Background: Tofogliflozin (TOFO) has the highest selectivity to sodium-glucose co-transporter 2 (SGLT2) relative to SGLT1 (2900 times) and does not promote urinary glucose excretion at hypoglycemia compared with phlorhizin and does not enhance further lowering of glucose. To compare the impact of TOFO and ipragliflozin (IPR) on hypoglycemia in patients with T2DM, treated with sulfonylureas.

Methods: 30 patients were allocated to either 20 mg TOFO or 50 mg IPR and wore a continuous glucose monitoring (CGM, ipro2®) for 5 days at 3 times in a cross-over manner. The primary outcome measure was proportion of time over 24 hours with glucose less than 70 mg/dl detected by CGM and this was compared between two SGLT2 inhibitors.

Results: The percent time spent at glucose less than 70 mg/dl was 0.48, 2.77 and 0.06%, before treatment with SGLT2 inhibitors and treatment with IPR and TOFO (p=0.1135, between SGLT2 inhibitors). The addition of either IPR or TOFO to sulfonylureas markedly and significantly improved other CGM-derived parameters including average glucose, standard deviation of glucose, mean postprandial glucose excursion, percent time with glucose >140, >180 and >200 mg/dl, area over the curve <70, area under the curve >140, >180 and >200, maximum glucose. However, there were no significant differences in these parameters between the SGLT2 inhibitors. We also conducted a sub-analysis in 16 patients who received DPP-4 inhibitors. The results showed the percent time at glucose level <70 mg/dl (p=0.1118, between SGLT2 inhibitors) and the area over the curve <70 (p=0.0631, between SGLT2 inhibitors), tended to be lower in patients treated with TOFO.

Conclusion: Based on the CGM the addition of TOFO to sulfonylureas tended to decrease the percent time spent in hypoglycemia in T2DM. The addition of SGLT2 inhibitors to sulfonylureas improved the average glucose level and reduced glucose fluctuations without increasing hypoglycemia.


A. Kurozumi: None. Y. Okada: None. Y. Goshima: None. T. Otsuka: None. M. Narisawa: None. K. Torimoto: None. Y. Tanaka: None.

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