Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Glipizide: a review of its pharmacological properties and therapeutic use. 38

Intensive insulin treatment, when combined with sulfonylurea drugs, may enhance remissions in new-onset type I diabetic patients. These clinical data suggest that sulfonylurea drugs may have immunosuppressive actions in addition to insulin secretory and sensitivity actions. Thus, studies were conducted in humans to determine if glipizide was immunomodulatory in vitro. Five, 10, and 15 micrograms/mL of phytohemagglutinin (PHA) and concanavalin A (Con A), and 0.5, 1.0, and 1.5 micrograms/mL of pokeweed mitogen (PWM) were incubated with normal human peripheral blood mononuclear cells. Maximum stimulatory indices were 52, 39, and 30 for PHA, Con A, and PWM, respectively. Additional incubations were performed in the presence of 1, 10(1), 10(2), 10(3), 10(4), and 10(5) ng/mL glipizide. Glipizide concentrations inhibiting mitogen stimulation approximately 50% (P less than .01 v nonglipizide control) were 1.0 ng/mL for PWM, 10 ng/mL for Con A, and 10(4) ng/mL for PHA. At higher glipizide levels, inhibition was 90% to 100%. To determine if glipizide immunomodulates diabetes-associated reactions, bio-breeding (BB) diabetic rat splenic macrophage-mediated islet killing was studied. Glipizide at 10(3) ng/mL inhibited islet killing by 60% (P less than .001). These preliminary data suggest that glipizide may have immunomodulatory actions not previously appreciated, and may be related to this drug's putative action in islet cell restoration.
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PMID:Glipizide-induced immunomodulation: inhibition of human mononuclear cell stimulation and macrophage-mediated islet cell killing in the BB rat. 155 50

To assess the effect of Glipizide on glycaemic control and peripheral insulin sensitivity, 9 type 1 (insulin dependent) diabetic patients with normal BMI, mean age 42.1 +/- 11.0 years, diabetes duration 16.3 +/- 9.2 years were studied. They were treated by continuous subcutaneous insulin infusion for a mean duration of 32.2 +/- 11.0 months, they were in good glycaemic control (mean HbA1 7.9 +/- 1.2%, upper limit of normal value 7.5%). In a double blind randomized control study they were successively allocated for a three month period to 15 mg of Glipizide daily or a Placebo. At the end of each period the following parameters were recorded: HbA1, mean plasma glucose levels, daily insulin dosage: basal rate and pre prandial bolus, peripheral insulin sensitivity assessed by euglycaemic hyperinsulinic clamp technique, the addition of Glipizide did not induce any statistically significant modification of HbA1, glycaemic values, and daily insulin dosage: basal rate 18.2 +/- 8.7 vs. 17.9 +/- 7.3 IU/24 hours and pre prandial bolus 18.6 +/- 7.0 vs 17.6 +/- 6.3 IU/24 hours. During the glucose clamp, glucose uptake was similar under Glipizide or Placebo with the 3 levels of insulin infused. These results suggest that in type 1 diabetic patients the addition of Glipizide to insulin therapy does not alter glycaemic control and peripheral insulin sensitivity.
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PMID:[Effect of glipizide on glycemic control and peripheral insulin sensitivity in type 1 diabetics]. 219 93

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.
Diabetes Care
PMID:Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment. 312 84

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular disease.
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PMID:Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus. A weight reduction-exercise-oral agent approach. 330 4

55 patients with non-insulin-dependent diabetes mellitus were treated with the new oral drug Minidiab. In 58.2% of the patients the carbohydrate metabolism was influenced. No relation between the immunoreactive insulin increase and the effect of the treatment was found. An extrapancreatic action of the drug is suggested as its hypoglycemic activity.
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PMID:[Our experience in treating diabetes mellitus with the preparation Minidiab]. 341 5

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)
Diabetes Res 1986 Jul
PMID:Effects of glipizide on various consecutive insulin secretory stimulations in patients with type 2 diabetes. 353 May 92

