2361-PUB: Enhancement of Flattening Glycemic Fluctuation in Patients with Type 2 Diabetes by SGLT2 Inhibitor Combined with DPP-4 Inhibitor
Authors: CHO KYUYONG , NOMOTO HIROSHI , NAKAMURA AKINOBU , OMORI KAZUNO , ATSUMI TATSUYA , MIYOSHI HIDEAKI 
Published: June 2019

Background and Aim: DPP-4 inhibitor is well known to flatten glucose fluctuation in patients with type 2 diabetes by exerting a hypoglycemic effect according to plasma glucose level. SGLT2 inhibitors also have powerful hypoglycemic effects depending on glucose level and renal function. However. few reports have compared them and their combination in detail.
Methods: A multicenter, open-label, parallel-group, randomized, controlled study (UMIN000029628). The key inclusion criteria were: Japanese patients with type 2 diabetes; age, 20-80 years; HbA1c, 6.5%-9.0%; BMI, ≥22 kg/m2; eGFR, ≥45 mL/min/1.73m2; and treatment with 20 mg of Teneligliptin, DPP-4 inhibitor. Participants were randomized to the combination of Canagliflozin 100 mg/Teneligliptin 20 mg (C, combination) or Canagliflozin 100 mg (S, SGLT2 inhibitor) groups. Glycemic fluctuation was evaluated with flash glucose monitoring (FreeStyle Libre Pro) during test meals for 2 days before and more than 7 days after the switching. The primary endpoint was the mean amplitude of glycemic excursions (MAGE).
Results: No significant differences were observed in the backgrounds of 50 patients in C group and 49 patients in S group. MAGE decreased significantly in C group, and the reduction was significantly larger in C group than in S group (C, 116.5 ± 39.8 to 92.2 ± 28.0 mg/dL; S, 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL, p &lt;0.01). Mean blood glucose for 24-hour decreased significantly in both groups, but the extent of the reduction was significantly larger in C group than in S group (C, 142.3 ± 41.8 to 119.5 ± 34.8 mg/dL; S, 146.4 ± 41.3 to 135.5 ± 39.8 mg/dL, p &lt;0.001). HbA1c was decreased only in C group (C, −0.4 ± 0.3%; S, −0.1 ± 0.2%, p &lt;0.01). None of the patients dropped out of the trial for adverse events.
Conclusions: SGLT2 inhibitor combined with DPP-4 inhibitor strongly flattened glycemic fluctuation compared with their single use, and this contributed to suppression of the progression of diabetic complications.

Disclosure
K. Cho: None. H. Nomoto: None. A. Nakamura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd. K. Omori: None. T. Atsumi: Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB, Inc. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding
Mitsubishi Tanabe Pharma Corporation