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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 sulfonylurea in which the substitutions on the arylsulfonylurea nucleus are large, relatively nonpolar groups. This chemical change increases the intrinsic hypoglycemic activity of the molecule 100-fold on a weight basis compared to first-generation agents. In addition, the pharmacokinetic properties, spectrum and severity of side effects and metabolism of this agent are somewhat different from those of first-generation sulfonylureas. The most important component of the antidiabetic action of glipizide is its effect in potentiating insulin action. Glipizide-mediated increases in nutrient-stimulated insulin secretion may contribute to its antidiabetic action. The drug is effective in controlling the blood glucose in patients with noninsulin-dependent diabetes mellitus. It is at least as effective as and probably more effective than first-generation sulfonylureas in controlling hyperglycemia in diabetes. Glipizide is relatively free of serious side effects and is contraindicated principally in patients with significant liver or kidney disease.
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PMID:Glipizide: a second-generation sulfonylurea hypoglycemic agent. Pharmacology, pharmacokinetics and clinical use. 392 54

Glipizide, a second-generation sulfonylurea, has potent antidiabetic actions in patients with noninsulin-dependent diabetes mellitus. The effects of glipizide treatment on insulin sensitivity, glucose-mediated insulin secretion, and glucose utilization were measured in newly diagnosed or untreated patients with noninsulin-dependent diabetes mellitus. The data indicate that the antidiabetic action of glipizide is primarily mediated by a potentiation of insulin action and, to a less significant and more variable degree, by an increase in nutrient-mediated insulin secretion. Studies in normal mice and dogs show that glipizide potentiation of insulin action is associated with an increase in plasma membrane insulin receptor number, involves some postreceptor events, and is significantly greater on peripheral uptake of glucose than suppression of hepatic glucose production. The initial event in glipizide action on beta cells appears to be binding to a specific plasma membrane receptor.
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PMID:Mechanism of action of the second-generation sulfonylurea glipizide. 636 67

Glipizide is a "second generation" sulfonylurea compound, and in this study the effects of several months of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism were documented in 23 patients with noninsulin-dependent diabetes mellitus. Mean (+/-SEM) fasting plasma glucose concentration decreased (p less than 0.001) from 264 +/- 12 to 172 +/- 10 mg/dl, and a similar decrement in postprandial glucose concentration was also seen following glipizide therapy. Mean plasma triglyceride concentration was also lower (p less than 0.05) after glipizide treatment and was associated with modest reciprocal changes in plasma cholesterol (lower) and high-density lipoprotein cholesterol (higher) concentrations. Although neither of these latter two effects was statistically significant, the net effect was to lead to a significant (p less than 0.02) increase in the ratio of high-density lipoprotein cholesterol to total cholesterol. Furthermore, significant relationships were noted between the improvement in diabetic control in glipizide-treated patients and lowering of both very low-density lipoprotein-triglyceride (r = 0.69, p less than 0.001) and low-density lipoprotein-cholesterol (r = 0.54, p less than 0.02) concentrations. Finally, glipizide treatment was associated with improvements in both the plasma insulin response to mixed meals and estimates of in vivo insulin-stimulated glucose utilization. Although both of these changes were likely to have contributed to the ability of glipizide to lower plasma glucose concentrations, only the increase in in vivo insulin action correlated with the improvement in diabetic control (r = 0.69, p less than 0.001).
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PMID:Effect of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism in patients with noninsulin-dependent diabetes mellitus. 636 70

The clinical pharmacology of glipizide and other sulfonylureas is briefly reviewed. Reevaluation of the University Group Diabetes Program data suggests that sulfonylureas do not increase cardiovascular mortality. Instead, a long-term study of subjects with impaired glucose tolerance indicates that sulfonylureas reduce the frequency of cardiovascular morbidity and can postpone or even prevent the development of impaired glucose tolerance to manifest diabetes. It is likely that all sulfonylureas have the same principal mechanism(s) of action but that they differ in potency and pharmacokinetics, resulting in considerable clinical differences. Thus, glipizide and glibenclamide (glyburide) are much more potent than tolbutamide and chlorpropamide. Glipizide has the most rapid absorption and onset of action, as well as the shortest half-life and effect-duration; hence the risk of long-lasting hypoglycemia is minute. Glipizide has complete bioavailability, and its blood glucose-lowering effect is improved when it is given before breakfast. Glipizide may be administered once daily without loss of therapeutic efficacy.
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PMID:Clinical pharmacology of glipizide. 642 40

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.
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PMID:Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents. 643 40

