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A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of a sodium‐glucose co‐transporter‐2 inhibitor tofogliflozin
Author(s) -
Yamasaki Nozomu,
Tamura Yoshifumi,
Kaga Hideyoshi,
Sato Motonori,
Kiya Mai,
Kadowaki Satoshi,
Suzuki Ruriko,
Furukawa Yasuhiko,
Sugimoto Daisuke,
Funayama Takashi,
Someya Yuki,
Kakehi Saori,
Nojiri Shuko,
Satoh Hiroaki,
Kawamori Ryuzo,
Watada Hirotaka
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14312
Subject(s) - chemistry , glucagon , endogeny , medicine , endocrinology , glucagon like peptide 1 , insulin , sodium , transporter , type 2 diabetes , pharmacology , diabetes mellitus , biochemistry , organic chemistry , gene
Aim To investigate whether changes in endogenous glucose production (EGP) and insulin and glucagon levels are elicited by the decrease in plasma glucose (PG) levels induced by the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor tofogliflozin. Materials and Methods We evaluated EGP in 12 Japanese patients with type 2 diabetes under the conditions of no drugs administered (CON), single administration of the SGLT2 inhibitor tofogliflozin (TOF), and single administration of TOF with adjustment of PG levels with exogenous glucose infusion to mimic changes in PG levels observed with CON (TOF + G). We evaluated changes in EGP and levels of C‐peptide and glucagon from baseline to 180 minutes after drug administration. Results Endogenous glucose production decreased in the CON (−0.22 ± 0.11 mg/kg·min) and TOF + G experiments (−0.31 ± 0.24 mg/kg·min), but not in the TOF experiment (+0.08 ± 0.19 mg/kg·min). The decrease in C‐peptide was significantly greater in the TOF experiment (−0.11 ± 0.06 nmol/L) than in the CON (−0.03 ± 0.06 nmol/L) and the TOF + G experiments (−0.01 ± 0.11 nmol/L), while the increase in glucagon was significantly greater in the TOF experiment (+11.1 ± 6.3 pmol/L), but not in the TOF + G experiment (+8.6 ± 7.6 pmol/L) compared to the CON experiment (+5.1 ± 4.3 pmol/L). Conclusions These results indicate that the decrease in PG levels induced by SGLT2 inhibitor administration is required for the increase in EGP and decrease in insulin secretion.