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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↗
PubMed1988

A system approach to pharmacodynamics. II: Glyburide pharmacodynamics and estimation of optimal drug delivery.

A system approach to the analysis of pharmacodynamic systems is applied to the relationship between the glyburide serum concentration (Cd) and a resulting pharmacologic effect response, that is, the C-peptide serum concentration (Cc) in patients with non-insulin dependent diabetes mellitus (NIDDM). Glyburide, glucose, and C-peptide serum concentrations were measured in eight patients with NIDDM following each of five treatments: Treatment A: one glyburide 5-mg tablet (formulation 1); Treatment B: one glyburide 5-mg tablet (formulation 2); Treatment C: glyburide solution as an intragastric infusion (4.67 mg over 12 h); Treatment D: glyburide solution as an intragastric infusion (9.33 mg over 12 h); and Treatment E: no glyburide. The overall relationship between the C-peptide (Cc), glyburide (Cd), and glucose (Cg) serum concentrations is successfully described by operator equations of the form, Cc(t) = t-infinity psi p(t-u)phi t(Cd(u), Cg(u)) du or Cc(t) = t-infinity psi p(t-u)phi t(Cd(u), Cg(u),u) du. The forms of the individual functions are selected empirically based on the results of the present study and those of previous investigations, and are estimated by conventional curve-fitting procedures. The resulting operator equations are used to describe glyburide pharmacodynamics in NIDDM patients and to estimate the optimal glyburide systemic concentration and delivery rate profiles for such patients based on pharmacodynamic response.

Blood Glucose↗
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↗
PubMedDate not supplied

Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment.

Fourteen non-insulin-dependent diabetic (NIDDM) patients continued their previous medication (7 on glyburide, 7 on glipizide) for 6 mo, after which they switched to the alternate treatment for another 6 mo. The treatment periods were followed by 1 mo of placebo. The sulfonylurea dose was increased to achieve fasting plasma glucose levels less than 9 mM or to a total maximum daily dose of 25 mg. The mean final doses of glyburide (14.7 +/- 2.4 mg/day) and glipizide (15.2 +/- 2.2 mg/day) were similar. Postprandial (postdose) glipizide levels were higher than those of glyburide, whereas fasting (predose) glyburide concentrations were higher than those of glipizide. Both treatments improved glucose control by 25% compared with placebo. Glipizide therapy evoked higher postprandial insulin concentrations than did glyburide, whereas basal insulin concentrations were higher during glyburide. Insulin sensitivity, assessed by an insulin tolerance test, was more improved with glyburide than with glipizide. In conclusion, overall glucose control is similarly improved by glyburide and glipizide. However, glipizide amplifies the plasma insulin response to meals more than glyburide, whereas glyburide enhances basal insulin secretion more than glipizide. Both pharmacokinetic and pharmacodynamic factors may contribute to these differences.

Blood Glucose↗
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↗
PubMed1989

Glyburide enhances the responsiveness of the beta-cell to glucose but does not correct the abnormal patterns of insulin secretion in noninsulin-dependent diabetes mellitus.

Eleven patients with noninsulin-dependent diabetes mellitus were studied before and after 6-10 weeks of glyburide therapy. Patients were studied during a 24-h period on a mixed diet comprising 30 Cal/kg divided into three meals. The following day a hyperglycemic clamp study was performed, with glucose levels clamped at 300 mg/dL (16.7 mmol/L) for a 3-h period. Insulin secretion rates were calculated by deconvolution of peripheral C-peptide concentrations using individual C-peptide clearance kinetics derived after bolus injection of biosynthetic human C-peptide. After 6-10 weeks on glyburide, the identical studies were repeated. In response to glyburide, the fasting plasma glucose level decreased from 12.3 +/- 1.2 to 6.8 +/- 0.9 mmol/L. Although the mean glucose over the 24 h of the meal study decreased from 12.7 +/- 1.4 to 10.8 +/- 1.2 mmol/L, postprandial hyperglycemia persisted on therapy, and after breakfast, glucose levels exceeded 10 mmol/L and did not return to fasting levels for the remainder of the day. Fasting serum insulin, plasma C-peptide, and the insulin secretion rate were not different before (152 +/- 48 pmol/L, 0.82 +/- 0.16 pmol/mL, and 196 +/- 34 pmol/min, respectively) and after (186 +/- 28 pmol/L, 0.91 +/- 0.11 pmol/mL, and 216 +/- 23 pmol/min, respectively) glyburide treatment despite lowering of the glucose level. However, average insulin and C-peptide concentrations over the 24-h period increased from 366 +/- 97 pmol/L and 1.35 +/- 0.19 pmol/mL to 434 +/- 76 pmol/L and 1.65 +/- 0.15 pmol/mL, respectively. The total amount of insulin secreted over the 24-h period rose from 447 +/- 58 nmol before therapy to 561 +/- 55 nmol while receiving glyburide. Insulin secretion was demonstrated to be pulsatile in all subjects, with periodicity ranging from 2-2.5 h. The number of insulin secretory pulses was not altered by glyburide, whereas pulse amplitude was enhanced after lunch and dinner, suggesting that the increased insulin secretion is characterized by increased amplitude of the individual pulses. In response to a hyperglycemic clamp at 300 mg/dL (16.7 mmol/L), insulin secretion rose more than 2-fold, from 47 +/- 9 nmol over the 3-h period before treatment to 103 +/- 21 nmol after glyburide therapy. We conclude that the predominant mechanism of action of glyburide in patients receiving therapy for 6-10 weeks is to increase the responsiveness of the beta-cell to glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1987

