Which Is Better? High-Dose Metformin Alone or Combination of Low-Dose Metformin and Linagliptin on Glycemic Variability in Japanese Type 2 Diabetes Patients with Insufficient Glycemic Control with Low-Dose Metformin Alone—A Randomized, Crossover, Pilot Study

Abstract

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. Disclosure 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.