang J, Yu D, Xie T, Li Y, Gan ZR. GZR101, a Novel Premixed Insulin for the Treatment of Diabetes Mellitus. Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 18. doi: 10.1007/s00210-025-04366-7. Epub ahead of print. PMID: 40531224.

About Gan & Lee

Gan & Lee Pharmaceuticals developed the first Chinese domestic insulin analog. Currently, Gan & Lee has six core insulin products, including five insulin analog varieties: long-acting glargine injection (Basalin^®), fast-acting lispro injection (Prandilin^™), fast-acting aspart injection (Rapilin^®), mixed protamine zinc lispro injection (25R) (Prandilin^™25), aspart 30 injection (Rapilin^®30), and one human insulin injection - mixed protamine human insulin injection (30R) (Similin^®30). The company has two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine^®).

In China's 2024 National Insulin-Specific Centralized Procurement, Gan & Lee Pharmaceuticals ranked first among all selected companies in terms of procurement demand for insulin analogs. The company is also making strides in international markets and received GMP inspection approval from the European Medicines Agency (EMA) in 2024. These achievements significantly boost Gan & Lee's competitiveness in both international and domestic markets.

In the future, Gan & Lee will strive for comprehensive coverage in diabetes treatment. Moving forward with its mission to become a world-class pharmaceutical company, Gan & Lee will also actively develop new chemical entities and biological drugs, focusing on treatments for metabolic diseases, cardiovascular diseases, and other therapeutic areas.