Glyburide sensitizes perfused rat liver to insulin-induced suppression of glucose output.

Glyburide, a second-generation sulfonylurea, is used in the treatment of NIDDM because of its hypoglycemic action. However, the site and mechanism of action of this sulfonylurea remain unclear. We examined the ability of glyburide to enhance insulin's inhibitory effect on glucagon-stimulated hepatic glucose production. The livers of fed male rats were perfused with a Krebs-Henseleit buffer containing washed human red blood cells. After a 60-min control period during which the liver was exposed to both insulin and glucagon (10 microU/ml and 11 pg/ml, respectively), the glucagon concentration was increased to 88 pg/ml in the presence of 0, 10, 40, and 240 microU/ml of insulin. Hepatic glucose output and phosphorylase a activity were monitored during the control and elevated-glucagon periods. The glyburide-infused group received glyburide (1.6 microgram/ml) during both the control and elevated-glucagon periods. As expected, high levels of insulin suppressed glucagon-stimulated glucose production and phosphorylase activation. Insulin at a concentration of 10 microU/ml was unable to suppress glucagon's stimulation of glucose production or its activation of phosphorylase. However, in the presence of glyburide it was able to decrease stimulated hepatic glucose production and phosphorylase activation by 40 and 50% respectively. In the absence of insulin, glyburide was unable to suppress glucagon's glycogenolytic action, suggesting that the drug potentiates insulin's action on the liver rather than exerting an inhibitory effect directly. Insulin at a concentration of 240 microU/ml completely suppressed glucagon action, and glyburide had no additional effect. Therefore, glyburide is able to enhance the sensitivity of the perfused rat liver to insulin without altering maximal insulin responsiveness.

Animals↗
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↗
PubMedDate not supplied

Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects.

Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.

Animals↗
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↗
PubMed1988

Glyburide increases cytosolic-free calcium concentrations in normal rat pancreatic islet cells.

We have attempted to delineate the effect of glyburide on the regulation of cytosolic-free calcium concentrations, [Ca2+]i, in normal rat pancreatic islet cells. In the presence of extracellular calcium (1 mmol/L), glyburide increased [Ca2+]i from 70 nmol/L to 260 nmol/L in a dose-dependent manner. The maximal effect was seen at a concentration of 2 mumol/L with half-maximal stimulation observed at .25 mumol/L. The effect of glyburide (.25 mumol/L) was inhibited 90% by the calcium channel blocker, verapamil (30 mumol/L). At a maximally effective concentration of glyburide (2 mumol/L), the inhibitory effect of verapamil was only 17%. In the absence of extracellular calcium, glyburide increased [Ca2+]i from 55 nmol/L to 107 nmol/L, indicating its ability to mobilize intracellular calcium stores. These results correlated well with the ability of glyburide (2 mumol/L) to stimulate insulin secretion both in the presence (from 38 +/- 5 mumol/L/10 islets to 131 +/- 28 microU/10 islets) and in the absence (from 49 +/- 4 microU/10 islets to 93 +/- 7 microU/10 islets) of extracellular Ca2+. The present observations suggest that glyburide promotes calcium influx via voltage-dependent calcium channels and may mobilize intracellular calcium stores.

Animals↗