Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pioglitazone (Actos-Takeda) and rosiglitazone (Avandia-GlaxoSmithKline) belong to a new class of oral antidiabetic medicines (the glitazones or thiazolidinediones). Both are licensed in the UK for "oral combination treatment of type 2 diabetes mellitus in [narrowly defined groups of] patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea". They are not licensed for use as monotherapy, in combination with insulin, or as part of triple therapy with metformin or a sulphonylurea. What can pioglitazone and rosiglitazone offer in the management of patients with type 2 diabetes?
 ...
PMID:Pioglitazone and rosiglitazone for diabetes. 1158 2

Rosiglitazone (Avandia, Glaxo-SmithKline) belongs to a new family of oral hypoglycaemic agents, thiazolidinediones or glitazones. These molecules act as selective agonists of nuclear receptors (PPAR gamma) and improve insulin sensitivity. In Belgium as in all European countries, rosiglitazone is indicated for the treatment of type 2 diabetes, only in combination with another antidiabetic oral agent, in patients insufficiently controlled with metformin or a sulphonylurea at a maximal tolerated dose. In these patients, rosiglitazone, at a daily dose of 4 mg (sometimes 8 mg/day with metformin), reduces fasting glycaemia by 2-3 mmol/l and glycated haemoglobin level by about 1%. It exerts also favourable effects on some risk factors related to insulin resistance syndrome, which may contribute to improve cardiovascular prognosis of patients with type 2 diabetes. Hepatic safety of rosiglitazone seems to be good, although it is still recommended to check liver enzymes regularly. As all glitazones, rosiglitazone moderately promotes weight gain. It can also induce some fluid retention which may reveal or aggravate heart failure in at risk patients.
 ...
PMID:[Medication of the month. Rosiglitazone (Avandia)]. 1207 98

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and gamma-glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.
 ...
PMID:Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. 1214 28

Rosiglitazone (CAS 155141-29-0, Avandia) is a novel insulin sensitizer used in the treatment of type 2 diabetes. A sensitive high performance liquid chromatography (HPLC) method for its determination in human plasma using fluorescence detection (excitation: 247 nm, emission: 367 nm) with a suitable internal standard (I. S.) is described. Ethyl acetate was used as extraction solvent. A mobile phase consisting of phosphate buffer, acetonitrile and methanol was used at a flow rate of 1.0 ml/min on a C18 column. The absolute recovery was > 90% and the lower limit of quantitation was 5 ng/ml. The intra- and inter-day relative standard deviations ranged from 0.58-6.69% and 0.82-6.63%, respectively. The method described is simple, economical, precise and accurate and has been successfully applied in a pharmacokinetic study conducted in healthy human volunteers.
 ...
PMID:HPLC method for the determination of rosiglitazone in human plasma and its application in a clinical pharmacokinetic study. 1218 80

This was an open-label, randomised 26-week study to determine the effects of adding 4 mg rosiglitazone (Avandia) daily to existing sulphonylurea (SU) therapy in patients with type 2 diabetes from India, Brazil, The Philippines, Thailand, Argentina and Tunisia. Of the 348 patients, 175 received 2 mg rosiglitazone twice daily plus SU (RSG+SU) and 173 received SU alone (at their normal dose). The RSG+SU group showed a significant reduction in HbA1c (mean HbA1c 9.05% at baseline, 7.92% at 26 weeks, mean change -1.13 (95% Cl -1.37, -0.89)). Mean HbA1c essentially remained unchanged in the control group (8.9 to 9.0%). The RSG+SU group showed a significant decrease in fasting plasma glucose concentration (FPG) (mean FPG 198.7 mg/dl at baseline, 160.3 mg/dl at 26 weeks, mean change -38.4 (95% Cl -47.1, -29.7)) while the controls showed a non-significant increase from 194 to 200 mg/dl. Significantly more patients in the RSG+SU group achieved FPG < 140 mg/dl, > or = 0.7% decrease in HbA1c, and > or = 30 mg/dl decrease in FPG between baseline and week 26 than the controls (p = 0.0001 in each case). Adverse events were similar in both groups; more patients in the RSG+SU group reported hypoglycaemia, but most cases were mild. This study shows that adding rosiglitazone to existing SU treatment improves glycaemic control and is well-tolerated in patients with type 2 diabetes from a wide range of non-Western countries.
 ...
PMID:An international study of the effects of rosiglitazone plus sulphonylurea in patients with type 2 diabetes. 1256 55

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR-gamma receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation. The thiazolidinedione rosiglitazone (Avandia) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, that was recently approved by the Food and Drug Administration for treatment of type II diabetes mellitus. In the present study, we have investigated the effects of rosiglitazone in animal models of acute inflammation (carrageenan-induced paw oedema and carrageenan-induced pleurisy). We report here for the first time that rosiglitazone (given at 1, 3 or 10 mg/kg i.p. concomitantly with carrageenan injection in the paw oedema model, or at 3, 10 or 30 mg/kg i.p. 15 min before carrageenan administration in the pleurisy model) exerts potent anti-inflammatory effects (e.g. inhibition of paw oedema, pleural exudate formation, mononuclear cell infiltration and histological injury) in vivo. Furthermore, rosiglitazone reduced: (1) the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase (PARP), (2) the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the lungs of carrageenan-treated rats. In order to elucidate whether the protective effect of rosiglitazone is related to activation of the PPAR-gamma receptor, we also investigated the effect of a PPAR-gamma antagonist, bisphenol A diglycidyl ether (BADGE), on the protective effects of rosiglitazone. BADGE (30 mg/kg i.p.) administered 30 min prior to treatment with rosiglitazone significantly antagonized the effect of the PPAR-gamma agonist and thus abolished the anti-inflammatory effects of rosiglitazone. We propose that rosiglitazone and other potent PPAR-gamma agonists may be useful in the therapy of inflammation.
 ...
PMID:Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation. 1470 29

