Aims: To compare the temporal trends in the consumption patterns of glucose lowering drugs (GLD) between Portugal and the Netherlands from 2004 to 2013 and to examine possible reasons behind the cross-national variation found. Methods: All GLD (ATC pharmacological subgroup A10B) were selected for analysis. Consumption data were obtained for the 10-year period. Portuguese and Dutch drug estimates were obtained from nationwide databases. Results: The consumption of GLD increased in Portugal from 52.9 defined daily dose per 1000 inhabitants per day (DHD) in 2004 to 70.0 DHD in 2013 and in the Netherlands from 44.9 DHD in 2004 to 50.7 DHD in 2013. In Portugal, the use of fixed-dose combinations, especially with dipeptidyl peptidase-4 inhibitors (DPP-4) increased remarkably and in 2013 represented almost a quarter of total GLD consumption. In the Netherlands, the use of combinations was residual. Conclusions: The consumption of GLD rose over the 10-year period in both countries. However, Portuguese overall consumption and costs of GLD were higher. The differentially rapid uptake of DPP-4 inhibitors in Portugal was the main driver of the cost difference. (C) 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.