886-P: Protective Effects of DPP-4 Inhibitor and SGLT2 Inhibitor on Pancreatic ß-Cell Function—Randomized, Parallel-Group, Multicenter, Open-Label Study (SECRETE-I)
Authors: SHIMODA MASASHI , KATAKURA YUKINO , IWAMOTO MASAHIRO , KIMURA YUKIKO , ANNO TAKATOSHI , ISOBE HAYATO , IWAMOTO YUICHIRO , FUSHIMI YOSHIRO , SANADA JUNPEI , OBATA ATSUSHI , KIMURA TOMOHIKO , KAWASAKI FUMIKO , TATSUMI FUMINORI , NAKANISHI SHUHEI , MUNE TOMOATSU , KAKU KOHEI , KANETO HIDEAKI 
Published: June 2023

Aims: Effects of DPP-4 inhibitor or SGLT2 inhibitor on human β-cell function are not well understood, and there is no report showing the difference between the two agents. The aim of this study is to compare the effects of these drugs on β-cell function in patients with type 2 diabetes.
Methods: The study protocol was approved by the IRB of Kawasaki Medical School (No. jRCTs061190008). A total of 103 patients met the inclusion criteria (age; 20 to 79 years, HbA1c; ≥7.0% and &lt;9.0%). Subjects were randomly assigned to luseogliflozin (L) group (n=49) or teneligliptin (T) group (n=54) and received 24 wks of intervention followed by 1-2 wks of drug washout. The primary endpoint was the change in log-transformed (Ln) disposition index (DI) 0-120 from baseline. Subjects underwent 75gOGTT before and after treatment.
Results: The main baseline backgrounds of L and T groups were as follows; age: 60.8±11.1 vs. 62.6±11.2 years (p=0.4), diabetes duration: 10.1±7.9 vs. 9.2±7.6 years (p=0.6), BMI: 27.0±4.2 vs. 27.2±5.4 kg/m2 (p=0.8), HbA1c: 7.6±0.4 vs. 7.5±0.5 % (p=0.5), DI 0-120: 0.80±0.60 vs. 0.92±0.59 (p=0.1). HbA1c levels were significantly decreased in both groups, but the amount of change was greater in the T group (-0.2%, p=0.02). Body weight was significantly decreased only in the L group, with a group difference of -2.5 kg (p&lt;0.001). Ln DI 0-120 were improved in both groups: -0.46±0.66 to -0.15±0.59 (p=0.01) in L group and -0.26±0.60 to -0.02±0.60 (p=0.003) in T group. The change in Ln serum proinsulin/CPR ratio, a marker of β-cell dysfunction, was reduced in L group (1.63±0.63 to 1.56±0.68, p=0.16), but rather increased in T group (1.70±0.75 to 1.90±0.51, p=0.01), with significant difference between the 2 groups (-0.27; p=0.004).
Conclusion: Improvement effects on DI 0-120 were almost identical between luseogliflozin and teneligliptin. On the other hand, burden on β-cells was mitigated only in luseogliflozin group.

Disclosure
M.Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. A.Obata: None. T.Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. F.Kawasaki: None. F.Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. S.Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T.Mune: None. K.Kaku: Advisory Panel; Novo Nordisk, Consultant; Sanwa Kagaku Kenkyusho, Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H.Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc., Abbott, Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Y.Katakura: Speaker's Bureau; Abbott. M.Iwamoto: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Boehringer Ingelheim Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd. Y.Kimura: None. T.Anno: None. H.Isobe: None. Y.Iwamoto: Speaker's Bureau; Kowa Company, Ltd. Y.Fushimi: None. J.Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd.

Funding
Taisho Pharmaceutical Holdings Co., Ltd.