The aim of this study is to investigate the effect of high dose metformin or combination of low dose metformin and linagliptin on glycemic variability (GV) in Japanese type 2 diabetes (T2D) patients with insufficient glycemic control with low dose metformin alone in a cross-over study using continuous glucose monitoring (CGM). This study was conducted in T2D outpatients (7%< HbA1c <10%) receiving low dose metformin (750-1000 mg) alone. All patients were assigned to metformin 1500 mg monotherapy (high dose metformin; HMET) or combination of metformin 750 mg and linagliptin 5 mg (low dose metformin and DPP-4; LMET+DPP-4) in a cross-over fashion and underwent CGM assessments more than 4 weeks after change of treatment. 24-hour data were collected for comparison after they had had the same retort pouch foods. Mean glucose level, standard deviations of glucose (SD), glucose coefficient of variation (%CV), mean amplitude of glucose excursions (MAGE), pre-meal glucose levels, and 3-hour postprandial glucose area under the curve (AUC, >160 mg/dL) were compared between HMET and LMET+DPP-4 groups by using t-test. The study enrolled a total of 11 patients with T2D (men/women, 8/3; age, 51.9 ± 9.8 years; BMI, 26.3 ± 3.0 kg/m2; HbA1c, 7.6 ± 0.4%; and metformin dose 750/1000 mg, 6/5). Of the CGM-derived GV metrics for the HMET vs. LMET+DPP-4, mean glucose level, SD, MAGE and %CV were not significantly different (p=0.946, 0.394, 0.865, 0.290). Again, while the pre-breakfast glucose level were not significantly different between the groups (p=0.432), the AUC after breakfast was significantly smaller in LMET+DPP-4 vs. HMET (5004 ± 3220 vs. 7712 ± 5177; p=0.047). A comparison of GV with HMET vs. LMET+DPP-4 suggested that LMET+DPP-4 may reduce post-breakfast GV to a greater degree than HMET in Japanese patients with T2D receiving low dose metformin monotherapy.


H. Takahashi: None. R. Nishimura: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Abbott, Medtronic, MSD K.K., Novo Nordisk A/S, Sanofi, Takeda Development Center Asia, Pte. Ltd., Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.. K. Utsunomiya: None.

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