SGLT2 inhibitors (SGLT2is) prevent disease progression in diabetic patients with atherosclerotic disease. On the other hand, a similar beneficial effect on disease progression has not been reported for DPP-4 inhibitors (DPP-4is) , which are, however, widely used. To clarify the differences in effects between these two classes of drugs in diabetic patients, we focused on the production of advanced glycation end products (AGEs) and studied the effects of pretreatment with DPP-4i on the production of AGEs in patients who subsequently received SGLT2i. In the present study, Japanese patients with type 2 diabetes mellitus with unchanged glycemia control status for at least 6 months were administered SGLT2i (n = 11) for 3 months and then divided into a group that had already been receiving DPP-4i (n = 11) at the start of administration of the SGLT2i and the SGLT2i monotherapy group. We measured the blood levels of methylglyoxal-derived hydroimidazolone-1 (MG-H1) , which is an AGE, and also diabetes-related parameters before the start and after 3 months’ treatment with the SGLT2i. As a result, significant decreases of both HbA1c (from 8.6 ± 1.4 to 7.2 ± 1.4, P < 0.01) and circulating MG-H1 levels (from 0.48 ± 0.44 ± 0.07, P < 0.05) were observed in the SGLT2i monotherapy group. On the other hand, in the group that received SGLT2i in addition to a DPP-4i, the HbA1c value decreased significantly (from 7.2 ± 0.4 to 6.8 ± 0.5, P < 0.01) , whereas no significant change of the MG-H1 level was observed after the SGLT2i therapy. In conclusion, SGLT2i monotherapy decreased both the HbA1c and blood MG-H1 levels. However, no significant effect on the blood level of MG-H1 was observed in the combined DPP4i plus subsequent SGLT2i therapy group, suggesting that DPP4i possibly suppress the effect of the SGLT2i in reducing the production of MG-H1.


M.Kusunoki: Other Relationship; Taisho Pharmaceutical Holdings Co., Ltd. N.Wakazono: None. F.Hisano: None. T.Miyata: None.

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