Many patients with type 2 diabetes require treatment with more than one antihyperglycemic drug to achieve optimal glycemic control. The thiazolidinediones are a novel class of oral antihyperglycemic drugs that improve glycemic control primarily by increasing peripheral insulin resistance and sensitizing the skeletal muscle, liver and adipose tissue to the actions of insulin, in addition to improving beta-cell function. One of the many features of the thiazolidinedione class of drugs is their synergism with other antihyperglycemic drugs that have a different mechanism of action. The combination of metformin hydrochloride, a biguanide that enhances glucose uptake in peripheral tissues and reduces hepatic gluconeogenesis, with rosiglitazone maleate, one of the newly available members of the thiazolidinedione family, offers a rational therapeutic approach to the treatment of type 2 diabetes. In patients whose type 2 diabetes is inadequately controlled with metformin monotherapy, the addition of rosiglitazone significantly improves glycemic control, insulin sensitivity and beta-cell function, compared with either drug alone. In addition, this combination therapy has beneficial effects on other cardiovascular risk factors. Rosiglitazone maleate/metformin hydrochloride combination therapy is well tolerated in patients with type 2 diabetes and has a favorable safety profile. This review summarizes the available evidence on the clinical efficacy and safety of rosiglitazone maleate and metformin hydrochloride combination therapy in patients with type 2 diabetes.
 ...
PMID:Rosiglitazone maleate/metformin hydrochloride: a new formulation therapy for type 2 diabetes. 1551 Feb 36

A descriptive chart analyses was conducted of 100 consecutive patients at an adolescent medicine clinic at West Virginia University School of Medicine between April and May 2002 to determine the prevalence of overweight and obesity, acanthosis nigricans and hyperinsulinemia. Height, weight, body mass index (BMI), blood pressure, and screening for acanthosis nigricans (AN) were recorded. For patients with AN, fasting lipid, glucose, and insulin levels were also recorded. A total of 37% (37/100) of adolescents were found to be significantly overweight or obese, with BMIs greater than the 85th percentile for gender and age, 28% (28/100) had a BMI greater than the 95th percentile for gender and age, and 17% (17/100) were observed to have AN. In this cohort, 94% (16/17) had a BMI greater than the 95th percentile. Patients with AN were found to have higher mean BMI (39.7 vs. 29.7), systolic (132 vs. 122), and diastolic (73 vs. 65) blood pressures that the patients who were obese and did not have AN. In addition, 16 of the 17 adolescents with AN were found to have elevated fasting insulin levels (mean 33.6). A fasting insulin level was not obtained on a 12-year-old girl with AN already receiving treatment with rosiglitazone (Avandia) for type 2 diabetes mellitus. The prevalence of overweight and obesity in patients at the adolescent clinic is over twice the national average. The prevalence of acanthosis nigricans in this mostly non-minority population is over three times the highest previously reported rate for Caucasians.
 ...
PMID:Prevalence of obesity, acanthosis nigricans and hyperinsulinemia in an adolescent clinic. 1616 28

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione family are used for the treatment of type 2 diabetes mellitus due to their ability to reduce glucose and lipid levels in patients with this disease. Three thiazolidinediones that were approved for treatment are Rezulin (troglitazone), Avandia (rosiglitazone), and Actos (pioglitazone). Troglitazone was withdrawn from the market due to idiosyncratic drug toxicity. Rosiglitazone and pioglitazone are still on the market for the treatment of type 2 diabetes. The authors present data from a gene expression screen that compares the impact these three compounds have in rats, in rat hepatocytes, and in the clone 9 rat liver cell line. The authors monitored the changes in expression in multiple genes, including those related to xenobiotic metabolism, proliferation, DNA damage, oxidative stress, apoptosis, and inflammation. Compared to the other two compounds, troglitazone had a significant impact on many of the pathways monitored in vitro although no major perturbation was detected in vivo. The changes detected predict not only general toxicity but potential mechanisms of toxicity. Based on gene expression analysis, the authors propose there is not just one but multiple ways troglitazone could be toxic, depending on a patient's environment and genetic makeup, including immune response-related toxicity.
 ...
PMID:Gene expression analysis of troglitazone reveals its impact on multiple pathways in cell culture: a case for in vitro platforms combined with gene expression analysis for early (idiosyncratic) toxicity screening. 1659 47

Rosiglitazone is one of the members in the thiazolidinedione (TZD) class of anti-diabetic agents that have proven efficacy in the treatment of patients with type 2 diabetes. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to rosiglitazone maleate (Avandia) and proposed the mechanisms for rosiglitazone-induced thrombocytopenia. Tested by flow cytometry, the patient's serum was positive for rosiglitazone-induced antibody with the binding ratio of 5.93 (mean fluorescence intensity, MFI) in the presence of the patient's serum and rosiglitazone in a final concentration of 0.53 mmol/l. The antibody was found to bind both glycoprotein (GP) IIb-IIIa complex and GP Ib/IX complex by MAIPA assay using five different monoclonal antibodies (mAbs) against GP complexes Ib/IX, GPIIb/IIIa or GPIa/IIa. Immunoprecipitation studies showed that both GPIIb/IIIa and GP Ib/IX complex were precipitated by antibody in the presence, but not in the absence of rosiglitazone. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidiabetic agent rosiglitazone maleate. This report documents the first case of rosiglitazone-induced immune thrombocytopenia.
 ...
PMID:Rosiglitazone-induced immune thrombocytopenia. 1712 88


1 2 Next >>