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At least 19 recordsLinked to original sources
PubMed1994

Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM.

OBJECTIVE: To compare the efficacy and safety of controlled-release glipizide (glipizide-GITS [gastrointestinal therapeutic system]) and immediate-release glipizide in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation. Plasma glucose, serum insulin, C-peptide, and plasma glipizide levels were measured at fasting and post-Sustacal challenge at the end of 1 and 8 weeks of each treatment phase. HbA1c was measured at the end of weeks 7 and 8 of each treatment phase. RESULTS: Both formulations of glipizide yielded similar mean HbA1c values. However, mean fasting plasma glucose (FPG) levels were significantly lower with glipizide-GITS treatment than with immediate-release glipizide at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fasting insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate-release glipizide. Glucose responses to Sustacal were similar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-GITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stable by the end of week 1, and the concentrations increased proportionately with dose. Once-daily Glipizide-GITS provided effective mean glipizide concentrations (> 50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated. CONCLUSIONS: Glipizide-GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial plasma glucose levels equally; however, glipizide-GITS exerted its control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C-peptide levels. This suggests that glipizide-GITS improves insulin sensitivity.

Administration, Oral↗
PubMed2002

Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediate-release glipizide in patients with type II diabetes mellitus.

This study was designed to compare the pharmacokinetic and short-term pharmacodynamic profile of extended-release glipizide GITS (Glucotrol XL) given in a dosage of 20 mg once daily with that of immediate-release glipizide (Glucotrol) 10mg twice daily in patients with type II diabetes mellitus. In an open-label, randomized, two-way crossover study, each glipizide formulation was administered for 5 days. Serial blood samples were drawn at baseline and on the 5th day of each treatment phase for measurement of glipizide, glucose, insulin, and C-peptide concentrations. At steady state, the mean Cmax after immediate-release glipizide was significantly greater than after glipizide GITS, and the tmax was considerably shorter. Although the mean Cmin with glipizide GITS was about 80% higher than with immediate-release glipizide, the mean AUC0-24 was significantly lower. Despite the lower plasma concentrations with glipizide GITS in this short-term study, the two formulations had similar effects on serum concentrations of glucose, insulin, and C-peptide. The absence of a pronounced peak plasma concentration with the GITS formulation might confer advantages in terms of maintaining clinical effectiveness and reducing the potential to cause adverse effects.

Adult↗
PubMed1997

Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group.

OBJECTIVE: To investigate the efficacy, safety, and dose-response characteristics of an extended-release preparation of glipizide using the gastrointestinal therapeutic system (GITS) on plasma glucose, glycosylated hemoglobin (HbA1c), and insulin secretion to a liquid-mixed meal in NIDDM patients. RESEARCH DESIGN AND METHODS: Two prospective, randomized, double-blind, placebo-controlled, multicenter clinical trials were performed in 22 sites and 347 patients with NIDDM (aged 59 +/- 0.6 years; BMI, 29 +/- 0.3 kg/m2; known diabetes duration, 8 +/- 0.4 years) were studied. Each clinical trial had a duration of 16 weeks with a 1-week washout, 3-week single-blind placebo phase, 4-week titration to a fixed dose, and 8-week maintenance phase at the assigned dose. In the first trial, once-daily doses of 5, 20, 40, or 60 mg glipizide GITS were compared with placebo in 143 patients. In the second trial, doses of 5, 10, 15, or 20 mg of glipizide GITS were compared with placebo in 204 patients. HbA1c, fasting plasma glucose (FPG), insulin, C-peptide, and glipizide levels were determined at regular intervals throughout the study. Postprandial plasma glucose (PPG), insulin, and C-peptide also were determined at 1 and 2 h after a mixed meal (Sustacal). RESULTS: All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82%). Pharmacodynamic analysis indicated a significant relationship between plasma glipizide concentration and reduction in FPG and HbA1c over a dose range of 5-60 mg, with maximal efficacy achieved at a dose of 20 mg for FPG and at 5 mg for HbA1c. PPG levels were significantly lower, and both postprandial insulin and C-peptide levels significantly higher in patients treated with glipizide GITS compared with placebo. The percent reduction in FPG was comparable across patients with diverse demographic and clinical characteristics, including those with entry FPG > or = 250 mg/dl, resulting in greater absolute decreases in FPG and HbA1c in patients with the most severe hyperglycemia. Despite the forced titration to a randomly assigned dose, only 11 patients in both studies discontinued therapy because of hypoglycemia. Glipizide GITS did not alter lipids levels or produce weight gain. CONCLUSIONS: The once-daily glipizide GITS 1) lowered HbA1c, FPG, and PPG over a dose range of 5-60 mg, 2) was maximally effective at 5 mg (using HbA1c) or 20 mg (using FPG) based on pharmacokinetic and pharmacodynamic relationships, 3) maintained its effectiveness in poorly controlled patients (those with entry FPG > or = 250 mg/dl), 4) was safe and well tolerated in a wide variety of patients with NIDDM, and 5) did not produce weight gain or adversely affect lipids.

