Comparative Efficacy and Safety of Oral Semaglutide in Asians and Non-Asians Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Introduction: 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. Methods: 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]). Results: 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. Conclusions: 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.