Wang Tianzuo, Cui Yuying, Liao Lin
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical, University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, China.
Traditional Chinese Medicine Hospital affiliated to Binzhou Medical College, Binzhou, China.
Diabetes Ther. 2025 Mar;16(3):449-470. doi: 10.1007/s13300-024-01689-1. Epub 2025 Jan 11.
More than half of diabetes patients are Asians, and their tolerance to antidiabetic drugs may differ from that of non-Asians. Oral semaglutide has recently gained attention for its advantages in glycemic and body weight control. However, its effects across different ethnic groups remain unknown.
All available databases of randomized controlled trials (RCTs) on oral semaglutide in patients with type 2 diabetes mellitus were included. These databases provided detailed patient information, including HbA1c levels, body weight, and adverse events (AEs and serious adverse events [SAEs]).
Ten randomized controlled trials involving 7817 patients were included: six conducted in European and American populations and four in East Asian populations. In both the Asian and non-Asian patients' subgroups, oral semaglutide 3, 7, and 14 mg was more effective in reducing HbA1c than placebo, and between-subgroups analysis showed that semaglutide 3, 7, and 14 mg was more effective in reducing HbA1c in the Asian patients' subgroup than in the non-Asian patients' subgroup. There were no significant differences between subgroups in the number of patients achieving HbA1c < 5%. Non-Asian patients with type 2 diabetes showed significant weight reduction with 7 mg and 14 mg oral semaglutide, and Asian patients reduced body weight only with 14 mg oral semaglutide. Between-subgroups analysis showed that 7 mg oral semaglutide was more effective for weight reduction in non-Asian patients than in Asian patients. In the analysis of the efficacy of oral semaglutide at weeks 26 and 52 in Asian and non-Asian patients, in Asian patients, the hypoglycemic efficacy of oral semaglutide at 3-, 7-, and 14-mg doses at week 52 was significantly lower than that at week 26. In non-Asian patients, there was no significant difference in the reducing HbA1c efficacy of these doses of oral semaglutide at weeks 26 and 52. The weight-reduction efficacy of all doses of oral semaglutide did not change significantly with treatment duration in either Asian or non-Asian patients. Compared with sitagliptin, oral semaglutide was more effective in HbA1c reduction and weight reduction in both Asian and non-Asian patients. Subgroup analysis showed that compared with sitagliptin, Asian patients received oral semaglutide to achieve greater efficacy (HbA1c and weight reduction) than non-Asian patients. In the analysis of adverse events, oral semaglutide, as compared with placebo, was not associated with serious adverse events in either subgroup. The incidence of other (not including series) adverse events was significantly higher in non-Asian patients receiving 7 mg and 14 mg oral semaglutide.
Oral semaglutide demonstrates superior efficacy in reducing HbA1c levels and a rapid onset of action in Asian patients. However, its efficacy appears to diminish with prolonged treatment in this population. Medium (7 mg)-dose oral semaglutide was associated with greater weight reduction in non-Asian patients than in Asian patients, but this difference was eliminated with higher doses. Additionally, doses of 7 mg or more of oral semaglutide are associated with a higher incidence of side effects in non-Asian patients.
超过半数的糖尿病患者为亚洲人，他们对抗糖尿病药物的耐受性可能与非亚洲人不同。口服司美格鲁肽因其在血糖和体重控制方面的优势，近来受到关注。然而，其在不同种族群体中的效果仍不明确。
纳入所有关于口服司美格鲁肽治疗2型糖尿病患者的随机对照试验（RCT）的可用数据库。这些数据库提供了详细的患者信息，包括糖化血红蛋白（HbA1c）水平、体重以及不良事件（AE和严重不良事件[SAE]）。
纳入了10项涉及7817例患者的随机对照试验：6项在欧美人群中开展，4项在东亚人群中开展。在亚洲和非亚洲患者亚组中，口服3、7和14毫克司美格鲁肽在降低HbA1c方面均比安慰剂更有效，亚组间分析显示，3、7和14毫克司美格鲁肽在亚洲患者亚组中降低HbA1c的效果比在非亚洲患者亚组中更显著。在HbA1c＜5%的患者数量方面，亚组间无显著差异。2型糖尿病非亚洲患者口服7毫克和14毫克司美格鲁肽后体重显著减轻，而亚洲患者仅口服14毫克司美格鲁肽后体重减轻。亚组间分析显示，7毫克口服司美格鲁肽在非亚洲患者中的减重效果比在亚洲患者中更显著。在分析亚洲和非亚洲患者在第26周和第52周时口服司美格鲁肽的疗效时，在亚洲患者中，第52周时3毫克、7毫克和14毫克剂量的口服司美格鲁肽的降糖疗效显著低于第26周。在非亚洲患者中，这些剂量的口服司美格鲁肽在第26周和第52周降低HbA1c的疗效无显著差异。在亚洲和非亚洲患者中，所有剂量的口服司美格鲁肽的减重疗效均未随治疗时间显著变化。与西格列汀相比，口服司美格鲁肽在亚洲和非亚洲患者中降低HbA1c和减轻体重方面均更有效。亚组分析显示，与西格列汀相比，亚洲患者口服司美格鲁肽比非亚洲患者获得了更大的疗效（降低HbA1c和减轻体重）。在不良事件分析中，与安慰剂相比，口服司美格鲁肽在两个亚组中均未出现严重不良事件。接受7毫克和14毫克口服司美格鲁肽的非亚洲患者中其他（不包括系列）不良事件的发生率显著更高。
口服司美格鲁肽在降低亚洲患者HbA1c水平方面显示出卓越疗效且起效迅速。然而，在该人群中，其疗效似乎会随着治疗时间延长而减弱。中等剂量（7毫克）的口服司美格鲁肽在非亚洲患者中的减重效果比在亚洲患者中更显著，但高剂量时这种差异消失。此外，7毫克或更高剂量的口服司美格鲁肽在非亚洲患者中与更高发生率的副作用相关。
