Comparison of Metformin and Alogliptin Fixed-Dose Tablets Once a Morning Versus Once an Evening Using Continuous Glucose Monitoring (AMPM Study): An Open-Label Randomized Cross-Over Trial

Background: The aim of the study is to compare the effect of metformin hydrochloride and alogliptin benzoate combination tablets medication once daily am/pm on blood glucose and investigate predictive factors for drug responses. Methods: This is a single-center, single-dose, open-label, randomized, two-treatment (once-daily, am and pm), two-sequence and two-period crossover study with a washout period of 1 day. Glycemic variability and control were assessed using the FreeStyle Libre Pro continuous glucose monitoring in terms of time spent in different glycemic ranges and low/high blood glucose indices (LBGI/HBGI), and compared between the dosing timing. Results: The average postprandial glucose in lunch and dinner in AM group were lower but not significant compared to PM group. There was no difference in average, time above range (TAR: > 180 mg/dL), time in range (TIR: 70 - 180 mg/dL), time below range (TBR: < 70 mg/dL), and area under curve (AUC) (AM0 - AM6, AM6 - PM0, PM0 - PM6, and PM6 - PM12) between treatments time (AM vs. PM). There was a significant strong negative correlation between high-density lipoprotein cholesterol (HDL-C) levels and changes of HBGI from AM to PM (r = -0.608), but HDL-C levels were not associated with LBGI. There was moderately strong correlation between evening type in chronotype and changes of HBGI from AM to PM (r = 0.592). Conclusions: These findings suggest that HDL-C levels and chronotype might modulate drug response, although there was no difference in average, TIR, TBR, TAR, and AUC between treatments timing in patients with type 2 diabetes (T2D). J Endocrinol Metab. 2021;11(1):8-13 doi: https://doi.org/10.14740/jem720