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At least 19 recordsLinked to original sources

PubMed1999

A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients.

In the present study we assessed and compared the effectiveness and safety of preconstituted, fixed, combinations of low-dose glyburide plus metformin with higher-dose glyburide monotherapy in patients with type 2 diabetes. This randomized, double-blind, cross-over study comprised 40 patients. After a 30-day run-in period of dietary treatment, patients received combined glyburide (5, 7.5 or 10 mg/day) and metformin (800, 1,200 or 1,600 mg/day) as preconstitued, fixed combinations, or glyburide alone (5, 10 or 15 mg/day). The dose was increased stepwise so as to have 1 (T1), 2 (T2) and 3 (T3) months of treatment for any given regimen (6 months in total). After 2 weeks of washout (T4), the groups were then crossed over (T5, T6, T7 periods). Body weight, fasting plasma glucose, HbA(1c), blood lactate, total cholesterol and HDL-cholesterol, and triglycerides were measured at the beginning and end of T1 and T5, and end of T2, T3, T6 and T7; postprandial plasma glucose, fasting and postprandial plasma insulin and C-peptide were evaluated at the beginning of T1 and T5, and end of T3 and T7. At these latter time points additional assessments included routine clinical chemistry measurements, ECG, and ophthalmoscopic examination. Statistical analysis was performed by the paired Student's t-test and analysis of variance for cross-over studies. Thirty-three patients completed the study. Fasting plasma glucose, postprandial plasma glucose and HbA(1c) levels improved significantly during combined treatment with glyburide at lower doses plus metformin. This effect was achieved without any major change of insulin and C-peptide concentrations. Circulating lactate concentrations increased during the regimen including metformin, but they remained well within the reference values for normal subjects. Plasma total cholesterol and triglycerides levels remained substantielly unchanged throughout the study, whereas HDL-cholesterol concentrations increased slightly, but significantly, with glyburide plus metformin therapy. Routine clinical chemistry measurements, ECG and ophthalmoscopic examinations did not change during the study. These results demonstrate that improved metabolic control can be achieved with preconstituted, fixed combinations of low-dose glyburide plus metformin in patients with type 2 diabetes, compared to higher doses of the sulphonylurea alone.

Blood Glucose↗

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↗

PubMedDate not supplied

[A comparative study of insulin and glyburide versus glyburide or insulin in the chronic control of patients with type-2 diabetes].

In order to know the usefulness of a combined treatment with gliburide and NPH insulin 25 patients with well controlled type II diabetes mellitus were studied. The patients were randomly divided in to three groups: Group I just received gliburide, Group II only insulin and Group III gliburide and insulin. Glucose in fast, glycosylated haemoglobin and C peptide levels were determined over five months. For the statistical data processing variance analysis was performed. The initial and final glucose determinations were: Group I, 169.3 mg% and 139.0 mg% respectively (p > 0.05); Group II, 202.1 mg% and 177 mg% (p > 0.05); Group III, 157.8 mg% and 158.8 mg% (p > 0.1) for the glycosylated haemoglobin the determinations were: Group I, 7.2% and 5.1% (p > 0.05); Group II, 6.2% and 5.1% (p > 0.05) and Group III, 5.7% and 4.7% (p > 0.05). For the C peptide were 2.5 and 4.5 for Group I (p > 0.05), 2 and 4.1 for Group II (p > 0.05) and 3.2 and 5.3 for Group III (p > 0.05) with no significant statistical differences. It is concluded that the combined treatment showed to be effective, but not superior, in order to control diabetic patients and it can be a useful therapeutic alternative in well selected patients.

Adult↗

PubMed2005

Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome.

