SEARCH · PubMed Health

Results for “Glyburide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1991

Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide.

In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies.

Adult↗

PubMed1990

Effect of glyburide on beta cell responsiveness to glucose in non-insulin-dependent diabetes mellitus.

Since the introduction of glyburide in 1984, many studies have evaluated the effects of this oral hypoglycemic agent on beta cell function in patients with non-insulin-dependent diabetes mellitus. The early studies, which were performed in patients receiving concomitant insulin therapy, may have underestimated the true effect of glyburide on insulin secretion. The more recent studies demonstrate that both short- and long-term glyburide therapy increase C-peptide levels in diabetic as well as nondiabetic subjects and that the effects of glyburide are comparable to those of the other second-generation sulfonylurea, glipizide. The effects of glyburide on insulin secretory rates calculated from plasma C-peptide levels were recently evaluated using individually derived C-peptide kinetic parameters and a validated open two-compartment model of peripheral C-peptide kinetics. Glyburide did not influence fasting insulin secretion (196 +/- 34 versus 216 +/- 23 pmol/min) but did cause an increase in the total amount of insulin secreted over a 24-hour period (447 +/- 58 versus 561 +/- 55 nmol). This increase in the production of insulin was generated by an increase in amplitude of secretory pulses occurring after lunch and dinner rather than by a greater number of pulses. The full effect of glyburide on the beta cell became evident when glucose concentrations were clamped at the hyperglycemic level of 300 mg/dL both before and during treatment for a 3-hour period. During that time, insulin secretion rates increased by 221 percent in response to glyburide. Glyburide did not, however, completely reverse the beta cell secretory defect characteristic of non-insulin-dependent diabetes mellitus. In the patients receiving glyburide, the sluggish insulin secretory response to breakfast persisted, and the insulin secretory response during the hyperglycemic clamping was less than the response normally seen in nondiabetic subjects. These experiments suggest that the primary effect of glyburide on the beta cell is to increase its responsiveness to glucose. Although the precise mechanism of action of glyburide at the cellular level is unclear, in vitro studies suggest that its effect is mediated through binding with specific receptors on the beta cell membrane, which in turn leads to alterations in the cellular efflux of potassium ions and influx of calcium ions.

C-Peptide↗

PubMed1992

Glyburide and tolbutamide induce desensitization of insulin release in rat pancreatic islets by different mechanisms.

Insulin secretion was studied in rat pancreatic islets after 24-h exposure to various glyburide or tolbutamide concentrations. Glucose-induced insulin release was significantly (P < 0.05) reduced in islets cultured with 0.1 microM glyburide or 100 microM tolbutamide (2098 +/- 187, 832 +/- 93, and 989 +/- 88 pg/islet.h in control, glyburide-exposed, and tolbutamide-exposed islets, respectively). When glyburide-treated islets were stimulated with glyburide or tolbutamide, insulin release was also impaired compared to that in control islets (P < 0.05). In contrast, tolbutamide-exposed islets showed an impaired response to tolbutamide, but a normal response to glyburide. To investigate the mechanism of the sulfonylurea-induced impairment of insulin secretion, we measured insulin release and Rb+ efflux (a marker of the K+ channel activity) in a perifusion system and islet Ca2+ uptake under static conditions. Insulin release in response to 16.7 mM glucose increased in control islets from 9.4 +/- 1.1 to 131 +/- 19 pg/islet.min (first phase secretion peak). Simultaneously, the fractional 86Rb+ efflux declined from 0.015 +/- 0.002% to 0.006 +/- 0.001% (change in decrement, -63.5%). Glucose-induced insulin release in glyburide- and tolbutamide-treated islets was significantly reduced (first phase peak, 22.1 +/- 5 and 39.7 +/- 8 pg/islet.min, respectively; P < 0.05), and the fractional 86Rb+ efflux decrement was -21 +/- 6% for glyburide (P < 0.005 vs. control islets) and -65 +/- 4% (not different from control) for tolbutamide. When glyburide- or tolbutamide-exposed islets were stimulated with the corresponding sulfonylurea, insulin release was impaired compared to that in control islets (P < 0.05), but, again, 86Rb+ efflux was impaired (P < 0.05) only in glyburide-exposed islets. When 45Ca2+ uptake was studied, the increase in glucose concentration from 2.8 to 16.7 mM increased calcium uptake in control islets from 1.76 +/- 0.58 to 7.27 +/- 1.36 pmol/islet.2 min (n = 4). Preexposure to 0.1 microM glyburide did not change calcium uptake at a glucose concentration of 2.8 mM (1.44 +/- 0.45 pmol/islet.2 min) but significantly reduced calcium uptake stimulated by 16.7 mM glucose (3.21 +/- 0.35 pmol/islet.2 min; n = 4; P < 0.005 compared to control islets). In contrast, preexposure to 100 microM tolbutamide did not change either basal or glucose-stimulated calcium uptake (1.44 +/- 0.45 and 6.90 +/- 0.81 pmol/islet.2 min, respectively; n = 4). These data show that in vitro chronic exposure of pancreatic islets to the sulfonylureas glyburide and tolbutamide impairs their ability to respond to a subsequent glucose or sulfonylurea stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Evaluation of a potential interaction between erythromycin and glyburide in diabetic volunteers.

