The efficacy and safety of treatment with troglitazone combined with an α-glucosidase inhibitor, in obese type 2 diabetic patients who were previously administered α-glucosidase inhibitors alone, in improving glycaemic control and reducing insulin resistance were studied. Obese type 2 diabetic patients, poorly controlled with α-glucosidase inhibitors, were randomized to receive either oral troglitazone 200 mg twice daily (22 patients: group A) or a placebo (20 patients: group B) in addition to their usual α-glucosidase inhibitor. In group A, significant decreases in the mean levels of haemoglobin A1c and basal plasma insulin levels were observed 6 months after the start of combined therapy. Serum triglyceride levels significantly decreased but serum lactic acid dehydrogenase and body weight significantly increased. New systemic oedema was observed in six patients. Combined therapy with troglitazone and α-glucosidase inhibitors may be effective for diabetic metabolic abnormalities, although the potential development of adverse effects such as body-weight gain and systemic oedema demands vigilance.
BalfourJAMcTavishDAcarbose. An update of its pharmacology and therapeutic use in diabetes mellitus. Drugs1993; 4: 1025–1054.
2.
HoriiSFukaseHMatsuoTKamedaYSynthesis and alphaD-glucosidase inhibitory activity of N-substituted valiolamine derivatives as potential oral antiadiabetic agents. J Med Chem1986; 29: 1038–1046.
LeonhardtWHanefeldMFischerSBeneficial effects on serum lipids in non-insulin dependent diabetics by acarbose treatment. Arzneimittelforschung1991; 1: 735–438.
5.
YamadaNAkanumaYMuraseTClinical evaluation of a new oral hypoglycaemic drug CS-045 in patients with non-insulin dependent diabetes mellitus accompanying hypertriglyceridemia (in Japanese, English abstract). J Clin Ther Med1993; 9 (Suppl 3): 165–178.
6.
ToyotaTSatohJTakebeKResults of long-term combined therapy with CS-045 and insulin in patients with insulin dependent or non-insulin-dependent diabetes mellitus (in Japanese, English abstract). J Clin Ther Med1997; 13: 1533–1561.
7.
KosakaKKuzuyaTAkanumaYClinical evaluation of a new oral hypoglycaemic drug CS-045 in patients with non-insulin dependent diabetes mellitus poorly controlled by sulphonylureas – a double-blind, placebo-controlled study (in Japanese, English abstract). J Clin Ther Med1993; 9: 95–126.
8.
UttenthalLOUkponmwanOOWoodSMLong-term effects of intestinal alpha-glucosidase inhibition on postprandial glucose, pancreatic and gut hormone responses and fasting serum lipids in diabetics on sulfonylureas. Diabet Med1986; 3: 155–160.
9.
ConiffRFShapiroJASeatonTBA double-blind placebo-controlled trial evaluating the safety and efficacy of acarbose for the treatment of patients with insulin-requiring type II diabetes. Diabetes Care1995; 18: 928–932.
10.
KanekoTSuzukiNInoueKClinical evaluation of combined therapy with an insulin sensitizer, AD4833 and voglibose in type 2 diabetes patients – a non-blind, phase III study (in Japanese). Jap J Clin Exp Med1997; 74: 1540–1556.
11.
AkanumaYKosakaKKuzuyaTLong-term study of a new oral hypoglycaemic drug CS-045 in patients with non-insulin dependent diabetes mellitus (in Japanese, English abstract). J Clin Ther Med1993: 9 (Suppl 3): 119–141.
12.
CarrascosaMPascualFArestiSAcarbose-induced acute severe hepatotoxity. Lancet1997; 349: 698–699.
13.
KuramotoTShimizuNTodaGLiver dysfunction associated with troglitazone (Noscal) (in Japanese, English abstract). J Clin Ther Med1998; 14: 461–466.
14.
FukudaMClinical arrangement of classification of diabetic retinopathy. Tohoku J Exp Med1983; 141 (Suppl): 331–335.
15.
MatthewsDRHoskerJPHomeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in men. Diabetologia1985; 28: 412–419.
16.
OdakaHSatohYAmanoN Antidiabetic actions of insulin sensitizer alone or in combination with α-glucosidase inhibitor in genetically obese-diabetic rats, Wistar fatty (in Japanese, English abstract). Jpn Pharmacol Ther1997; 25: 355–361.
17.
FujiwaraTYoshidaSYoshiokaTCharacterization of a new oral antidiabetic agent CS-045: studies in KK and ob/ob mice and Zucker fatty rats. Diabetes1988; 37: 1549–1558.
18.
SuterSLNolanJJWallacePMetabolic effects of new oral hypoglycaemic agent CS-045 in NIDDM patients. Diabetes Care1992; 15: 193–203.
19.
FujiwaraTYoshiokaSYoshiokaTCharacterization of new oral antidiabetic agent CS – 045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes1988; 37: 1549–1558.
20.
PicardFDeshaiesYPostprandial serum lipids and lipoprotein lipase are acutely altered in rats by the alpha-glucosidase inhibitor acarbose. Horm Metab Res1996; 28: 377–380.
21.
DavidsonJCohnJSTriglycerides: a risk factor for coronary heart disease. Atherosclerosis1996; 124: S57 – S64.
22.
ChiassonJLThe effect of acarbose on insulin sensitivity in patients with impaired glucose tolerance. Diabet Med1996; 13: S23 – S24.
23.
ChawlaASchwarzEJDimaculanganDDPeroxisome proliferatoractivated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology1994; 135: 798–800.
24.
LehmannJMMooreLBSmith-OliverTAAn antidiabetic thiazolidione is a high affinity ligand for peroxisome proliferative activated receptor-gamma (PPAR gamma). J Biol Chem1995; 270: 12953–12956.
25.
InoueITakahashiKKatayamaSEffect of troglitazone (CS-045) and bezafibrate on glucose tolerance, fiver glycogen synthase activity, and β-oxidation in fructose-fed rats. Metabolism1995; 44: 1626–1630.
26.
HallukouSDoareLFoufelleF Pioglitazone induces in vivo adipocytes differentiation in the obese Zucker fa/fa rat. Diabetes1997; 46: 1393–1399.
27.
OkunoATamemotoHTobeKTroglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest1998; 101: 1354–1361.