OBJECTIVE: We sought to investigate the association between glyburide dose, degree of severity in gestational diabetes mellitus (GDM), level of glycemic control, and pregnancy outcome in insulin- and glyburide-treated patients. STUDY DESIGN: In a secondary analysis of our previous randomized study, 404 women were analyzed. The association among glyburide dose, severity of GDM, and selected maternal and neonatal factors was evaluated. Severity levels of GDM were stratified by fasting plasma glucose (FPG) from the oral glucose tolerance test (OGTT). Infants with birth weight at or above the 90th percentile were considered large-for-gestational age (LGA). Macrosomia was defined as birth weight > or =4000 g. Well-controlled was defined as mean blood glucose < or =95 mg/dL. The association between glyburide- and insulin-treated patients by severity of GDM and neonatal outcome was evaluated. RESULTS: The dose received for the glyburide-treated patients was 2.5 mg-32%; 5 mg-23%; 10 mg-17%; 15 mg-8%; and 20 mg-20%. Patients were grouped into low (< or =10 mg) and high (>10 mg) daily dose of glyburide. A comparison between severity of the disease (fasting plasma glucose categories) and highest dose of glyburide revealed a significant difference between the low-95 FPG and the other severity categories (P = .02). Of patients in the well-controlled glycemic group, only 6% required the high dose of glyburide (>10 mg). In patients with poor glycemic control (mean blood glucose >95 mg/dL), 38% received the high dose of glyburide (P = .0001). Comparison between the high glyburide (>10 mg) and the low glyburide dosages (< or =10 mg) revealed that the rate of macrosomia was 16% vs 5% and LGA 22% vs 8%, (P = .01), respectively. No significant difference was found in composite outcome, metabolic complications, and Ponderal Index between the 2 dose groups. Stratification by disease severity revealed a significantly lower rate of LGA for both the glyburide- and insulin-treated subjects. No significant difference was found between metabolic, respiratory, and neonatal intensive care unit (NICU) for patients within each fasting plasma glucose severity category. CONCLUSION: Glyburide and insulin are equally efficient for treatment of GDM in all levels of disease severity. Achieving the established level of glycemic control, not the mode of pharmacologic therapy, is the key to improving the outcome in GDM.

Administration, Oral↗

PubMed1996

Effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy subjects.

OBJECTIVE: To determine the effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers. DESIGN: Single-center, randomized, two-way, crossover design following an initial baseline evaluation phase. SETTING: Outpatient, university-based ambulatory care facility. PATIENTS: Sixteen healthy nonsmoking men aged 20-34 years. INTERVENTION: Three phases consisting of six treatments. Phase 1 began with treatment A, a baseline oral glucose tolerance test (GTT), followed by treatment B, glyburide 5 mg plus a GTT. The other two phases were administered in a crossover design. Phase 2 consisted of the administration of aspirin 975 mg qid for 4 days. On day 3 a GTT was administered (treatment C) and on day 4 glyburide 5 mg plus a GTT was administered (treatment E). Phase 3 consisted of the administration of ibuprofen 600 mg qid for 4 days with a GTT on day 3 (treatment D) and glyburide 5 mg plus a GTT on day 4 (treatment F). MAIN OUTCOME MEASURES: Serum glyburide concentrations after each treatment, as well as glucose and insulin, ibuprofen, and salicylate serum concentrations and glyburide free fractions. RESULTS: Aspirin administration resulted in an 85% increase in mean total glyburide oral clearance and a 29% increase in glyburide free fraction. Ibuprofen administration resulted in a slight increase in mean glyburide free fraction, but no significant changes in glyburide pharmacokinetic parameters were observed. Insulin concentrations were increased during the glyburide plus aspirin treatment. Conflicting results were observed in the glucose parameters. CONCLUSIONS: The potential for this glyburide-aspirin interaction resulting in a transient hypoglycemia should be considered in diabetic patients receiving glyburide therapy.

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↗

PubMedDate not supplied

Vascular pharmacology of ATP-sensitive K+ channels: interactions between glyburide and K+ channel openers.