Adult↗
PubMed1979

Plasma levels of glucose and lactate after intravenous glipizide administration in some insulin-dependent diabetics. Therapeutic effects of an associated glipizide-insulin treatment.

A study was carried out to evaluate the effectiveness of glipizide in insulin-dependent diabetic patients. An intravenous glipizide (2 mg) test was carried out in 7 patients before and after a period of associated insulin-glipizide treatment (mean daily dose of 80.7 i.v. lente insulin and 14.3 mg glipizide for 9.1 months) to assess the capacity of the sulphonylurea to reduce acutely the plasma glucose and lactate levels. Glipizide did not produce glucose variations in either test but did result in a significant decrease, in the first test only, in mean plasma baseline levels of lactate, which were higher than normal in these patients. There was no reduction in daily insulin requirements after the period of associated glipizide-insulin treatment. It is concluded that, in the dosage used, intravenous glipizide probably has no hypoglycaemic effects in insulin-dependent diabetics. Moreover, it did not prove useful in combination with insulin. However, the reduction in plasma lactate may be related to an acute enhancement of the exogenously administered insulin. This improvement in the insulin effect may be an acute one among the so called "extra-pancreatic" actions which have been demonstrated for glipizide and other sulphonylureas.

Adult↗
PubMed2000

Glipizide. A review of the pharmacoeconomic implications of the extended-release formulation in type 2 diabetes mellitus.

UNLABELLED: Glipizide is a second generation sulphonylurea agent that is available in a Gastrointestinal Therapeutic System (GITS) extended-release formulation. Glipizide GITS provides more stable plasma drug concentrations than the immediate-release formulation and the once-daily regimen may optimise patient compliance. In patients with type 2 diabetes mellitus, glipizide GITS is at least as effective as the immediate-release formulation of glipizide in providing glycaemic control, and may have a greater effect on fasting plasma glucose levels. Any therapeutic advantage over other antidiabetic agents remains to be established, but in a preliminary report (n = 40) glipizide GITS provided better glycaemic control and produced less fasting insulinaemia than glibenclamide (glyburide). The incidence of hypoglycaemic symptoms with glipizide GITS is low (< or = 3%). Quality of life was improved compared with baseline after 12 weeks' treatment with glipizide GITS 5 to 20 mg/day plus diet in a US double-blind, placebo-controlled trial in 569 patients with type 2 diabetes mellitus. Hyperglycaemic symptom-related distress decreased with glipizide GITS treatment, while hypoglycaemic symptom-related distress was not significantly increased compared with placebo plus diet. Quality of life during glipizide GITS treatment has not been compared with that during treatment with other antidiabetic agents. Monthly productivity losses related to absenteeism were $US91 (1995 values) per patient lower in the glipizide GITS group compared with the placebo group in the latter prospective study. Productivity parameters improved slightly or did not change significantly in the glipizide GITS group, but deteriorated in the placebo group. Differences in direct healthcare costs between groups were small and not comprehensively reported. Glipizide GITS was the least costly strategy for first-line therapy in a US cost-of-treatment model of the first 3 years after diagnosis of type 2 diabetes mellitus. The total per-patient cost was $US4867 with glipizide GITS, $US5196 with metformin and $US5249 with acarbose (1996/1997 values). Monthly drug acquisition costs were lower, and glycosylated haemoglobin levels and patient compliance were improved, after formulary conversion from the immediate-release to the GITS formulation of glipizide in a US single-hospital retrospective analysis. CONCLUSIONS: Glipizide GITS produced better cost outcomes than metformin and acarbose in a model of 3 years' treatment of type 2 diabetes mellitus. Glipizide GITS had pharmacoeconomic and quality of life advantages over diet alone in the short term, but more clinically relevant comparisons with other antidiabetic agents are needed. There are limitations to the present data, but the available pharmacoeconomic data have been favourable for glipizide GITS.