The effects of erythromycin on the pharmacokinetics and pharmacodynamics of glyburide were evaluated in 12 patients with non-insulin-dependent diabetes mellitus (fasting blood glucose levels 140-280 mg/dL), who received 4 days of treatment with erythromycin base (333 mg administered orally every 8 hr) and a control treatment in a randomized crossover design; 5 mg glyburide was administered on day 4 of each study period. Serum glyburide concentrations were determined by high-performance liquid chromatography. Peak serum glyburide concentrations were increased by 18%, and mean time to peak glyburide concentrations (Tmax) decreased from 4.9 to 3.0 hours during erythromycin treatment; only the difference in Tmax was statistically significant. No significant effects on glyburide clearance were observed. No significant differences in glucose clearance after carbohydrate loads were observed between erythromycin + glyburide and glyburide treatments. These data show that oral erythromycin base treatment does not affect glyburide metabolism but does affect the rate of glyburide absorption. This effect may be mediated by the stimulation of gastric motility by erythromycin. The clinical significance of the effects of erythromycin on glyburide kinetics appears to be minimal, based on the determinations of serum glucose concentrations.

Adult↗

PubMed1992

Evaluation of glipizide and glyburide in a health maintenance organization.

OBJECTIVE: To determine if there was a difference in the long-term glycemic control, average daily dose, and cost of therapy in patients with noninsulin-dependent diabetes mellitus (NIDDM) treated with glyburide and glipizide in a health maintenance organization (HMO). DESIGN: Retrospective evaluation of medical and pharmacy records. SETTING: Multispecialty group practice HMO. PATIENTS: 140 NIDDM patients being treated with either glyburide (n = 70) or glipizide (n = 70) were randomly selected from the populations of patients receiving either drug using computerized pharmacy records. MAIN OUTCOME MEASURE: Mean daily doses and blood glucose measurements (fasting blood glucose, random blood glucose, hemoglobin A1C) were stratified in 3-month periods from the time the drug therapy was started or the patient first presented to the clinic for a total of 18 months. Long-term glycemic control was defined as fasting blood glucose less than 8.33 mmol/L (150 mg/dL). RESULTS: The groups were comparable with regard to age (53.4 y glyburide, 56.7 y glipizide), gender (43 M:27 F glyburide, 47 M:23 F glipizide), race (38 W/16 B/16 H glyburide, 45 W/16 B/9 H glipizide), concurrent medical conditions, adverse effects, and compliance. Long-term glycemic control was similar in both groups. Although the number of subjects who were controlled (by definition) tended to be greater in the glyburide group, no clinical or statistical difference was found. There was no statistical difference in mean daily dose between the ethnic groups, but the small numbers preclude further analysis. The glipizide group had a larger percentage increase in dose within the first year than did the glyburide group; however, the percentage increase from the 3-month dose was similar after 18 months (22.7 percent glyburide, 27.5 percent glipizide.) Average daily cost of therapy, based on mean daily dose, was slightly lower for glyburide-treated patients. CONCLUSIONS: If glycemic control is similar with glyburide and glipizide, as seen in this study, economic considerations regarding choice of therapy and formulary inclusion may be appropriate.

Adult↗

PubMed1991

Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis.

To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C]-glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5-isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

Pharmacokinetics and pharmacodynamics of glyburide in young and elderly nondiabetic adults.