This study in isolated rabbit superior artery (RMA) investigated the interactions between glyburide, a known blocker of vascular ATP-sensitive K+ channels (KATP), and several chemically diverse potassium channel openers (PCOs): minoxidil sulfate (MNXS; 5 microM), pinacidil (1 microM), cromakalim (0.5 microM) and RP-49356 (1 microM; a PCO from Rhône Poulenc). Relaxation time courses for these PCOs were obtained in norepinephrine (NE; 5 microM)-precontracted RMA, and the concentrations of PCOs found to be equipotent to each other in terms of the degree of maximum relaxation (about 80%) and the time course of relaxation (within 15 min) were chosen for further study. This was taken as a functional indicator of a similar degree as well as similar kinetics of K+ channel opening by these PCOs. Pretreatment with glyburide (10-500 nM) produced a dose-dependent inhibition of the PCO relaxation time course. The glyburide IC50s against pinacidil, MNXS and RP-49356 were statistically similar and ranged from 72-79 nM. The glyburide IC50 against cromakalim was a modest 2-fold higher, at 148 nM. In contrast, pretreatment with charybdotoxin (200 nM) produced no significant inhibition of the maximum relaxation produced by these PCOs. Furthermore, glipizide, a sulfonylurea that is 10- to 25-fold less potent than glyburide for insulin secretion, was found to be 20- to 30-fold less potent than glyburide as a vascular KATP antagonist. These data suggest a mechanistic model in which these structurally diverse PCOs share a common critical step in the sequence of events leading to the KATP opening, and that glyburide interferes with this common critical step to produce a similar type of blockade against all four PCOs. Interaction studies with glyburide and pinacidil demonstrated 15 min to be the optimal pretreatment time for glyburide to produce maximal inhibition. Glyburide also reversed existing pinacidil relaxation regardless of the degree of pre-existing relaxation. These data suggest that glyburide is able to produce its blockade regardless of the state of K+ channel activation. Studies on the effect of pH (6.4 vs. 7.3) showed that at acidic pH, pinacidil became less effective and the effectiveness of glyburide was significantly enhanced, whereas the actions of D600 remained unchanged. These data suggest the effects of both openers and blockers of the KATP are strongly pH dependent.

Animals↗

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↗

PubMed2006

Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety.

OBJECTIVE: Gestational diabetes affects up to 5% of women. Oral hypoglycemics have been avoided because of the assumption that their placental transfer may cause fetal-neonatal hypoglycemia. A recent randomized trial could not show measurable glyburide levels in umbilical blood despite maternal treatment with regular doses of glyburide. The mechanism underlying this phenomenon is not known. The objective of our study was to document, using a human placenta perfusion model, whether glyburide is actively effluxed from the fetal to the maternal circulation. STUDY DESIGN: In vitro perfusion studies of human cotyledon were performed to quantify placental transfer of glyburide. Using close circle experiments and introducing glyburide to both maternal and fetal circulations at 200 ng/mL, we looked for evidence of transport against concentration gradient from the fetus to the mother. In parallel experiments, the P-glycoprotein inhibitor verapamil was used in an attempt to inhibit transplacental glyburide movement. RESULTS: There was highly significant transfer of glyburide against concentration gradient from the fetal to the maternal circulation. Fetal-to-maternal concentration ratio was 0.92 +/- 0.23 at the start of the experimental period and 0.31 +/- 0.47 3 hours later (P = .01) (n = 5). Verapamil did not modify glyburide transport. CONCLUSION: This is the first direct evidence of active glyburide transport from the fetus to the mother and, in general, of any medicinal drug used during pregnancy. These experiments suggest that glyburide is actively efflux by a transporter other than P-glycoprotein. Alternatively, it is possible that a minority of glyburide is carried by P-glycoprotein, but most of the fetal load is pumped to the mother by a yet-unidentified placental transport system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons.

Glyburide (glibenclamide) is a second-generation sulfonylurea used for treatment of type-2 and gestational diabetes mellitus. To date, two glyburide metabolites have been identified in maternal urine: namely, 4-trans-hydroxycyclohexyl glyburide and 3-cis-hydroxycyclohexyl glyburide. The use of glyburide to treat gestational diabetes prompted us to investigate its metabolism by the placenta. The metabolism of glyburide by microsomal preparations from human and baboon placenta was compared with metabolism by their livers. The metabolites formed by the microsomes of the four tissues were identified by high-performance liquid chromatography-mass spectrometry using retention times, ion current (extracted at m/z 510), and selected-ion monitoring. The data obtained revealed the formation of six distinct hydroxylated derivatives of glyburide by each of the four microsomal preparations. However, the amounts of the six metabolites formed by the placentas were a fraction of that formed by the livers. Moreover, the relative quantities of each metabolite formed differed between species as well as between the two tissues. Also, the structure of the unidentified metabolites was determined by comparison with synthesized standards. These metabolites were identified as the 4-cis-hydroxycyclohexyl glyburide, 3-trans-hydroxycyclohexyl glyburide, and 2-trans-hydroxycyclohexyl glyburide. Therefore, one glyburide metabolite remains to be identified, but the data we obtained allowed us to suggest its structure.

