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At least 595 records · Page 33Linked to original sources
PubMed2001

Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up.

BACKGROUND: A sulfonylurea--usually glyburide--plus metformin constitute the most widely used oral antihyperglycemic combination in clinical practice. Both medications present undesirable cardiovascular effects. The issue whether the adverse effects of each of these pharmacologic agents may be additive and detrimental to the prognosis for coronary patients has not yet been specifically addressed. HYPOTHESIS: This study was designed to examine the survival in type 2 diabetics with proven coronary artery disease (CAD) receiving a combined glyburide/metformin antihyperglycemic treatment over a long-term follow-up period. METHODS: The study sample comprised 2,275 diabetic patients, aged 45-74 years, with proven CAD, who were screened but not included in the bezafibrate infarction prevention study. In addition, 9,047 nondiabetic patients with CAD represented a reference group. Diabetics were divided into four groups on the basis of their therapeutic regimen: diet alone (n = 990), glyburide (n = 953), metformin (n = 79), and a combination of the latter two (n = 253). RESULTS: The diabetic groups presented similar clinical characteristics upon recruitment. Crude mortality rate after a 7.7-year follow-up was lower in nondiabetics (14 vs. 31.6%, p<0.001). Among diabetics, 720 patients died: 260 on diet (mortality 26.3%), 324 on glyburide (34%), 25 on metformin alone (31.6%), and 111 patients (43.9%) on combined treatment (p<0.000001). Time-related mortality was almost equal for patients on metformin and on combined therapy over an intermediate follow-up period of 4 years (survival rates 0.80 and 0.79, respectively). The group on combined treatment presented the worst prognosis over the long-term follow-up, with a time-related survival rate of 0.59 after 7 years, versus 0.68 and 0.70 for glyburide and metformin, respectively. After adjustment to variables for prognosis, the use of the combined treatment was associated with an increased hazard ratio (HR) for all-cause mortality of 1.53 (95% confidence interval [CI] 1.20-1.96), whereas glyburide and metformin alone yielded HR 1.22 (95% CI 1.02-1.45) and HR 1.26 (95% CI 0.81-1.96), respectively. CONCLUSIONS: We conclude that after a 7.7-year follow-up, monotherapy with either glyburide or metformin in diabetic patients with CAD yielded a similar outcome and was associated with a modest increase in mortality. However, time-related mortality was markedly increased when a combined glyburide/metformin treatment was used.

Administration, Oral↗
PubMed2004

Scoparia dulcis, a traditional antidiabetic plant, protects against streptozotocin induced oxidative stress and apoptosis in vitro and in vivo.

Oxidative stress is implicated in the pathogenesis of diabetic complications. The experiments were performed on normal and experimental male Wistar rats treated with Scoparia dulcis plant extract (SPEt). The effect of SPEt was tested on streptozotocin (STZ) treated Rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. Administration of an aqueous extract of Scoparia dulcis by intragastric intubation (po) at a dose of 200 mg/kg body weight significantly decreased the blood glucose and lipid peroxidative marker thiobarbituric acid reactive substances (TBARS) with significant increase in the activities of plasma insulin, pancreatic superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in streptozotocin diabetic rats at the end of 15 days treatment. Streptozotocin at a dose of 10 mug/mL evoked 6-fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. The extract markedly reduced the STZ-induced lipidperoxidation in RINm5F cells. Further, SPEt protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. Treatment of RINm5F cells with 5 mM STZ and 10 mug of SPEt completely abrogated apoptosis induced by STZ, suggesting the involvement of oxidative stress. Flow cytometric assessment on the level of intracellular peroxides using fluorescent probe 2'7'-dichlorofluorescein diacetate (DCF-DA) confirmed that STZ (46%) induced an intracellular oxidative stress in RINm5F cells, which was suppressed by SPEt (21%). In addition, SPEt also reduced (33%) the STZ-induced apoptosis (72%) in RINm5F cells indicating the mode of protection of SPEt on RIN m5Fcells, islets, and pancreatic beta-cell mass (histopathological observations). Present study thus confirms antihyperglycemic effect of SPEt and also demonstrated the consistently strong antioxidant properties of Scoparia dulcis used in the traditional medicine.

Animals↗
PubMed2006

Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an antidiabetic and lipid-lowering drug, after oral administration of its hydroxypropyl-beta-cyclodextrin complex to bile duct-cannulated rats.

The effect of bile acids on bioavailability of FPFS-410 (2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine) after oral administration of the drug and its 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) complex was investigated. The complexation with HP-beta-CyD increased the oral bioavailability of FPFS-410 in normal rats in a HP-beta-CyD concentration-dependent manner, compared with that of drug alone. In bile duct-cannulated rats, bile acid concentrations in pylic serum and biliary were decreased to 18% and 14% of sham-operated rats, respectively. After oral administration of the HP-beta-CyD complex, the plasma levels of FPFS-410 were lower in bile duct-cannulated rats than in sham-operated rats up to 1 h, however, this order reversed from 2 to 12 h. The plasma levels of M1, a dominant metabolite of FPFS-410 in rats, significantly decreased until 2 h after administration of the complex in bile duct-cannulated rats, compared with in sham-operated rats. Bioconversion of FPFS-410 to M1 and CYP3A2 expression in the liver was markedly lowered by bile duct-cannulation. Bile duct-cannulation did not, however, affect the serum levels of estradiol. These results suggest that bile acids have a pivotal role for bioavailability of FPFS-410 after oral administration of the FPFS-410 complex with HP-beta-CyD through CYP3A2 activity in liver of rats.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1987

Preparation and antidiabetic activity of new substituted 3,5-diarylpyrazolesulfonylurea derivatives. II: Structure-activity relationship.

Four series of substituted p-(3,5-diaryl-2-pyrazoline-1) benzenesulfonylurea and thiourea derivatives, along with their corresponding substituted p-(3,5-diarylpyrazole-1) benzenesulfonylurea and thiourea derivatives, were prepared for evaluation as hypoglycemic agents. Preliminary biological testing revealed that the new compounds possess potent hypoglycemic activity.

Alloxan↗
PubMed2005

Trends and influences on use of antidiabetic drugs in England, 1992-2003.

OBJECTIVE: To describe trends in prescribing for glycaemic control in diabetes mellitus in England, 1993-2003, and to examine the effects of new clinical evidence or national guidance on these. DESIGN: Observational study of prescribing adjusted for extrapolated changes in epidemiology of insulin and non-insulin treated diabetes. SETTING: Primary care in England, 1992-2003. DATA SOURCES: Three monthly prescribing data from the Prescription Pricing Authority. MAIN OUTCOME MEASURES: Defined daily doses/patient/quarter of oral hypoglycaemics and of insulin. RESULTS: There was an increase in the prevalence of both insulin treated (85%) and non-insulin treated (80%) diabetes. There were increases in all drug use, which were largely explained by this: for example, sulphonylurea use increased by 101% in total but only 11% after correction for change in prevalence and population; insulin use increased by 140% in total, but 33% after correction. Neither guidances from the National Institute of Clinical Excellence nor new clinical evidence had any discernible effect on this. An exception was metformin use, which increased by 495% in total, and by 277% after correction. This increase occurred mainly from early 1998 and seemed to coincide with the publication of evidence of the specific benefits of metformin. CONCLUSIONS: There has been a trend towards more aggressive treatment of diabetes. National guidance may have reinforced this but has not altered the trend. Specific evidence around metformin may have been very influential in increasing its use.

Diabetes Mellitus↗