The pharmacokinetics and pharmacodynamics of glyburide were studied in elderly and young nondiabetic adults. Healthy nondiabetic men and women 18-40 years of age (young subjects) and 60-85 years of age (elderly subjects) were recruited. After an overnight fast, the subjects were given a baseline glucose tolerance test (GTT). The next day, again after a fast, each subject was given a 5-mg oral tablet of glyburide, and the GTT was performed one hour later. Serum glucose, serum insulin, and plasma glyburide concentrations were determined. Twenty elderly (mean +/- S.D. age, 65.7 +/- 5.3 years) male (n = 10) and female (n = 10) volunteers and 15 young (22.3 +/- 4.5 years) male volunteers were enrolled. Compared with the young subjects, the elderly subjects had slower glyburide absorption, as determined from a lower peak plasma concentration and smaller area under the plasma concentration-time curve from zero to four hours (AUC0-4). The elderly subjects also had a lower glyburide elimination rate constant and higher volume of distribution and a 52% higher free fraction. There was no difference in the glyburide AUC0-24 or AUC0-infinity or in oral clearance between the groups. The elderly group had greater increases in serum glucose and insulin concentrations after the baseline GTT. After glyburide administration, the elderly group had a smaller fractional decrease in the glucose AUC0-3 from the baseline GTT result than the young subjects. Linear regression analysis of the relationship between the fractional change in glucose concentration and the glyburide AUC0-4 showed significantly different slopes between the two groups. The aging process appears to affect the pharmacokinetics and pharmacodynamics of glyburide.

Adolescent↗

PubMed1990

Effects of glyburide on in vivo insulin-mediated glucose disposal.

The purpose of this study was to examine the effects of glyburide on peripheral (muscle) and hepatic insulin sensitivity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) as well as in healthy control subjects. In protocol 1, 10 patients with NIDDM and seven young healthy control subjects were studied. Changes in insulin sensitivity (40 mU/m2.min euglycemic insulin clamp), hepatic glucose production (3-[3H]glucose turnover), and insulin secretion (+125 mg/dL hyperglycemic clamp) were measured before and after 3 months (in patients with NIDDM) and 6 weeks (in young control subjects) of glyburide therapy. In protocol 2, five patients with IDDM and eight patients with insulin-treated NIDDM were evaluated before and after two months of glyburide therapy (20 mg per day). Changes in daily insulin requirements, 24-hour plasma glucose profiles, glycohemoglobin, glucagon-stimulated C-peptide secretion, insulin sensitivity, and hepatic glucose production were measured. In protocol 1, glyburide significantly improved insulin sensitivity (p less than 0.01) and insulin secretion (p less than 0.01) in the NIDDM patients. The elevated rates of hepatic glucose production (2.4 +/- 0.3 mg/kg.min) were reduced after glyburide therapy (1.7 +/- 0.2 mg/kg.min; p less than 0.01) and were highly correlated with an improvement in fasted plasma glucose levels (r = 0.92; p less than 0.001). Insulin sensitivity also improved in the young healthy control subjects after glyburide therapy (6.5 +/- 0.5 to 7.6 +/- 0.7 mg/kg.min; p less than 0.05). In protocol 2, glyburide treatment produced no change in daily insulin requirement (54 +/- 8 versus 53 +/- 7 units per day), mean 24-hour glucose levels (177 +/- 20 versus 174 +/- 29 mg/dL), glycohemoglobin (10.1 +/- 1.0 percent versus 9.5 +/- 7 percent), C-peptide secretion, insulin sensitivity, or basal hepatic glucose production (p values not significant) in the IDDM patients. In contrast, the insulin-treated NIDDM patients had significant reductions in mean daily insulin requirement (72 +/- 6 versus 58 +/- 9 units per day; p = 0.05), mean 24-hour plasma glucose levels (153 +/- 10 to 131 +/- 5 mg/dL; p less than 0.05), and glycohemoglobin levels (10.3 +/- 0.7 percent to 8.0 +/- 0.4 percent; p less than 0.05) and an improvement in C-peptide secretion (0.24 +/- 0.07 to 0.44 +/- 0.09 pmol/mL; p = 0.08). Stimulated C-peptide levels were highly correlated with a reduction in insulin dose observed during the 2-month treatment period (r = 0.93; p less than 0.001). Insulin sensitivity improved slightly but not significantly after glyburide treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Treatment of type I diabetes with a combination of glyburide and insulin.

