AbstractBackgroundThe effect of sodium glucose transporter 2 (SGLT‐2) inhibitors is dependent on the glomerular filtration rate. It has been reported that caffeine intake increases glomerular filtration rate. However, the effect of caffeine intake on urinary glucose excretion in patients who take SGLT‐2 inhibitors is unclear.MethodsSix patients with type 2 diabetes took part in a randomized, open‐label, crossover pilot study. The patients took SGLT‐2 inhibitors (ipragliflozin) for 9 days. On day 3, 6 and 9, the patients were assigned to one of three studies: Water 500, patients drank 500 mL of water in 3 h; Water 1500, patients drank 1500 mL of water in 3 h; and Caffeine 500, patients drank 500 mL of water with 400 mg of caffeine in 3 h. In all of the studies, the patients' urine was collected over a 6‐h period. In addition, we enrolled 60 patients with type 2 diabetes who newly took SGLT‐2 inhibitors in a 3‐month follow‐up cohort study to investigate the effect of caffeine intake on glucose control. Caffeine intake was evaluated using questionnaires.ResultsThe 6‐h median (interquartile range) urinary glucose excretion was 9.5 (8.5–9.7) g in Water 500, 12.2 (10.3–27.2) g in Water 1500 and 15.7 (11.4–21.4) g in Caffeine 500 (p = 0.005 vs Water 500). In the cohort study, multiple regression analysis demonstrated that log (caffeine intake) was associated with a change in HbA1c (β = −0.299, p = 0.043) after adjusting for covariates.ConclusionsCaffeine intake enhanced the effect of SGLT‐2 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.