Ito Jumpei, Hagi Katsuhiko, Kochi Kenji, Ueki Kohjiro, Watada Hirotaka, Kaku Kohei
Medical Science, Sumitomo Pharma Co., Ltd., Tokyo, Japan.
Data Science, Sumitomo Pharma Co., Ltd., Tokyo, Japan.
J Diabetes Investig. 2025 Apr;16(4):629-638. doi: 10.1111/jdi.14396. Epub 2024 Dec 26.
An increased rate of gastrointestinal (GI) symptoms is reported in patients with type 2 diabetes receiving imeglimin plus metformin vs monotherapy or in combination with other antidiabetic drugs. This post-hoc analysis explored GI symptom incidence, risk factors for their occurrence, and the impact on therapeutic efficacy during imeglimin and metformin combination therapy.
Data were derived from the 52-week, open-label, phase 3 TIMES-2 trial in Japanese type 2 diabetes patients. Patients in the imeglimin plus metformin group were divided into two subgroups based on the presence of GI symptoms and diarrhea, with efficacy and safety assessed. Factors associated with their occurrence were explored using multivariate logistic regression analysis.
Of 64 patients analyzed, GI symptoms and diarrhea occurred in 40.6% (n = 26) and 17.2% (n = 11) of patients, respectively. Metformin dose and patient age did not significantly affect their incidence. Events occurred more frequently within the first 4 months of treatment. Approximately half resolved within 1 week, and most were mild. Type 2 diabetes duration <5 years was significantly associated with diarrhea (odds ratio = 5.979; P = 0.039). Significant hypoglycemic effects were observed from baseline, irrespective of GI symptoms or diarrhea. However, the degree of HbA1c improvement tended to be greater in patients with GI symptoms and diarrhea.
Increased awareness regarding the potential for GI symptoms, including diarrhea, during imeglimin plus metformin combination therapy is warranted. This data will provide clinicians with useful information regarding symptomatic treatment when it occurs and help determine whether to continue treatment administration and is expected to improve patient adherence.
据报道，接受依格列净加二甲双胍治疗的2型糖尿病患者胃肠道（GI）症状发生率高于单药治疗或与其他抗糖尿病药物联合治疗的患者。这项事后分析探讨了依格列净和二甲双胍联合治疗期间胃肠道症状的发生率、发生风险因素及其对治疗效果的影响。
数据来源于一项针对日本2型糖尿病患者的为期52周的开放标签3期TIMES-2试验。依格列净加二甲双胍组的患者根据胃肠道症状和腹泻情况分为两个亚组，并评估疗效和安全性。使用多因素逻辑回归分析探索与症状发生相关的因素。
在分析的64例患者中，分别有40.6%（n = 26）和17.2%（n = 11）的患者出现胃肠道症状和腹泻。二甲双胍剂量和患者年龄对其发生率没有显著影响。事件在治疗的前4个月内更频繁发生。约一半的症状在1周内缓解，且大多数症状较轻。2型糖尿病病程<5年与腹泻显著相关（比值比 = 5.979；P = 0.039）。无论有无胃肠道症状或腹泻，从基线开始均观察到显著的降糖效果。然而，有胃肠道症状和腹泻的患者糖化血红蛋白（HbA1c）改善程度往往更大。
在依格列净加二甲双胍联合治疗期间，有必要提高对包括腹泻在内的胃肠道症状可能性的认识。这些数据将为临床医生提供有关症状出现时对症治疗的有用信息，并有助于确定是否继续给药治疗，有望提高患者的依从性。
