Linong Ji1, Jing Liu2, Jing Yang3, Yufeng Li4, Li Liang5, Dalong Zhu6, Quanmin Li7, Tianrong Ma8, Haiyan Xu8, Yanlan Yang9, Jiaoe Zeng10, Bo Feng11, Shen Qu12, Yiming Li13, Lizhen Ma14, Shanshan Lin15, Jianping Wang16, Wei Li17, Weihong Song18, Xiaoxing Li19, Yong Luo20, Shugang Xi21, Mei Lin22, Yu Liu23, Zerong Liang24. 1. Department of Endocrinology, Peking University People's Hospital, Beijing, China. 2. Department of Endocrinology, Gansu Provincial Hospital, Gansu, China. 3. Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi, China. 4. Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China. 5. Department of Endocrinology, The People's Hospital of Liaoning Province, Shenyang, China. 6. Department of Endocrinology, Nanjing Drum Tower Hospital (the Affiliated Hospital of Nanjing University Medical School), Nanjing, China. 7. Department of Endocrinology, General Hospital of the Rocket Forces of Chinese People's Liberation Army, Beijing, China. 8. Medical Affairs, Merck China Ltd, an affiliate of Merck KGaA, Darmstadt, Germany. 9. Department of Endocrinology, Shanxi Provincial People's Hospital, Shanxi, China. 10. Department of Endocrinology, Jingzhou Central Hospital, Jingzhou, China. 11. Department of Endocrinology, Shanghai East Hospital Affiliated to Tongji University, Shanghai, China. 12. Department of Endocrinology, Shanghai Tenth People's Hospital (Tenth People's Hospital of Tongji University), Shanghai, China. 13. Department of Endocrinology, Huashan Hospital Affiliated to Fudan University, Shanghai, China. 14. Department of Endocrinology, Hangzhou First People's Hospital, Hangzhou, China. 15. Department of Endocrinology, Beijing Shijingshan Hospital, Beijing, China. 16. Department of Endocrinology, The Second Hospital Affiliated to University of South China, Hengyang, China. 17. Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. 18. Department of Endocrinology, Chenzhou No.1 People's Hospital, Chenzhou, China. 19. Department of Endocrinology, The Third Hospital of Changsha, Changsha, China. 20. Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China. 21. Department of Endocrinology, The First Hospital of Jilin University, Jilin, China. 22. Department of Endocrinology, Wuhan Puai Hospital, Wuhan, China. 23. Department of Endocrinology, Sir Run Run Hospital Nanjing Medical University, Nanjing, China. 24. Department of Endocrinology, Chongqing Red Cross Hospital (People's Hospital of Jiangbei District), Chongqing, China.
Abstract
AIMS: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naïve Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, a 16-week treatment period and a 2-week follow-up period without treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. RESULTS: Overall, 532 patients were randomized to metformin IR (n = 267) or metformin XR (n = 265). The HbA1c LSM change was -1.61% and -1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], -0.10, 0.17). Incidences of drug-related AEs were 26.5% (n = 66) in the metformin IR-only group and 32.2% (n = 85) in the metformin XR-only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60, 5.56). The treatment difference met the predefined non-inferiority upper CI margin of 0.4% in HbA1c. CONCLUSIONS:Metformin XR was non-inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.
RCT Entities:
AIMS: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naïve Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, a 16-week treatment period and a 2-week follow-up period without treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. RESULTS: Overall, 532 patients were randomized to metformin IR (n = 267) or metformin XR (n = 265). The HbA1c LSM change was -1.61% and -1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], -0.10, 0.17). Incidences of drug-related AEs were 26.5% (n = 66) in the metformin IR-only group and 32.2% (n = 85) in the metformin XR-only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60, 5.56). The treatment difference met the predefined non-inferiority upper CI margin of 0.4% in HbA1c. CONCLUSIONS:Metformin XR was non-inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.
Authors: Jane L Tarry-Adkins; Imogen D Grant; Susan E Ozanne; Rebecca M Reynolds; Catherine E Aiken Journal: Diabetes Ther Date: 2021-06-02 Impact factor: 2.945