PMID- 28271251 OWN - NLM STAT- MEDLINE DCOM- 20170516 LR - 20221207 IS - 1869-1889 (Electronic) IS - 1674-7305 (Linking) VI - 60 IP - 3 DP - 2017 Mar TI - Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial. PG - 225-238 LID - 10.1007/s11427-016-0409-7 [doi] AB - Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks. The patients who did not reach the glycated hemoglobin A1c (HbA1c) goal were then further randomized into glimepiride, gliclazide, repaglinide, or acarbose group for an additional 24-week triple therapy. A mean HbA1c reduction of 0.85% was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks. Further HbA1c reductions in the 24-week triple therapy stage were 0.65% in glimepiride group, 0.70% in gliclazide group, 0.61% in repaglinide group, and 0.45% in acarbose group. The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide, but not for acarbose, compared with glimepiride, when added to metformin/sitagliptin dual therapy. The incidences of adverse events (AEs) were 29.2% in the dual therapy stage and 30.3% in the triple therapy stage. Metformin/sitagliptin as baseline therapy, with the addition of a third oral antihyperglycemic agent, including glimepiride, gliclazide, repaglinide, or acarbose, was effective, safe and well-tolerated for achieving an HbA1c <7.0% goal in type 2 diabetic patients inadequately controlled with previous therapies. The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia. FAU - Xu, Wen AU - Xu W AD - Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, 510630, China. FAU - Mu, Yiming AU - Mu Y AD - Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China. muyiming@301hospital.com.cn. FAU - Zhao, Jiajun AU - Zhao J AD - Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, China. FAU - Zhu, Dalong AU - Zhu D AD - Department of Endocrinology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. FAU - Ji, Qiuhe AU - Ji Q AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. FAU - Zhou, Zhiguang AU - Zhou Z AD - Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Key Laboratory of Diabetes Immunology, Ministry of Education Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, 410011, China. FAU - Yao, Bin AU - Yao B AD - Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, 510630, China. FAU - Mao, Anhua AU - Mao A AD - Merck Sharp & Dohme China, Shanghai, 200020, China. FAU - Engel, Samuel S AU - Engel SS AD - Merck & Co, Inc., Kenilworth, NJ, 07033, USA. FAU - Zhao, Bin AU - Zhao B AD - Merck Sharp & Dohme China, Shanghai, 200020, China. FAU - Bi, Yan AU - Bi Y AD - Department of Endocrinology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. FAU - Zeng, Longyi AU - Zeng L AD - Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, 510630, China. FAU - Ran, Xingwu AU - Ran X AD - Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, 610041, China. FAU - Lu, Juming AU - Lu J AD - Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology, Peking University People's Hospital, Beijing, 100044, China. FAU - Yang, Wenying AU - Yang W AD - Department of Endocrinology, China-Japan Friendship Hospital, Beijing, 100029, China. FAU - Jia, Weiping AU - Jia W AD - Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. wpjia@sjtu.edu.cn. FAU - Weng, Jianping AU - Weng J AD - Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, 510630, China. wjianp@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20170207 PL - China TA - Sci China Life Sci JT - Science China. Life sciences JID - 101529880 RN - 0 (Blood Glucose) RN - 0 (Carbamates) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Piperidines) RN - 0 (Sulfonylurea Compounds) RN - 668Z8C33LU (repaglinide) RN - 6KY687524K (glimepiride) RN - 9100L32L2N (Metformin) RN - G4PX8C4HKV (Gliclazide) RN - T58MSI464G (Acarbose) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM CIN - Sci China Life Sci. 2017 Mar;60(3):319-320. PMID: 28271252 MH - Acarbose/adverse effects/therapeutic use MH - Adult MH - Blood Glucose MH - Carbamates/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Therapy, Combination MH - Female MH - Gliclazide/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Male MH - Metformin/adverse effects/*therapeutic use MH - Middle Aged MH - Piperidines/adverse effects/therapeutic use MH - Sitagliptin Phosphate/adverse effects/*therapeutic use MH - Sulfonylurea Compounds/adverse effects/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - DPP-4 inhibitor OT - acarbose OT - gliclazide OT - glimepiride OT - metformin OT - oral antihyperglycemic agent OT - repaglinide OT - type 2 diabetes EDAT- 2017/03/09 06:00 MHDA- 2017/05/17 06:00 CRDT- 2017/03/09 06:00 PHST- 2016/12/27 00:00 [received] PHST- 2017/01/06 00:00 [accepted] PHST- 2017/03/09 06:00 [pubmed] PHST- 2017/05/17 06:00 [medline] PHST- 2017/03/09 06:00 [entrez] AID - 10.1007/s11427-016-0409-7 [pii] AID - 10.1007/s11427-016-0409-7 [doi] PST - ppublish SO - Sci China Life Sci. 2017 Mar;60(3):225-238. doi: 10.1007/s11427-016-0409-7. Epub 2017 Feb 7.