Adult↗

PubMed2002

Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers.

BACKGROUND: Glyburide (INN, glibenclamide) is a second-generation sulfonylurea antidiabetic agent with high potency. We hypothesized that glyburide may be a substrate of cytochrome P450 2C9 (CYP2C9), an enzyme that has two low-activity amino acid variants-Arg144Cys (CYP2C9*2) and Ile359Leu (CYP2C9*3). We explored the impact of these polymorphisms on glyburide pharmacokinetics and the effects on insulin and glucose concentrations. METHODS: Twenty-one healthy volunteers who represented all possible combinations of the two variant alleles were studied (genotypes CYP2C9*1/*1, *1/*2, *2/*2, *1/*3, *2/*3, and *3/*3 ). They received a single oral dose of 3.5 mg glyburide followed by 75 g glucose at 1, 4.5, and 8 hours after administration of glyburide. Glyburide was quantified in plasma by reversed-phase HPLC. Venous blood concentrations of glyburide, insulin, and glucose were analyzed with a population pharmacokinetic-pharmacodynamic model by use of NONMEM statistical software. RESULTS: Pharmacokinetics of glyburide depended significantly on CYP2C9 genotypes. In homozygous carriers of the genotype *3/*3, total oral clearance was less than half of that of the wild-type genotype *1/*1 (P <.001). Correspondingly, insulin secretion measured within 12 hours after glyburide ingestion was higher in carriers of the genotype *3/*3 compared with the other genotypes (P =.028), whereas the differences in glucose concentrations were not significant. CONCLUSIONS: Carriers of the CYP2C9 variant *3 had decreased oral clearances of glyburide. This confirms that glyburide is metabolized by CYP2C9. Corresponding differences in insulin plasma levels indicated that dose adjustment based on CYP2C9 genotype may improve antidiabetic treatment.

Adult↗

PubMed2004

Use of glyburide for the treatment of gestational diabetes: the San Antonio experience.

OBJECTIVES: Equivalent efficacy of glyburide and insulin for treatment of gestational diabetes (GDM) was demonstrated in a recent randomized trial. We describe our experience with glyburide in practice, and suggest factors that predict failure of glyburide treatment. METHODS: Women with GDM treated with glyburide were studied. They were divided into two groups: those who achieved adequate glycemic control with glyburide, and those who did not. The groups were compared in terms of baseline characteristics, including diabetes risk factors and glucose testing values. Receiver operating characteristics (ROC) curves were generated to identify thresholds for fasting plasma glucose and body mass index (BMI) that would predict glyburide failure. RESULTS: Seventy-five women were analyzed: 63 (84%) were successfully treated with glyburide, and 12 (16%) were not. Baseline characteristics were similar between the groups, except that failures had higher 3-h glucose tolerance test (GTT) values at all time points. ROC curves for fasting plasma glucose, pre-pregnancy BMI and BMI at diagnosis revealed no cut-off points for predicting failure of glyburide therapy. However, when fasting plasma glucose value on the GTT was > or = 110 mg/dl, 24% of women failed to respond to glyburide, compared to 12% at < 110 mg/dl (p = 0.15). CONCLUSIONS: In treatment of GDM, glyburide is successful in achieving good glycemic control in most women. Women with high fasting plasma glucose levels, however, may not respond adequately to glyburide therapy.

Adult↗

PubMedDate not supplied

Improvements in glycemic control in type 2 diabetes patients switched from sulfonylurea coadministered with metformin to glyburide-metformin tablets.