Delayed-Action Preparations↗
PubMedDate not supplied

Effects of glipizide GITS and glibenclamide on metabolic control, hepatic glucose production, and insulin secretion in patients with type 2 diabetes.

OBJECTIVE: Evaluation of effects of glipizide gastrointestinal therapeutic system (GITS) administered once daily (AM or PM) and glibenclamide on glycemic control, insulin secretory response, and hepatic glucose production (HGP) in patients with type 2 diabetes. METHODS: In a randomized, double-blind, and placebo-controlled study, subjects (HbA(1c) between 8.6 and 10.0%) received a titrated daily dose (5-20 mg) of either glipizide GITS AM (n = 11), glipizide GITS PM (n = 10), glibenclamide (n = 11), or placebo (n = 10) for eight weeks. Fasting and 24-h glucose and insulin, HGP, fructosamine, and HbA(1c) were measured at baseline and at study conclusion; glucose and insulin were also evaluated after Sustacal challenge. RESULTS: Fasting and 24-h glucose were significantly reduced by glipizide GITS AM (33%, p < 0.001; 39%, p < 0.0001), glipizide GITS PM (33%, p < 0.0001; 32%, p < 0.0001), and glibenclamide (37%, p < 0.05; 37%, p < 0.0001). Fasting insulin was not significantly increased by any treatment; 24-h insulin was not increased by glipizide GITS AM, but was elevated by glipizide GITS PM (39%, p < 0.05) and glibenclamide (23%, p < 0.05). Fructosamine and HbA(1c) were significantly reduced by glipizide GITS AM (28%, p < 0.001; 22%, p < 0.0001), glipizide GITS PM (25%, p < 0.005; 24%, p < 0.005), and glibenclamide (17%, p < 0.001; 14%, p < 0.05). Glipizide GITS AM and glibenclamide significantly reduced HGP by approximately 19% (p < 0.05) and 17% (p < 0.01) respectively. Glipizide GITS and glibenclamide significantly (p < 0.0001) decreased the glucose excursion after Sustacal challenge. The reductions in glucose excursions were accompanied by significant (p < 0.05) increases in the insulin response, suggesting an improvement in meal-related insulin secretion. CONCLUSIONS: Glipizide GITS and glibenclamide treatment are effective agents for improving fasting plasma glucose and HbA(1c). Each possessed a suppressive effect on basal HGP and improved postprandial glycemia, but only glipizide GITS AM was effective without causing a persistent elevation in insulin. This profile of glipizide GITS AM is therapeutically attractive, as it is consistent with the potential for a reduced risk of hypoglycemia.

Adult↗
PubMed1986

Effects of glipizide on various consecutive insulin secretory stimulations in patients with type 2 diabetes.

Immunoreactive insulin (IRI) and C-peptide secretory responses to consecutive stimulations with terbutaline, glucagon, glucose and a standard meal were investigated in fasted subjects with newly diagnosed, untreated Type 2 diabetes with and without concomitant administration of the sulphonylurea agent glipizide (5 mg). Basal concentrations of blood glucose were 8.7 +/- 0.8 mmol/l without glipizide, and 6.6 +/- 0.5 mmol/l with glipizide (p less than 0.01). This difference in prestimulation glucose levels persisted throughout the study. It was found that glipizide potentiated the IRI and C-peptide secretion in response to terbutaline (125 micrograms i.v.). The absolute IRI and C-peptide secretory responses to glucagon (250 micrograms i.v.) were of similar magnitudes with or without glipizide, despite the lower blood glucose concentrations after glipizide. Allowing for the lower blood glucose, IRI and C-peptide responses to glucagon were potentiated by glipizide. Glucose (6 g i.v.) exerted no IRI or C-peptide secretory effect in these patients either without or with glipizide. The changes in blood glucose concentration after injection of glucagon were not altered by glipizide. On the contrary, the terbutaline-induced increment in blood glucose concentration was inhibited by glipizide and the glucose elimination rate after glucose injection was slightly enhanced by glipizide; effects explained by the higher plasma insulin levels. After meal ingestion, the absolute IRI and C-peptide secretory responses were slightly enhanced by glipizide. Glipizide had no effect on the meal-induced changes in blood glucose concentrations. In conclusion, glipizide had the ability to cause an absolute potentiation of beta 2-adrenoceptor-stimulated and meal-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The influence of multiple dosing and age on the pharmacokinetics and pharmacodynamics of glipizide in patients with type II diabetes mellitus.

