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To evaluate the efficacy and safety of domestic semaglutide injection in the treatment of type 2 diabetes mellitus (T2DM) inadequately controlled with metformin.

This multicenter, randomized, positive-controlled phase 3 equivalence clinical trial enrolled patients with T2DM from 39 research centers in China between March 13, 2024, and April 9, 2025. Central randomization was performed using interactive response technology, and the subjects were stratified according to their glycated hemoglobin A_1c (HbA_1c) levels (<8.5% and ≥8.5%) and randomly divided into an experimental group (domestic semaglutide injection) and a control group (original semaglutide injection) at a ratio of 1∶1. The primary endpoint was the change from baseline in HbA_1c at week 32, with an equivalent threshold of ±0.4%. The key secondary endpoints included HbA_1c change from baseline at week 20, the proportion of patients with HbA_1c<7.0% or HbA_1c≤6.5% at 20 and 32 weeks, and the evaluation of safety. Efficacy endpoints were analyzed in the full analysis set (FAS), and safety endpoints were analyzed in the safety set (SS). Changes from baseline in HbA_1c were analyzed using a mixed model for repeated measures; the proportions of subjects with HbA_1c<7.0% or HbA_1c≤6.5% were compared using the Cochran-Mantel-Haenszel χ² test; and safety endpoints were analyzed using Fisher′s exact test.

Both the FAS and SS included 481 patients, with 241 in the experimental group and 240 in the control group. After 32 weeks of treatment, the least squares mean (LSM) (95%CI) changes from baseline in HbA_1c were -1.80% (-1.93%--1.68%) in the experimental group and -1.85% (-1.98%--1.72%) in the control group, with a difference of 0.05% (-0.13%-0.23%)(both one-sided P<0.001). Similarly, equivalence was demonstrated at week 20, with an intergroup difference (95%CI) of 0.08% (-0.10%-0.26%) for the change from baseline in HbA_1c (both one-sided P<0.001). The proportions of patients achieving HbA_1c<7.0% or HbA_1c≤6.5% showed no statistically significant differences between the two groups. The incidence of overall adverse events was comparable between the two groups [85.06% (205/241) vs 83.33% (200/240)], and the incidences of drug-related hypoglycemic events were 0.41% (1/241) and 2.50% (6/240), respectively, with no statistically significant differences (both P>0.05).

In patients with T2DM inadequately controlled by metformin, domestic semaglutide injection demonstrated glucose-lowering efficacy equivalent to original semaglutide injection over the 32-week short-term period, with generally similar overall safety profiles between the two groups.

The endothelial glycocalyx is a crucial structure lining the surface of endothelial cells and participates in a variety of important physiological functions. In clinical practice, various factors can lead to glycocalyx injury and degradation, thereby causing disturbances in the internal environment of the body, further disrupting the interactive homeostasis between the internal environment and vital organs, and ultimately resulting in impairment of vital organ function. This article focuses on reviewing the factors that cause glycocalyx damage during the perioperative period, as well as the interactive effects between such damage and vital organ function. By adopting measures to protect or repair the glycocalyx, glycocalyx homeostasis can be maintained, thereby protecting the internal environment and organ function.