OBJECTIVE: To evaluate the change in hemoglobin A1C (A1C) in patients with type 2 diabetes switched from coadministration of a sulfonylurea (SU), glyburide or glipizide, and metformin (SU+Met) to a single glyburide-metformin tablet. METHODS: A retrospective cohort study design of patients with type 2 diabetes treated at 3 Veterans Affairs Medical Centers and 1 Department of Defense Medical Center was utilized. One hundred percent of patients receiving glyburide-metformin tablets were screened for inclusion. Patients with at least 6 months of prior SU+Met combination therapy and a baseline A1C measured within 35 days prior to or 3 days after switch to glyburide-metformin tablets were included. At least one documented follow-up A1C at >or=90 days after the switch to glyburide-metformin was required for inclusion. Glycemic control, complications, lipid parameters, concomitant medications, and weight were analyzed prior to and following the switch to glyburide-metformin. RESULTS: Seventy-two patient records were included after the disqualification criteria excluded 488 prospective patients. The mean age of the 72 patients was 62 years; average body mass index was 32.9 kg/m2, average baseline A1C was 8.3%, and the average time since diagnosis was 7.6 years. The mean reduction in A1C was 0.6% (P=0.002) at a mean follow-up of 196 days after the switch to glyburide-metformin tablets. Improvement in glycemic control was predominantly seen in patients with a baseline A1C >or=8% in whom a 1.3% mean reduction in A1C (P=0.0002) was achieved despite a lower mean final dose of glyburide. CONCLUSION: The results of this study suggest that in type 2 diabetic patients with an A1C >or=8%, switching from coadministration of a sulfonylurea plus metformin to combination glyburide-metformin tablets may provide an improvement in glycemic control in the range of a 1.2 to 1.4 absolute percentage point decrease in A1C. A randomized, prospective trial comparing these 2 methods of treatment is needed, however, to determine the precise effect provided by the unique formulation of glyburide in the glyburide-metformin tablet.

Administration, Oral↗

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↗

PubMed2005

Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization.

OBJECTIVE: This study was undertaken to compare the use of glyburide with insulin for the treatment of gestational diabetes mellitus (GDM) unresponsive to diet therapy. STUDY DESIGN: A retrospective study was performed among women with singleton pregnancies who had GDM diagnosed, with fasting plasma glucose 140 mg/dL or less on glucose tolerance testing, between 12 and 34 weeks who failed diet therapy from 1999 to 2002. We identified 584 women and compared those treated with insulin between 1999 and 2000 with women treated with glyburide between 2001 and 2002. Maternal and neonatal outcomes and complications were assessed. Statistical methods included univariate analyses and multivariable logistic regression. RESULTS: In 1999 through 2000, 268 women had GDM diagnosed and were treated with insulin; in 2001 through 2002, 316 women had GDM diagnosed of which 236 (75%) received glyburide. The 2 groups were similar with regard to age, nulliparity, and historical GDM risk factors; however, women in the insulin group had a higher mean body mass index (31.9 vs 30.6 kg/m 2 , P=.04), a greater proportion identified themselves as white (43%, 28%, P<.001) and fewer as Asian (24%, 37%, P=.001), and they had a significantly higher mean fasting on glucose tolerance test (105.4 vs 102.4 mg/dL , P=.005) compared with the glyburide group. There were no significant differences in birth weight (3599+/-650 g vs 3661+/-629 g, P=.3), macrosomia (24%, 25%, P=.7), or cesarean delivery (35%, 39 %, P=.4). Women in the glyburide group had a higher incidence of preeclampsia (12%, 6%, P=.02), and neonates in the glyburide group were more likely to receive phototherapy (9%, 5%, P<.05), and less likely to be admitted to the neonatal intensive care unit (NICU) (15%, 24%, P=.008) though they had a longer NICU length of stay (4.3+/-9.6 vs 8.0+/-10.1, P=.002). Posttreatment glycemic control data were available for 122 women treated with insulin and 137 women treated with glyburide. More women in the glyburide group achieved mean fasting and postprandial goals (86%, 63%, P<.001). These findings remained significant in logistic regression analysis. CONCLUSION: In a large managed care organization, glyburide was at least as effective as insulin in achieving glycemic control and similar birth weights in women with GDM who failed diet therapy. The increased risk of preeclampsia and phototherapy in the glyburide group warrant further study.

Adult↗

PubMed1997

Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels.

