What question did this study set out to answer?

The aim is to assess the pharmacokinetic and pharmacodynamic properties of GZR102, a new insulin and GLP-1 combination for treating T2DM.

June 7, 2026

1822-P: Pharmacokinetic and Pharmacodynamic Profiles of GZR102 Injection, a Novel Once-Weekly Fixed-Ratio Combination of Insulin GZR4 and GLP-1 Analog Bofanglutide

Key Points

The aim is to assess the pharmacokinetic and pharmacodynamic properties of GZR102, a new insulin and GLP-1 combination for treating T2DM.
Characterization of potential drug-drug interactions and pharmacokinetic profiles.
Single dose administration in Sprague Dawley rats and Bama Miniature Pigs.
Pharmacodynamic evaluation in diet-induced obese and db/db mouse models over 30 days.
GZR102 showed no pharmacological interference between components with stable bioavailability.
In DIO mice, GZR102 reduced body weight by 13-25% and improved hepatic steatosis; in db/db mice, it lowered HbA1c by 1.2% to 1.6% compared to GZR4 (0.3%) and GZR18 (0.9%).

Abstract

Introduction and Objective: GZR102 injection (GZR102) is a novel once-weekly fixed-ratio combination (FRC) of insulin GZR4 and the GLP-1 analog bofanglutide (GZR18). GZR102 is designed to preserve the pharmacokinetic (PK) characteristics of the individual components while delivering complementary glycemic control and metabolic benefits in people with T2DM. Methods: Potential drug-drug interactions (DDI) were assessed. PK profiles of GZR102 and its two individual components were characterized following a single dose administered to Sprague Dawley (SD) rats and Bama Miniature Pigs. The pharmacodynamic efficacy of GZR102 was evaluated in diet-induced obese (DIO) and db/db mouse models following subcutaneous administration every three days for 30 days at multiple dose levels. Results: No pharmacological interference between GZR4 and GZR18 in the GZR102 combination was observed across a broad range of molar ratios, and no apparent competition for albumin binding was detected. The PK profile of GZR102 was comparable to those of each component when administered the same dose in rats and pigs. The absolute and relative bioavailability of each component in GZR102 were comparable to their respective mono-component injection with no meaningful alteration in clearance or exposure. GZR102 exhibited dose-dependent glucose-lowering and body weight-reducing effects in both two models. In DIO mice, GZR102 reduced body weight by 13-25%, improved high-fat diet-induced hepatic steatosis, and lowered serum lipid levels. In db/db mice, GZR102 achieved superior glycemic control versus GZR4 or GZR18 alone, with greater reductions in HbA1c (1.2% to 1.6% vs 0.3% vs 0.9%, respectively). Conclusion: The combination of GZR4 and GZR18 in GZR102 did not affect the PK of the individual components. GZR102 demonstrated complementary glycemic control and metabolic benefits including weight reduction and lipid metabolism. These findings support the further clinical development of GZR102 as a once-weekly FRC. Disclosure Y. Huang: None. A. He: None. W. Xing: None. T. Xie: None. Y. Wang: None. W. Li: None. W. Chen: None.

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