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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

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

[Experimental study of glipizide. A comparison with other hypoglycemic sulfonamides (author's transl)].

Glipizide is a new hypoglycaemic sulphonylurea. In this work we have studied experimentally the hypoglycaemic activity of this drug, its insulin secretory effect and its action on the development of the islets of Langerhans. Studies in the dog: In the normal conscious dog the hypoglycaemic effect of the drug was studied when increasing doses (0,03 mg/kg, 0,05 mg/kg, 0,07 mg/kg and 0,09 mg/kg) were injected intravenously. The hypoglycaemic effect of the drug occurred rapidly, reaching a maximum in about 30 minutes. The relative potency of glipizide was determined in comparison with tolbutamide. Under our experimental conditions, glipizide proved to be on average 99 times more active than tolbutamide when the doses were evaruated by weight; when the doses were expressed in moles it was 163 times more active. Plasma insulin levels manifested an increase at the first minute. This rose rapidly to a maximum at 5 to 15 minutes after the injection. Following this, insulinemia decreased and the values recorded at 60 minutes were about the same as the starting values. There is a linear relation between the logarithm of the dose and the area under the insulin curve measured for the first sixty minutes. After oral administration to the normal dog, glipizide (081 mg/kg and 1mg/kg) provoked a hypoglycemia manifested after a 30 to 60 minutes latent period. With the dose of 1 mg/kg the maximal effect on blood glucose level was reached between 1,30 and 3 hours, depending on the animal. Plasma insulin levels also increased after a latent period which varied from one animal to another. The dogs presenting the earliest increase in insulinemia were those in which glycemia drops most rapidly. Comparison with other sulfonamides (glibenclamide, glisoxepide and tolbutamide) showed that the hypoglycemic action of glipzide was very similar to that of glisoxepide and that it occurred much earlier than with glibenclamide. The insulin secretory effect of glipizide also occurred much earlier than that of glibenclamide, manifesting itself as early as that of glisoxepide and tolbutamide. Studies on the isolated rat pancreas: On the isolated rat pancreas perfused with Krebs-Ringer solution containing glucose (1,5 g/l), glipizide (10 mug/I) considerably increased the amount of secreted insulin. The stimulation of insulin secretion occurred rapidly and persisted powerfully during the entire duration of the infusion. It faded out progressively after stopping the infusion and the secretion remained higher than the control secretion during the following 45 minutes of the experiment. A concentration as low as 0,5 mug/I provoked a distinct increase of insulin secretion. Studies on the development of the islets of langerhans in the mouse: The prolonged administration of glipizide (100 mg/kg daily for 35 days) increased the "insular index", which is directly proportional to the islet weight, by 27%. Therefore this product possesses betacytotrophic activity...

Administration, Oral

Glyburide versus glipizide in the treatment of patients with non-insulin-dependent diabetes mellitus.

Thirty-four adults with non-insulin-dependent diabetes mellitus were randomly assigned to receive either oral glyburide or oral glipizide in a multicenter comparative trial. Fasting blood glucose and hemoglobin A1c (HbA1c) were assessed at the beginning of the titration phase, the beginning of maintenance therapy, and the end of maintenance therapy. Maintenance therapy lasted approximately 3 months. The initial mean total dose of glyburide (5.4 mg) was significantly lower than that of glipizide (10.6 mg) (P = 0.04) and remained significantly lower at the beginning of maintenance therapy (7.8 mg versus 15.3 mg; P < 0.01) and at the end of the trial (10 mg versus 16.8 mg; P = 0.05). Although significant differences were not detected for fasting blood glucose or HbA1c, patients received higher total doses of glipizide compared with glyburide at the middle and final evaluations to maintain the fasting blood glucose between 3.9 and 10 mmol/L and HbA1c at < 9%. No serious adverse reactions were observed in any patient. These results indicate that doses of glipizide required to maintain blood glucose between 3.9 and 10 mmol/L and HbA1c at < 9% increased over time. Seventy-five percent of patients receiving glyburide were controlled with once-daily dosing compared with 29.4% of those treated with glipizide. Both glyburide and glipizide provide safe and effective treatment for patients with non-insulin-dependent diabetes mellitus, but more patients will benefit from once-daily therapy with glyburide.

Diabetes Mellitus, Type 2

Clinical evaluation of a new sulfonylurea in maturity onset diabetes - glipizide (K-4024).

Glipizide, a new low dose sulfonylurea, was evaluated for its efficacy and toxicity in a double-blind controlled study. Forty adult-onset diabetics were treated with either chlorpropamide or glipizide. In ten out of twenty patients "excellent" to "good" control of hyperglycemia was achieved with glipizide and two patients evidenced "fair" control. In nine out of eighteen patients "excellent" to "good" control was achieved with chlorpropamide. Eight of the sixteen patients who were primary or secondary failures on the two drugs responded to glipizide and phenformin combination with "excellent" to "good" control. No therapeutic advantage was found in giving more than 25 mg/day glipizide in ten patients. Toxicity was low and side effects were uncommon over a period of 26 months.