STUDY OBJECTIVES: To determine the pharmacokinetics and pharmacodynamics of glipizide after a single dose and 12 weeks of dosing in patients with type II diabetes mellitus, and evaluate the influence of aging. DESIGN: Comparison of single and multiple doses of glipizide. SETTING: University-affiliated outpatient internal medicine clinic and diabetes care unit. PATIENTS: Twenty patients (11 men, 9 women, mean age 55.2 +/- 9.9 yrs) with type II diabetes mellitus who were currently receiving oral hypoglycemic agents or were hyperglycemic with diet. INTERVENTIONS: A 24-hour pharmacokinetic evaluation of glipizide was assessed after a 5-mg dose at the start of therapy and after 12 weeks of therapy. Pharmacokinetic parameters were assessed using compartmental population analysis techniques. Glipizide pharmacodynamic evaluation was assessed by serum glucose, insulin, and C-peptide responses during a 4-hour Sustacal tolerance test performed at baseline before instituting glipizide therapy, with the first 5-mg dose, and at week 12 of therapy. Glipizide dosages were titrated to a targeted goal of fasting plasma glucose of 7.8 mmol/L or less or to reach maximum daily doses of 40 mg. MEASUREMENTS AND MAIN RESULTS: No significant differences in time to peak concentration, apparent volumes of distribution for the central and peripheral compartments, apparent oral clearance from the central compartment, distributional clearance between the central and peripheral compartments, or terminal elimination half-life were observed with a single dose and long-term dosing. The mean +/- SD terminal elimination half-lives were 9.67 +/- 5.6 and 9.35 +/- 4.6 hours after a single dose and 12 weeks, respectively. Fasting plasma glucose concentrations decreased from 12.3 +/- 3.6 mmol/L before the first dose of glipizide to 9.2 +/- 1.7 mmol/L after 12 weeks of treatment. The values for area under the serum concentration-time curve from zero to 4 hours for glucose (AUC0-4.glucose) were significantly reduced at week 12 (baseline 49.8 +/- 15.6, week 12 37.8 +/- 9.8 mmol/L/hr). Glipizide provoked an increase in serum insulin and C-peptide concentrations (AUC0-4.insulin: baseline 698 +/- 327, single dose 954 +/- 461, long-term dosing 945 +/- 600 pmol/L/hr). No significant change in insulin response was observed between single and multiple doses. No age-related differences in the pharmacokinetic parameters or the pharmacodynamic responses of glipizide were observed. CONCLUSIONS: Long-term dosing and aging have little effect on the pharmacokinetic profile of glipizide. In addition, glipizide stimulates insulin secretion to a similar extent following glucose challenge after a single dose and long-term administration.

Adult↗
PubMed1994

Glipizide-induced prevention of diabetes and autoimmune events in the BB rat.

To determine whether glipizide, a sulfonylurea, can prevent diabetes in the diabetic-prone BB rat model, rats were studied from 35 to 240 days of age. Treated animals received oral glipizide (10 or 100 mg/kg/day) from 35 to 200 days of age, and control rats received oral placebo. From 80 to 135 days of age at both drug doses, glipizide decreased the incidence of diabetes, thus delaying disease onset (P < 0.02). At the higher dose of glipizide, a diabetes preventive effect was observed (P < 0.025). There were no significant differences in body weights between the treated and control groups. At 240 days, i.e. 40 days after stopping glipizide and placebo treatments, diabetes incidence remained stable in the two groups; thus the effect of glipizide persisted after discontinuation of the drug. Serum glucose and insulin levels measured at 90 and 200 days did not reveal differences between the glipizide treated and control groups. To determine whether the sulfonylurea affected autoimmune events, the prevalence and severity of islet inflammation were examined. In glipizide-treated BB rats at 240 days, only 44% of rats had islet inflammation compared to 86% in the control group (P < 0.01). At both 90 and 240 days the severity of islet inflammation was decreased in the glipizide treatment groups compared with the control groups (P < 0.01). These data indicate that glipizide (a) prevents diabetes in the diabetic-prone BB rat strain, (b) decreases the prevalence and severity of islet inflammation even after drug withdrawal and (c) may dampen autoimmune events leading to diabetes onset.