The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were examined before and after a minimum of 3 mo treatment. Mean (+/- SEM) fasting plasma glucose level fell from 264 +/- 12 mg/dl to 172 +/- 10 mg/dl (P < 0.001) after glipizide treatment, and this was associated with a fall in total plasma glucose response to a test meal of approximately 35%. Mean (+/- SEM) fasting plasma insulin levels increased slightly from 15 +/- 2 micronU/ml following sulfonylurea treatment, and the total plasma insulin response to the test meal increased by 63%. However, there was no correlation (r = - 0.20) between the increase in plasma insulin response and the fall in plasma glucose levels that occurred as the result of sulfonylurea therapy. Glipizide treatment also led to enhanced in vivo insulin action, whether measured by the insulin clamp technique (P < 0.001) or the insulin suppression test (P< 0.02). Furthermore, in this instance there was a significant correlation (r - 0.69, P < 0.001) between the enhanced insulin action and the improvement on diabetes control. Thus, chronic therapy with glipizide, a new sulfonylurea agent, led to increased in vivo insulin secretion and insulin action. These results lend direct support to the assumption that sulfonylurea compounds have a substantial extrapancreatic effect on glucose homeostasis, and suggest that this effect contributes to the therapeutic efficacy of these drugs.
Diabetes 1982 Apr
PMID:Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus. 675 46

Glipizide, a new sulfonylurea recently introduced for the treatment of diabetes, was studied to check its possible extrapancreatic effects. Rats were given a subcutaneous injection of 1 g/kg glucosamine: this dose caused marked hyperglycemia and a decrease in hepatic glycogen, but does not alter blood insulin levels. Pretreatment with i.v. dose of 37.5 microgram/kg glipizide 1 hour before the glucosamine load, significantly inhibits the hyperglycemia and the decrease of hepatic glycogen. This dose of glipizide does not affect blood sugar levels, although it does induce a transient rise in insulin secretion, which lasts no more than 10 minutes after administration. Since glucosamine was administered 1 hour after the sulfonylurea by which time the interference of insulin was no longer felt, it may be concluded that in the experiment described, glipizide seems to have some other action apart from stimulating insulin secretion.
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PMID:Glipizide and hepatic glycogenolysis. 700 38

The levels of glucose, insulin, and C-peptide in the blood serum were measured in 38 subjects with normal and impaired glucose tolerance whose parents suffered from insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM and NIDDM, respectively) and in 12 normal subjects without hereditary aggravation for diabetes mellitus in order to specify the peculiarities of development of diabetes mellitus of various types. Reliably increased levels of glucose, insulin, and C-peptide on an empty stomach and absence of adequate secretion of insulin and C-peptide in response to stimulation with 5 mg of minidiab, expressed by a later and less manifest release of insulin and C-peptide, were observed in the test group, in contrast to healthy controls. The detected changes augment with the progress of carbohydrate metabolism disorders, being more marked in the subjects whose parents suffered from IDDM. The findings permit a conclusion that function of the insular system is changed during early disorders of carbohydrate metabolism in subjects whose parents suffered from both forms of diabetes mellitus. Minidiab test is recommended to specify the function of the pancreatic insular system.
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PMID:[Minidiab test to assess the functional state of pancreatic beta-cells in the children of diabetics]. 774 43

The purpose of the present study was to determine if the oral hypoglycemic agent glipizide influenced sympathetic outflow in diabetes-prone mice. C57BL/6 (diabetes-prone) and diabetes-resistant (A/J) were treated with saline or glipizide, and sympathetic outflow determined by the fall in organ norepinephrine content after synthesis inhibition with alpha-methyl-para-tyrosine. Sympathetic outflow to the liver and pancreas were slower in Bl/6 mice than in control A/J. Glipizide increased sympathetic outflow to the pancreas in both strains of mice, but did not influence outflow to other organs significantly. The results of this study suggest that glipizide can influence central glucoregulatory mechanisms after peripheral administration.
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PMID:Glipizide stimulates sympathetic outflow in diabetes-prone mice. 786 47

An orally administered sulfonylurea drug, glipizide, was evaluated for treatment of diabetes mellitus. Confirmation of diabetes was based on evidence of appropriate clinical signs, persistent hyperglycemia, and glucosuria. Glipizide (5 mg, PO, q 12 h) was administered to each cat. Sixteen cats were fed a commercial high-fiber diet and 4 cats were fed a commercial low-fiber diet. Insulin was not administered to any cat during the study. Each cat was evaluated 2, 4, 8, and 12 weeks after initiation of treatment. Three clinical responses to glipizide treatment were identified. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period decreased to < 200 mg/dl in 5 of 20 (25%) cats. In these 5 cats, glucosuria was no longer detected and clinical signs resolved by the 4-week reevaluation. Euglycemia was maintained after discontinuing glipizide treatment in 2 of these 5 cats. Glycemic control has been maintained in 2 of 5 of the responding cats for 5 and 7 months of glipizide treatment. One of 5 of the responding cats developed insulin-requiring diabetes mellitus after 6 months of glipizide treatment. Seven of 20 (35%) cats failed to respond to treatment. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period did not change from pretreatment values after 2 +/- 1 months; glucosuria persisted and clinical signs progressively worsened. Insulin treatment was required to establish glycemic control in these 7 cats. Eight of 20 (40%) cats partially responded to glipizide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of an orally administered sulfonylurea, glipizide, for treatment of diabetes mellitus in cats. 822 35


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