Adult

Glibenclamide and glipizide in maturity onset diabetes. A double-blind cross-over study.

The effects of glibenclamide and glipizide on the concentrations of S-glucose, S-insulin and S-lipids and on the 24-hour urinary glucose excretion were studied in 37 patients with maturity onset diabetes. A double-blind, cross over double-dummy technique was used. The fasting S-insulin concentration was higher during glibenclamide therapy, while the increase in insulin concentration one hour postprandially was stronger during glipizide therapy, supporting the concept that glibenclamide has a more prolonged and glipizide a more fast-acting effect on insulin secretion. The S-glucose concentration was lower in the fasting state as well as one hour postprandially during glibenclamide therapy which, together with a lower 24-hour urinary glucose excretion, indicates that glibenclamide has a stronger blood glucose-lowering effect. Although statistically significant, the differences were marginal from a clinical point of view. The lipid levels remained unchanged.

Aged

Glipizide in the treatment of maturity-onset diabetes: a multi-centre, out-patient study.

A multi-centre clinical assessment was carried out in 592 diabetic patients to study the efficacy and tolerance of glipizide under normal out-patient conditions. Of the total group, 347 patients were maturity-onset diabetics who had received no previous treatment or only dietary control. The other 245 patients had previously received treatment with other hypoglycaemic agents, including insulin in 23 cases. Mean initial dosage was 7.5 mg glipizide per day and this increased over the 3-month period of the study to 10.1 mg in the total group (9.3 mg in new patients). Mean post-prandial blood glucose levels and glycosuria fell rapidly during the first week and then continued to decrease slowly. Changes in mean body weight were somewhat erratic during the trial and at 12 weeks there was an apparent mean increase of 1 kg. After allowing for dropouts, analysis of the results showed that 96.7% of the new patient group and 90.5% of the total group were satisfactorily controlled and maintained on glipizide. Patient tolerance was good, and only 28 (4.7%) patients complained of side-effects, almost half of which related to mild, transient hypoglycaemia.

Adult

Glipizide ('Glibenese') in maturity-onset diabetes mellitus.

A clinical evaluation was carried out in 19 maturity-onset diabetics to assess the effectiveness of glipizide in the treatment of newly diagnosed patients (11) not responding to diet alone and of patients (8) who had been inadequately controlled on other oral antidiabetic agents. Patients were studied over a period of 6 months. All of the 11 newly diagnosed patients were adequately controlled with glipizide in a dose of 5 to 15 mg/day (mean 9.6 +/- 3.7 mg/day), as were 5 of the 8 previously treated patients with a dose of 10 to 25 mg/day (mean 18 +/- 6.7 mg/day). None of the patients became hypoglycaemic nor did the blood sugar levels indicate hypoglycaemia in the fasting state. Serum triglyceride levels did not change significantly during glipizide therapy, neither did the patients' weight. No side-effects were reported.

Aged

Glipizide: a review of its pharmacological properties and therapeutic use.

Glipizide is a 'second generation' oral hypoglycaemic agent similar in potency to glibenclamide. It is completely absorbed after oral administration and has a rapid onset of action, but the duration of its hypoglycaemic effect is shorter than that of glibenclamide. It is rapidly metabolised to inactive metabolites which are excreted in the urine. Therapeutic trials have shown the efficacy of glipizide in maturity onset diabetes mellitus to be comparable with that of glibenclamide and chlorpropamide in newly diagnosed patients unresponsive to diet as well as in patients previously treated with oral hypoglycaemic drugs. Glipizide is well tolerated, but careful adjustment of dosage and attention to diet may be needed to avoid hypoglycaemic symptoms a few hours after a single daily dose.

Animals

Improvement of glucose tolerance by minimal doses of glipizide in obese subjects with different degrees of glucose intolerance.

Obesity and impaired glucose tolerance (IGT) are risk factors for non insulin dependent diabetes mellitus (NIDDM) and for ischemic heart disease. Long term treatment of IGT subjects with diet and tolbutamide prevents progression of IGT to NIDDM. We have evaluated the lowest dose of glipizide, a second-generation sulfonylurea, able to improve glucose tolerance in response to oral glucose in 31 obese subjects, 12 with NIDDM, 9 with IGT and 10 with normal glucose tolerance (NGT). All subjects underwent four OGTTs, preceded by placebo and by different doses of glipizide (0.5, 1.0, 2.5 mg). Glucose tolerance was progressively improved by increasing glipizide doses in all groups, probably by peripheral mechanism and by enhanced insulin release.