Age Factors↗
PubMed2004

Simultaneous determination of glipizide and rosiglitazone unbound drug concentrations in plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry.

Glipizide and rosiglitazone are widely used to treat Type 2 diabetes. In order to investigate drug-drug protein binding interaction between glipizide and rosiglitazone, a method was developed and validated for simultaneously determining the free (unbound) fraction of glipizide and rosiglitazone in plasma employing equilibrium dialysis for the separation of free drug and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantitation. Post-dialysis human plasma or buffer samples of 0.2 ml were extracted using a liquid-liquid extraction procedure and analyzed by a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a Zorbax SB-Phenyl column, ionized using an atmospheric pressure electrospray ionization source and analyzed in positive ion mode with multiple reaction monitoring. The ion transitions monitored were m/z 446-->321 for glipizide, m/z 358-->135 for rosiglitazone, and m/z 271-->155 for tolbutamide (internal standard, IS). The chromatographic run time was 5 min per injection, with retention times of 2.3, 3.4 and 2.3 min for glipizide, rosiglitazone and IS, respectively. The calibration curves of glipizide and rosiglitazone were over the range of 1-2000 ng/ml (r(2)>0.9969) in the combined matrix of human plasma and isotonic sodium phosphate buffer (1:1, v/v). The inter-assay precision and accuracy of the quality control samples were <10.9% of coefficient of variability and >93.5% and 94.5% of nominal concentration for glipizide and rosiglitazone, respectively. The lower limit of quantitation of both glipizide and rosiglitazone was 1.0 ng/ml. Both glipizide and rosiglitazone bound to plasma protein extensively (>99% bound). Glipizide and rosiglitazone free fraction averaged 0.678+/-0.071 and 0.389+/-0.061%, respectively, at plasma concentration of 1000 ng/ml. This developed method proves reproducible and sensitive and its application to clinical samples is also reported.

Chromatography, High Pressure Liquid↗
PubMed1983

Pharmacokinetics and pharmacodynamics of glipizide in healthy volunteers.

Single doses of 14C-glipizide were given intravenously (1 mg/4.7 microCi) and orally (5 mg/8.0 microCi) to six healthy volunteers in a crossover study to investigate both pharmacokinetics and effects of glipizide. Based on recoveries of total 14C in urine the gastrointestinal absorption of glipizide was complete. The extent of first-pass metabolism averaged 4.8 +/- 0.04% (SE) of the dose. The pharmacokinetics of i.v. glipizide could be described by a two-compartment open model. The volume of the central compartment was 4.25 +/- 0.25 l and the steady-state volume of distribution averaged 11.7 +/- 1.1 l. Glipizide concentrations in red cells and saliva were only 4% and 1%, respectively, of the concentrations in plasma. The half-life of glipizide elimination averaged 3.3 h both after i.v. and p.o. administration. The total plasma clearance of glipizide was 42.2 +/- 5.4 ml/min, whereas that of protein unbound fraction was 1350 +/- 130 ml/min. Renal clearance was dependent on urinary pH, but on the average it contributed to the total clearance only by 5%. About 17% of the i.v. dose was found in the feces. Intravenous glipizide caused a rapid increase (peak at 6 min, about four-fold) in plasma insulin lasting for 30 min. Plasma glucagon showed an almost simultaneous decrease. These responses were followed by a more sustained decrease in plasma glucose. After oral administration of glipizide the maximal effects on plasma insulin and glucose were seen before the peak concentrations of glipizide in plasma.