OBJECTIVE: To assess the ability of a combination of insulin and an oral hypoglycemic agent (glyburide) to improve the overall glycemic control in a population of patients with type I diabetes. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Community-based, university-affiliated, family medicine group. PATIENTS: Men and women between 18 and 68 years of age with type I diabetes. INTERVENTIONS: Subjects were observed and titrated on an insulin-only regimen for 12 weeks (phase I). Subjects were then randomized to receive either placebo or glyburide 10 mg/d for an additional 12 weeks (phase II). MAIN OUTCOME MEASURES: Glucose measurements were taken at breakfast, lunch, supper, and bedtime. Each patient also was followed sequentially for serum lipids, glycosylated hemoglobin, (Hb A1c) and daily insulin utilization. RESULTS: Average fasting blood glucose (FBG) measurements were significantly lower in the glyburide-treated group during phase II (9.22 +/- 0.55 mmol/L) compared with baseline (10.27 +/- 0.93 mmol/L) and phase I (10.41 +/- 0.55 mmol/L). A decrease in the average Hb A1c concentration in the glyburide group was evident by week 4 and was sustained for the duration of the study. The average daily insulin dose rose significantly in the glyburide but not the placebo group compared with baseline. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change significantly in either group over the course of the study. High-density lipoprotein cholesterol increased significantly over baseline in the glyburide group during phase II. Several patients experienced dramatic improvements in glycemic parameters after the addition of glyburide to their insulin regimens. CONCLUSIONS: Improvements were observed in the FBG and Hb A1c measurements of this heterogeneous population of patients with type I diabetes after the addition of glyburide to their insulin regimens. The study failed to find consistent trends in glycemic control when evaluating mean changes in FBG measurements.

Adolescent↗

PubMed1990

An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide.

Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.

Adult↗

PubMed1990

Effect of glyburide on hepatic glucose metabolism.

Glyburide, along with the other second-generation oral hypoglycemic agent glipizide, has been used as adjunctive therapy for the treatment of non-insulin-dependent diabetes mellitus. After glyburide therapy, basal glycemia and glucose response to a meal are greatly improved. The mechanism for the glucose-lowering effect of the drug remains controversial. Glyburide is generally thought to exert two major actions: stimulation of pancreatic insulin secretion and enhancement of insulin action in hepatic and extrahepatic tissues. Studies in patients with non-insulin-dependent diabetes mellitus indicate that the action of glyburide on the liver plays a central role in decreasing glucose. With short-term therapy, glyburide decreases hepatic glucose production by elevating pancreatic insulin secretion. However, this increase in pancreatic insulin secretion is not sustained as therapy is continued, suggesting that glyburide then acts directly on the liver. The mechanism for the improvement in hepatic glucose metabolism after long-term treatment is not known. In vitro, glyburide has been shown to inhibit gluconeogenesis as well as glycogenolysis and to enhance hepatic glucose uptake, thus providing possible explanations for the action of the drug on the liver.

Diabetes Mellitus, Type 2↗

PubMed1991

Glyburide priming of beta cells. Possible involvement of phosphoinositide hydrolysis.

In the simultaneous presence of 5.5 mM glucose, exposure of isolated perifused islets to the sulfonylurea glyburide (500 nM) acutely stimulated insulin release and amplified the subsequent insulin secretory responses to 10 mM glucose or 10 mM arginine. This sensitizing effect of glyburide developed within 10 min, was maintained for at least 40 min after glyburide removal from the perifusion medium, and was attenuated by the calcium channel blocker nitrendipine. In islets whose inositol-containing lipids were prelabeled during a 2-hr incubation period with myo[2-3H]inositol, glyburide induced a concentration-dependent increase in labeled inositol phosphate accumulation. Nitrendipine abolished this stimulatory effect of glyburide. In perifused islets, the stimulatory effect of glyburide on phosphoinositide (PI) hydrolysis persisted after its removal from the medium and the duration of this effect paralleled the duration of sensitization. These findings suggest that glyburide-induced increases in PI hydrolysis account, at least in part, for its acute stimulatory effect on insulin output and its ability to sensitize islets to subsequent stimulation.

Animals↗

PubMed1992

Coronary reactive hyperemia and adenosine-induced vasodilation are mediated partially by a glyburide-sensitive mechanism.

