Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats.
1. The effects of combined treatment with pioglitazone.HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when pioglitazone.HCl or metformin was administered alone and combined treatment accentuated this decrease. The administration of pioglitazone.HCl, but not metformin, also decreased plasma levels of triglyceride and total ketone bodies. 3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4. Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic Wistar fatty rats; however, concurrent administration of metformin significantly ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate that combined treatment with pioglitazone.HCl and metformin induces a marked hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These favourable effects suggest that the combination would be beneficial in treating patients with type 2 diabetes.
Suzuki
Masami
M
Pharmacology Research Laboratories II, Takeda Chemical Industries Ltd, Osaka, Japan. Suzuki_Masami@tekda.co.jp
Odaka
Hiroyuki
H
Suzuki
Noriko
N
Sugiyama
Yasuo
Y
Ikeda
Hitoshi
H
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D007657:Ketone Bodies; D013844:Thiazoles; D045162:Thiazolidinediones; D006003:Glycogen; D008687:Metformin; D000077205:Pioglitazone