INTRODUCTION: Adenosine triphosphate (ATP)-sensitive potassium (K+) channels are modulated by drugs, so that they are opened by vasodilators such as minoxidil but are closed by hypoglycemic agents such as glyburide (glibenclamide). Animal studies and in vitro evidence suggests that the coadministration of drugs with opposing effects on K+ channels attenuates their pharmacodynamic effects. METHODS: To investigate whether this important pharmacodynamic interaction occurs in humans, we administered 5 mg minoxidil, 2.5 mg glyburide or both in a double-blind fashion to nine healthy subjects. Glucose and insulin responses during an intravenous glucose tolerance test (0.3 gm/kg) were measured and blood pressure was recorded for 8 hours. In an additional four subjects the effect of 5 mg glyburide on the hypotensive effect of 5 mg minoxidil was examined. RESULTS: None of the parameters of glucose metabolism differed significantly when subjects received glyburide alone, minoxidil alone, or glyburide with minoxidil. Minoxidil or minoxidil in combination with 2.5 mg glyburide resulted in a similar significant decrease in blood pressure compared with the response to glyburide alone. The hypotensive effect of minoxidil was smaller in the four subjects who received the higher dose of glyburide, but significant hypoglycemia (blood glucose concentration < 60 mg/dl) occurred in three of the four subjects. CONCLUSION: We conclude that, in healthy volunteers, the coadministration of 2.5 mg glyburide and 5 mg minoxidil does not result in attenuation of the blood pressure-lowering effect of minoxidil. The smaller hypotensive response in four subjects who received 5 mg glyburide and 5 mg minoxidil suggests the possibility of a dose-related drug interaction. Studies with strict clamping of blood glucose concentrations will be required to address this possibility.

Adult↗

PubMed2003

Greater reductions in A1C in type 2 diabetic patients new to therapy with glyburide/metformin tablets as compared to glyburide co-administered with metformin.

BACKGROUND: A cohort of patients with type 2 diabetes, prescribed glyburide/metformin tablets, experienced significantly greater improvements in glycaemic control compared to patients receiving glyburide co-administered with metformin. AIM: To compare the change in A1C for type 2 diabetic patients new to combination therapy with fixed-dose glyburide/metformin tablets vs. glyburide co-administered with metformin in a usual-care setting. METHODS: This retrospective cohort study analysed medication usage via an administrative pharmacy claims database and the patients' corresponding laboratory results. Patients were new to antidiabetic combination therapy with glyburide/metformin tablets or glyburide co-administered with metformin between August 2000 and July 2001 and had A1C measurements at baseline and within 76-194 days of initiating combination therapy. The change from baseline in A1C was analysed using statistical regression to adjust for significant covariates (baseline A1C and dosage). Adherence with therapy was also compared. RESULTS: The cohort consisted of 950 patients who received glyburide/metformin tablets and 471 taking glyburide co-administered with metformin. Glyburide/metformin patients were younger (mean age = 56 vs. 60 years, p < 0.0001) and received lower doses of each drug than patients taking glyburide co-administered with metformin (glyburide mean final dose = 6 vs. 10 mg/day, p < 0.0001; metformin = 893 vs. 1297 mg/day, p < 0.0001). The mean decrease from baseline A1C, adjusted for baseline A1C and dosage, of 2.02% for glyburide/metformin tablets was significantly (p < 0.0001) greater than the decrease of 1.49% for glyburide co-administered with metformin. Glyburide/metformin patients with baseline A1C >/= 8 experienced a significantly (p < 0.0001) greater decrease in A1C of 2.93% compared to 1.92% for glyburide co-administered with metformin. For patients with baseline A1C < 8%, the difference between the A1C responses remained significant, even though the reductions in A1C were smaller for both glyburide/metformin tablets and glyburide co-administered with metformin (0.54% and 0.23%, p = 0.0017). Patients were more adherent with glyburide/metformin tablets (84% vs. 76%, p < 0.0001), though regression analysis indicated that adherence was not a significant predictor of change in A1C. CONCLUSIONS: The lower medication doses delivered by glyburide/metformin tablets provided a significantly greater reduction in A1C than did glyburide co-administered with metformin in patients with type 2 diabetes, especially when baseline A1C >/= 8%.

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