Administration, Oral↗
PubMedDate not supplied

Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of glyburide and glipizide, two second-generation oral sulfonylurea hypoglycemic agents, are reviewed. Glyburide and glipizide are well absorbed after oral administration. The absorption of glipizide is delayed by food; in contrast, glyburide absorption does not seem to be affected by administration with meals. Both drugs are extensively metabolized by the liver. A two-compartment open model adequately describes the pharmacokinetics of these drugs. The apparent elimination half-life of glyburide in oral dosage forms available in the United States ranges from 7 to 10 hours. Glipizide has a terminal elimination half-life of 2-7 hours. The effects of renal and hepatic disease on the pharmacokinetics of glyburide and glipizide have not been well studied. Based on controlled, comparative studies in patients with new-onset, diet-failed, Type II diabetes, glyburide appears to be at least as effective as chlorpropamide and tolazamide in controlling blood glucose. Glipizide has shown efficacy comparable to or greater than that of chlorpropamide and tolbutamide. Glyburide and glipizide appear to be comparable in terms of their ability to control fasting blood glucose in Type II diabetics. The recommended initial dosage of glyburide in newly diagnosed Type II diabetics is 2.5-5 mg once daily. For glipizide, the initial dosage should be 5 mg once daily. Elderly or debilitated patients and those with renal or hepatic impairment should be started on lower dosages initially. Glyburide and glipizide have adverse effects that are similar to those observed with the first-generation oral hypoglycemic agents. Glyburide and glipizide do not appear to offer major therapeutic advantages over first-generation oral sulfonylurea hypoglycemic agents. However, they may represent therapeutic alternatives for some patients who do not respond satisfactorily to other sulfonylureas.

Chemical Phenomena↗
PubMed1998

Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients.

BACKGROUND: Glipizide is an oral antidiabetic drug that has been used in the treatment of post-transplant diabetes mellitus (PTDM). However, a published case report has indicated a possible interaction of glipizide with cyclosporine (CsA) pharmacokinetics in two renal transplant (tx) patients. The aim of this open prospective study was to investigate whether glipizide interacts with CsA pharmacokinetics in renal tx patients with PTDM. METHODS: Eleven renal tx patients (29-74 years of age) with PTDM who received Sandimmun Neoral as part of their immunosuppressive therapy were investigated. No patients had suffered any significant rise in serum creatinine (20%) from any cause over the last 2 wk before the study. Mean S-creatinine was 137 mumol/L (87-220). The mean CsA dose and whole blood concentration remained unchanged during the study. CsA whole blood concentrations were monitored over 12 h in all patients in random order, both on and off glipizide treatment. Blood samples were drawn immediately before the morning dose of CsA was given (trough) and 0.5, 1, 1.5, 2, 3, 4, 6 and 12 h after administration. RESULTS: Whole blood trough CsA concentration was not altered by glipizide treatment, 256 +/- 76 micrograms/L off and 242 +/- 73 micrograms/L (mean +/- SD) with glipizide coadministration. The area under the curve (AUC) and terminal half-life of CsA remained unchanged with glipizide treatment: 6391 +/- 1483 micrograms/L per h and 7.3 +/- 1.5 h without; and 6279 +/- 1601 micrograms/L per h and 7.1 +/- 1.8 h with glipizide, respectively. No change in the CsA peak concentration (Cmax) was observed: 1507 +/- 406 micrograms/L without and 1469 +/- 538 micrograms/L with glipizide coadministration. CONCLUSION: CsA pharmacokinetics is not significantly altered by glipizide coadministration.

Adult↗
PubMed2001

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS: Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). CONCLUSIONS: Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

Adult↗
PubMed1990

Combination of insulin with glipizide increases peripheral glucose disposal in secondary failure type 2 diabetic patients.

Twenty Type 2 diabetic patients, recently converted to insulin because of inadequate control on oral hypoglycaemic agents, were studied. Endogenous insulin reserve was measured by glucagon stimulation, and insulin-mediated peripheral glucose disposal by a hyperglycaemic (11 mmol l-1) clamp, measurements being repeated after 8 weeks of glipizide or placebo therapy in addition to the patients' usual insulin. The study was randomized and double blind. Fasting and stimulated C-peptide levels did not change on glipizide or placebo. Insulin-mediated glucose disposal rose from 2.5 (1.5-8.0) (median (range] to 4.2 (2.3-8.4) mg kg-1 min-1 in the glipizide group (n = 9, p less than 0.01), but did not change in the placebo group. Glycosylated haemoglobin did not change in either group, but median fasting plasma glucose fell from 10.6 (6.1-15.1) to 9.0 (6.4-11.2) mmol l-1 in the glipizide group (p less than 0.02). Fasting insulin rose on glipizide from 10.1 (4.0-23.2) to 13.0 (6.4-33.8) mU l-1 (p less than 0.02). Insulin dosage fell in the glipizide group from 36 to 26 U day-1, as 4 patients experienced hypoglycaemic symptoms. HDL-Cholesterol fell in all patients on glipizide, from 0.94 (0.79-2.13) to 0.79 (0.62-1.95) mmol l-1 (p less than 0.01). Combination of insulin with the sulphonylurea glipizide in secondary failure Type 2 diabetic patients leads to increased insulin-mediated peripheral glucose disposal. Glipizide may have an adverse effect on HDL-cholesterol, which is unrelated to change in diabetic control.