The effect of glyburide on coronary reactive hyperemia and dilator responses to adenosine was evaluated in isolated perfused guinea pig hearts and anesthetized dogs. In isolated guinea pig hearts, changes in flow due to increasing concentrations of adenosine were measured, followed by 2 min of global ischemia to produce reactive hyperemia. This procedure was repeated after glyburide treatment. A similar study was performed in anesthetized open chest dogs. In isolated guinea pig hearts, 1 microM glyburide reduced reactive hyperemia with a peak flow reduction of 30.7% and debt repayment reduction of 78.0%, relative to vehicle-treated hearts. The adenosine dose-response curve in these hearts was shifted 20-fold to the right by 1 microM glyburide. Glyburide (3 mg/kg + 0.01 mg/kg/min) in dogs inhibited both the peak flow (from 154 +/- 26 to 105 +/- 22 ml/min) and the percentage of debt repayment (from 756 +/- 243 to 336 +/- 88%) of reactive hyperemia. Additionally, the canine intracoronary adenosine response curve was shifted rightward 100-fold by glyburide. Thus, there is a glyburide-sensitive component influencing the magnitude of both the adenosine and the reactive hyperemia response, suggesting that some of this response involves ATP-sensitive potassium channels.

Adenosine↗

PubMed1990

Glyburide increases insulin sensitivity and responsiveness in peripheral tissues of the rat as determined by the glucose clamp technique.

The effect of chronic glyburide treatment on insulin sensitivity and responsiveness in vivo in unanesthetized male Sprague-Dawley rats was determined by the hyperinsulinemic-euglycemic clamp technique. Normal animals were surgically prepared for the clamp procedure and then gavaged with glyburide, 2 mg/kg/day, or with normal saline for 6-18 days. Basal plasma glucose concentrations were significantly lower in glyburide-treated animals compared to controls, but basal plasma insulin concentrations were the same. Rates of glucose disposal, calculated before and during insulin infusions of 2 to 40 mU/kg.min with plasma glucose concentration clamped at 125 mg/dl, were significantly greater in the glyburide-treated rats compared to controls. Insulin dose-response curves demonstrate that glyburide treatment increased both insulin sensitivity and responsiveness. Basal hepatic glucose production, estimated by D-[3-3H]Glucose infusion, was significantly greater with glyburide treatment; however the sensitivity of the liver to suppression by insulin infusions of 2 and 4 mU/kg.min was unchanged. These data suggest that the decreased basal plasma glucose concentration observed in rats chronically treated with glyburide is the result of increased glucose disposal in peripheral tissues and not associated with an increase in plasma insulin concentrations or a decrease in hepatic glucose production.

Animals↗

PubMed1992

Combination therapy for NIDDM with biosynthetic human insulin and glyburide.

OBJECTIVE: TO investigate the effects of the addition of glyburide to the regimen of insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients with regard to their overall insulin requirement and dosage schedule and to assess persistence of these effects. RESEARCH DESIGN AND METHODS: A double-blind randomized parallel-groupo, placebo-controlled, 20-wk outpatient trial at the Clinical Research Unit (CRU) at St. Luke's/Roosevelt Hospital (New York). Subjects were 20 insulin-dependent NIDDM patients previously managed on insulin alone. After a baseline period of satisfactory diabetes control on biosynthetic human insulin alone, insulin dosage was halved, and patients were placed on a combination with either glyburide or placebo. Diabetes control equivalent to baseline was reestablished by adjusting insulin as required on subsequent visits to the CRU. RESULTS: Insulin requirements in the glyburide group decreased by 29 U at 14 wk compared with 9 U in the placebo group (P less than 0.05). At 20 wk, the decreases remained significant (25 vs. 11 U, respectively; P less than 0.05). The mean +/- SD reduction in insulin requirement in the glyburide group was relatively constant (25 +/- 10 U) and was not related to premedication insulin requirement. Successful response to glyburide was inversely correlated with initial serum alkaline phosphatase level. CONCLUSIONS: Glyburide reduces insulin requirements for 20 wk of combination therapy in NIDDM patients. Patients whose initial insulin requirement is less than or equal to 25 U have a 50% chance of achieving equivalent glycemic control on glyburide alone.

Aged↗

PubMed1992

Differential effects of glyburide on premature beats and ventricular tachycardia in an isolated tissue model of ischemia and reperfusion.