Blood Glucose

[The effect of Glipizide on the blood glucose and insulin in non-ketotic diabetes mellitus (author's transl)].

9 patients suffering from non-ketotic diabetes were treated for 7 days with glipizide, a sulphonylurea derivative. A decrease in blood glucose level was observed in 6 patients during the course of the day, accompanied by an increase in immunoreactive insulin during the first half of the day and an increase in the insulinogenic index. In one patient with insulinopenic diabetes glipizide had only a very small effect on the blood glucose and insulin concentration. 2 patients suffering from insulin resistance caused by type IV hyperlipoproteinanemia and obesity showed an increase in insulin, but no decrease in blood glucose concentration. These results are a further indication that sulphonylurea agents should be administered only in the case of certain specific types of diabetes, because no therapeutic response can be expected in diabetes caused by insulinopenia and insulin resistance.

Adult

A clinical trial with glipizide - a relative new sulphonylurea.

Glipizide is a relatively new sulphonylurea- antidiabetic agent. 24 maturity-onset diabetics were studied to determine the dosage required to produce adequate control and the safety and tolerance of the drug. It was concluded that glipizide is a safe and potent anti-diabetic agent and a suitable alternative in those patients poorly-controlled on standard oral hypoglycaemic drugs.

Adult

Clinical trial with glipizide in uncomplicated maturity onset diabetes mellitus.

A clinical trial with a new hypoglycaemic drug glipizide was carried out for an average period of 7 months, on 51 non-insulin independent adult diabetics attending the out-patients clinic of the Diabetic Association of Pakistan, Karachi. Forty five patients were satisfactorily controlled on glipizide. No toxic side effects were observed and the drug was well tolerated.

Adult

A controlled study of the hypoglycemic and insulinopoietic effect of glipizide and glibenclamide in non-diabetic human subjects.

The authors studied in 12 non-diabetic women the effect on blood glucose and IRI of 2.5 mg of N-(4-[2-5-methylpyrazine-2-carboxamido)-ethyl]-benzenesulphonyl)-N'-cyclohexyl-urea (glipizide) and N-4[2-5(-chloro-2-methoxy-benzamido)-ethyl]-phenylsulphonyl-N'-cyclohexyl-urea (glibenclamide) given orally as a single dose according to a single blind crossover experimental design. After glipidide the effect on blood glucose was prompter and Immuno Reactive Insulin (IRI) levels higher. These results are in agreement with kinetic studies showing rapid and practically complete absorption of the product from the gastrointestinal tract. This fact together with the fast excretion of the drug and metabolites renders delayed hypoglycemic reactions very unlikely after administration of glipizide.

Adult

[Duration of effective hypoglycaemic action of glipizide given once daily (author's transl)].

The clinically effective duration of blood glucose lowering action of a new hypoglycaemic sulphonylurea, glipizide, given in single before breakfast dosage (up to 20 mg) has been studied in 20 apparently insulin-independent diabetics. All, on diet only, had persistent overnight 1-2% glycosuria, fasting glycaemia in excess of 150 mg/100ml, random mid-morning glycaemia of at least 250 mg/100ml and associated clinical symptoms. Eighteen were satisfactorily controlled over the observation period of six months by single daily dosage (mean 10 mg daily); in addition considerable improvement in glucose tolerance occurred. Complementary in-patients indicated that, within the range of dosage studied, there was no therapeutic advantage in taking glipizide twice daily.

Administration, Oral

Comparison of the pharmacokinetics of glipizide and glibenclamide in man.

Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.

Administration, Oral

Insulin in portal, hepatic and peripheral venous blood after glucose, tolbutamide and glipizide stimulation. Indication of insulin release from peripheral tissues.

Insulin in portal, hepatic and/or peripheral venous blood was determined in 16 patients admitted to a surgical ward for various diseases. Portal venous blood was obtained via a catheter introduced into the portal vein either through the umbilical vein remnant or transhepatically. Four subjects were given a peroral load of glucose, followed after 60 min by i.v. tolbutamide. In simultaneous blood samples, two of these subjects showed higher insulin concentrations in peripheral venous blood than in portal venous blood. Twelve subjects were given i.v. glipizide. In one subject blood samples were drawn from the portal vein, a hepatic vein and a peripheral vein and in six subjects from the portal vein and a hepatic vein. Two subjects showed higher insulin concentrations in peripheral venous blood than in portal venous blood. The mean peripheral insulin response (six subjects) was of the same magnitude as the mean hepatic insulin response (six subjects). It is suggested that these findings reflect a release of previously bound insulin from peripheral tissues.

Adult