Aged↗
PubMed1981

Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.

Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fasting euglycemia was held constant by the glucose clamp technique and averaged 99% basal glucose in all studies. Ra and Rd were determined from infusion of [3-(3)H]glucose, begun 90 min prior to insulin infusion. 10 mg of the sulfonylurea glipizide, was given daily to the test animals for the 10 to 20 d following appropriate control studies, then was withheld for 24 h, and the dogs were restudied. Glipizide treatment did not significantly alter basal glucose turnover, Ra, mean glucose values, or mean insulin levels as determined by radioimmunoassay. Increase in Rd above basal glucose turnover in response to insulin (delta Rd) was significantly (P less than 0.05) increased by glipizide treatment at both insulin dosage levels (paired analysis). At 1.0 mU/kg per min insulin, delta Rd rose from 2.6 mg/kg per min before glipizide to 6.5 mg/kg per min after glipizide treatment. At 0.5 mU/kg per min insulin, delta Rd went from 1.1 mg/kg per min before glipizide to 2.2 mg/kg per min after glipizide treatment. Glipizide treatment doubled the effects of insulin on Rd, while showing no significant effect upon insulin suppression of Ra. We conclude that a significant extrapancreatic chronic action of glipizide lies in its ability to selectively potentiate Rd.

Animals↗
PubMed2006

Bioavailability of immediate- and extended-release formulations of glipizide in healthy male volunteers.

BACKGROUND AND OBJECTIVE: An extended-release glipizide formulation using a hydrophilic matrix system containing hydrophilic polymers has been developed for use in diabetes mellitus. This study compared the pharmacokinetic parameters of immediate- and extended-release formulations of glipizide 5mg in healthy male volunteers. METHODS: In a single-dose, four-period, four-treatment, Latin-square crossover study, the bioavailability of immediate-release glipizide 5mg (Glynase) [GL], extended-release glipizide 5mg (Glynase) XL [GLXL], Glucotrol XL [GTXL], and the new formulation developed in our laboratory [GLPF]) was compared. Plasma glipizide levels of the four formulations were determined at different time intervals, and pharmacokinetic parameters were analysed using a two-compartment body model. RESULTS: The mean peak plasma concentration (C(max)) of the immediate-release formulation (523+/-60 ng/mL) was significantly higher (p<0.05) than those of the three extended-release formulations (403+/-24, 349+/-37 and 426+/-55 ng/mL for GLXL, GTXL and GLPF, respectively). Mean time to reach C(max) was 1.83+/-0.3 hours for GL, 4.41+/-1.2 hours for GLXL, 3.21+/-0.8 hours for GTXL and 3.24+/-0.4 hours for GLPF. The order of magnitude of area under the plasma concentration-time curve was GTXL (5591 ng . h/mL)>GLXL (4,771 ng . h/mL)>GLPF (4,537 ng . h/mL)>GL (1,897 ng . h/mL). The mean residence time was 3.14+/-0.59 hours for GL, 8.26+/-0.81 hours for GLXL, 9.70+/-2.70 hours for GTXL and 7.87+/-1.93 hours for GLPF. Extended-release glipizide formulations maintained effective plasma drug concentrations for approximately 24 hours. Plasma levels of glipizide fluctuated less with GTXL than with the other two extended-release formulations. CONCLUSION: The newly developed formulation (GLPF) maintained effective levels of glipizide for a period of more than 20 hours, with quicker onset of action than the other two formulations. This formulation may be more economical than glipizide GITS.

Adolescent↗
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↗