Possible anti- and proarrhythmic effects of glyburide, an ATP-sensitive K+ channel blocker, were assessed in an isolated tissue model of reperfusion. Transmembrane electrical activity was recorded from endo- and epicardium of isolated segments of guinea pig right ventricular free walls, or two sites on papillary muscles with microelectrodes. An electrocardiogram was recorded by two electrodes placed at opposite ends of the tissue bath. Regular stimulation was delivered to endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Rapid sustained or nonsustained ventricular tachycardia, bigeminy or trigeminy with characteristics of transmural re-entry occurred early in reperfusion in 50% of free walls. Triggered arrhythmias with characteristics of oscillatory afterpotentials (delayed afterdepolarizations) occurred in 20%. Arrhythmias were accompanied by prolongation of transmural conduction times and abbreviation of endocardial effective refractory periods and action potential durations. Glyburide (3 or 30 microM) significantly attenuated abbreviation of action potential durations and effective refractory periods during ischemic conditions and early reperfusion. Neither endocardial nor transmural conduction times were modified by glyburide; however, glyburide significantly decreased the incidence of transmural conduction block during ischemic conditions. Glyburide abolished reperfusion arrhythmias with characteristics of re-entry, but potentiated oscillatory afterpotentials in papillary muscles and triggered arrhythmias with characteristics of oscillatory afterpotentials in free walls. Identical effects were seen with glyburide present in ischemic solution, or in both ischemic and reperfusion solutions, but no effect was observed with glyburide present only in reperfusion. Our study demonstrates possible cellular mechanisms underlying simultaneous pro- and antiarrhythmic drug effects exerted on late premature beats and rapid arrhythmias and closely coupled premature beats.

Action Potentials↗

PubMed1991

Insignificant transfer of glyburide occurs across the human placenta.

No data exist concerning human placental transfer of oral hypoglycemic agents during pregnancy. This study characterizes the transport of glyburide in 10 term human placentas with the single-cotyledon placental model. Serial samples were taken from both the maternal and fetal reservoirs during each 3-hour perfusion, and the percent transport and metabolism of tritiated glyburide was calculated with liquid scintillation spectrometry and high-performance liquid chromatography. Antipyrine labeled with carbon 14 was added to the perfusate solution during these experiments as a control. Virtually no transfer of glyburide occurred, and no appreciable metabolism of the drug was detected. Neither variation in the albumin concentration nor increase in the maternal glyburide levels to 100 times therapeutic concentration materially altered the rate of transport. These data show that insignificant transport of glyburide occurs across the human placenta in vitro and suggest that fetal exposure to maternally administered glyburide likewise may be insignificant.

Diazepam↗

PubMed1992

Effect of tolbutamide and glyburide on pyruvate kinase flux in isolated rat hepatocytes.

The effects of two representative sulfonylureas, tolbutamide and glyburide, on pyruvate kinase (PK) flux were examined in fasted rat hepatocytes. PK flux was estimated by trapping 14C from NaH14CO3 in a 2 mM lactate pool, accounting for any incomplete trapping by parallel incubations with L-[1-14C]alanine. Glyburide (20 microM) and tolbutamide (1 mM) decreased glucose formation by 34.9% and 54.8%, respectively, from 2 mM lactate. This decrease in glucose formation was associated with a proportional decrease in pyruvate carboxylase (PCOX) flux (32.7% and 50.5%, respectively). Under these conditions, no net change in PK flux was observed. When hepatocytes were preincubated with lactate and/or sulfonylurea addition for 30 min prior to radiolabeling with NaH14CO3, the metabolic state of the cells changed markedly. Glyburide produced a 34.6% decrease in glucose formation and a 31.3% decrease in PCOX flux, but no change in PK flux. In contrast, tolbutamide decreased glucose formation by 12.5% and increased PK flux by 53.2%, but no change in PCOX flux was observed. Such an increase in PK flux may be linked to tolbutamide-mediated increases in fructose-1,6-bisphosphate (F16P) via fructose-2,6-bisphosphate (F26P). These findings demonstrate that tolbutamide and glyburide decrease hepatic glucose production through various alterations in carbohydrate metabolism, depending upon the metabolic state of the cell. In addition, F26P may play a larger role in the hypoglycemic mechanism of action of tolbutamide than glyburide, since pyruvate carboxylase accounted for most of the decrease in glucose formation observed with glyburide and because preincubation with tolbutamide resulted in an activation of PK.

Animals↗