Sulfonylureas seem to have similar mechanisms of action, including an acceleration and increase of insulin secretion, an increase of the systemic availability of insulin, and probably indirectly, an increase of insulin action. Sulfonylureas may postpone the development of impaired glucose tolerance (IGT) to manifest non-insulin-dependent diabetes mellitus (NIDDM), and all NIDDM subjects should benefit from sulfonylurea treatment except those in whom insulin secretion has been attenuated. The most effective use is the combination of diet restriction and sulfonylurea introduced in NIDDM subjects soon after transition from IGT to NIDDM. A simple screening procedure has been devised to find the subjects at this early stage. Newer sulfonylureas, such as glipizide and glyburide, are more potent than the older ones, such as tolbutamide and chlorpropamide. During chronic treatment, glipizide and glyburide seem to be equally effective in reducing blood glucose levels, and they do so without causing a chronic elevation of insulin secretion, signifying that they do not increase the risk of pancreatic B cell exhaustion. Glipizide has rapid and complete absorption, as well as a rapid distribution and elimination. This may explain why it is less liable than other sulfonylureas to provoke long-lasting hypoglycemia, which is the major danger when using sulfonylureas. Despite its rapid elimination, 7.5 to 15 mg glipizide can be administered once daily without loss of therapeutic efficacy. This may be due in part to enterohepatic recirculation of the drug in response to meals. The therapeutic efficacy is increased if glipizide is received half an hour before breakfast.
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PMID:Clinical pharmacology of sulfonylureas. 354 16

While the prevention of acute metabolic decompensation is no longer a serious problem in treating patients with non-insulin-dependent diabetes mellitus (NIDDM), target organ complications can have serious consequences, including blindness, renal failure, neuropathy, amputation, coronary artery disease, and stroke. The bulk of current evidence suggests that these complications can be minimized or perhaps even avoided by carefully monitoring and controlling the patient's blood glucose levels. Although criteria and standards of control differ widely in various centers, in general acceptable-to-good control in the NIDDM patient would consist of average fasting blood glucose (FBG) levels of less than 140 mg/dL and peak postprandial glucoses of less than 220 to 250 mg/dL. Treatment aimed at attaining these blood glucose levels should begin with dietary management and exercise prescription. General health measurements such as control of blood pressure and avoidance of smoking are especially important in the diabetic patient. When these approaches prove ineffectual, the addition of an oral hypoglycemic agent, preferably a second-generation sulfonylurea is indicated. Glipizide and glyburide are both excellent drug choices, although glyburide may cause hypoglycemia in older patients due to its longer half-life and especially in those with renal insufficiency because of accumulation of biologically active metabolites. In certain well-selected cases, the addition of insulin to oral sulfonylurea therapy may offer improved results over the use of either therapeutic modality alone. The advent of self blood glucose monitoring and periodic glycohemoglobin assessments, now well established in diabetic management, represents a major step forward in the endeavor to optimize standards of blood glucose control in the diabetic population.
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PMID:Monitoring and controlling the patient with non-insulin-dependent diabetes mellitus. 354 18

The current study examines the impact of glipizide, a second-generation sulfonylurea, on diabetes control in patients in whom adequate control was not achieved while receiving treatment with first-generation agents. The interim results of this multicenter study are presented in which patients in whom euglycemia was not achieved based on fasting and two-hour postprandial plasma glucose criteria with first-generation sulfonylureas were given glipizide therapy for 24 weeks. Twenty-three percent of the patients who had only fair results with first-generation sulfonylureas (fasting plasma glucose level of more than 140 mg/dl, postprandial plasma glucose level of more than 175 mg/dl) had good to excellent results with glipizide therapy alone (fasting plasma glucose level of less than 140 mg/dl or less than 115 mg/dl, respectively). Overall, 15.4 percent of patients with fair to poor control using first-generation agents had good to excellent control using glipizide. At least a 25-mg/dl decrease in fasting plasma glucose and postprandial plasma glucose levels was also seen in 47 and 46 percent of patients given treatment with glipizide who had poor control (fasting plasma glucose level of more than 200 mg/dl, postprandial plasma glucose level of more than 235 mg/dl) with first-generation agents. Glipizide was extremely well tolerated, with no significant side effects. Preliminary data indicate that glipizide may provide a significant advantage in terms of safety and efficacy over first-generation agents.
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PMID:Evaluation of first-generation sulfonylureas and glipizide in non-insulin-dependent diabetes mellitus. 363 Nov 18


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