title: Efficacy of Mitiglinide Combined with Dapagliflozin in Streptozotocin-nicotinamide-induced Type 2 Diabetic Rats and in Zucker Fatty Rats.
abstract: The efficacy of the combination of the rapid-acting insulin secretagogue mitiglinide and the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was explored in streptozotocin-nicotinamide-induced type 2 diabetic (STZ-NA) rats and in Zucker fatty (ZF) rats. The STZ-NA rats were prepared at 8 weeks of age. At 9 weeks of age, the combination study was conducted by oral glucose tolerance test (OGTT). At 13 weeks of age, ZF rats were dosed orally with dapagliflozin once daily up to the 22(nd) day. At days 15 and 22, the combination study was conducted by OGTT. In 2 different animal models, plasma glucose levels were strongly suppressed by the combination of mitiglinide and dapagliflozin as compared with either drug alone. The urinary glucose excretion was drastically elevated in the dapagliflozin group, but the combination with mitiglinide suppressed it about 50%. In STZ-NA rats, the plasma insulin secretion by the combination of both drugs was about at the same level as in the mitiglinide group. In ZF rats, the plasma insulin secretion by the combination of both drugs was less than mitiglinide group. Thus, in 2 different animal models, the combination of mitiglinide and dapagliflozin showed stronger antihyperglycemic action accompanied by less insulin secretion than mitiglinide alone, and reduced the urinary glucose excretion as compared with dapagliflozin used alone. These results indicate that the combination of mitiglinide and dapagliflozin can be a promising combination for the treatment of diabetic patients.
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akahane
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yaguchi
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ojima
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kiguchi
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Pharmacology Research Laboratory R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D005960:Glucosides / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D054833:Isoindoles / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D054833:Isoindoles; C529054:dapagliflozin; D009536:Niacinamide; D013311:Streptozocin; C087255:mitiglinide