Glipizide Gastrointestinal Therapeutic System Research Articles

Chromium Picolinate Supplementation Attenuates Body Weight Gain and Increases Insulin Sensitivity in Subjects With Type 2 Diabetes

Chromium picolinate (CrPic) supplementation has been suggested to improve glycemia, but there are conflicting reports on efficacy. We sought to determine the effect of CrPic on insulin sensitivity, glycemic control, and body composition in subjects with type 2 diabetes. Thirty-seven subjects with type 2 diabetes were evaluated. After baseline, subjects were placed on a sulfonylurea (glipizide gastrointestinal therapeutic system 5 mg/day) with placebo for 3 months. Subjects were then randomized in a double-blind fashion to receive either the sulfonylurea plus placebo (n = 12) or the sulfonylurea plus 1,000 microg Cr as CrPic (n = 17) for 6 months. Body composition, insulin sensitivity, and glycemic control were determined at baseline, end of the 3-month single-blind placebo phase, and end of study. Subjects randomized to sulfonylurea/placebo, as opposed to those randomized to sulfonylurea/CrPic, had a significant increase in body weight (2.2 kg, P < 0.001 vs. 0.9 kg, P = 0.11), percent body fat (1.17%, P < 0.001 vs. 0.12%, P = 0.7), and total abdominal fat (32.5 cm(2), P < 0.05 vs. 12.2 cm(2), P < 0.10) from baseline. Subjects randomized to sulfonylurea/CrPic had significant improvements in insulin sensitivity corrected for fat-free mass (28.8, P < 0.05 vs. 15.9, P = 0.4), GHb (-1.16%, P < 0.005 vs. -0.4%, P = 0.3), and free fatty acids (-0.2 mmol/l, P < 0.001 vs. -0.12 mmol/l, P < 0.03) as opposed to sulfonylurea/placebo. This study demonstrates that CrPic supplementation in subjects with type 2 diabetes who are taking sulfonylurea agents significantly improves insulin sensitivity and glucose control. Further, CrPic supplementation significantly attenuated body weight gain and visceral fat accumulation compared with the placebo group.

The identification of a R201H mutation in KCNJ11, which encodes Kir6.2, and successful transfer to sustained-release sulphonylurea therapy in a subject with neonatal diabetes: evidence for heterogeneity of beta cell function among carriers of the R201H mutation

To the Editor Diabetes caused by severe mutations in beta cell genes is usually diagnosed as neonatal diabetes [1] or MODY [2]. Activating mutations in KCJN11, the gene encoding the ATP-sensitive potassium channel subunit Kir6.2, have been described in very-early-onset diabetes ( A) was found in a single patient. This child was born at 40 weeks’ gestation and weighed 2,450 g. He was diagnosed with diabetes during the third week of life based on a plasma glucose of 35–50 mmol/l, without ketoacidosis, which was measured when he presented with pneumonia and bilateral acute otitis media. The patient was treatedwith insulin, with a dose of 0.7–1.0 U/kg used initially and subsequently decreased. At 9 years, 11 months he weighed 27.5 kg and his daily insulin requirement was 7 U (0.25 U/kg) as a single morning injection of intermediate-acting insulin. Despite little modification to his diet he rarely experienced hyperglycaemia above 11 mmol/l, and had an HbA1c level of 6.6%. These observations suggested endogenous beta cell function, which was confirmed by a fasting plasma C-peptide of 443 pmol/l (glucose 6.7 mmol/l) and an increase in plasma insulin concentration of 70 pmol/l during an IVGTT (Fig. 1). As patients with Kir6.2 diabetes may respond to sulphonylureas, we assessed whether this patient could successfully transfer to sulphonylurea tablets [3, 4]. Glipizide gastrointestinal therapeutic system (GITS), a controlledrelease sulphonylurea, was introduced [5]. A dose of 5 mg was administered for 2 days, then 10 mg; insulin was simultaneously slowly withdrawn over a period of 5 days. As the patient experienced a few mild hypoglycaemic episodes during the first 2 days after the discontinuation of insulin the glipizide GITS dose was decreased to 5 mg. While on this dose, a day profile of his capillary glucose concentrations revealed that they were between 4 and 6 mmol/l; a result confirmed by a 72-h record obtained using a continuous glucose monitoring system (Medtronic, Northridge, CA, USA). The IVGTT was repeated 3 weeks after a stable glipizide dose was achieved. At this time the patient’s fasting glucose level was 5.4mmol/l, and his C-peptide level was 347 pmol/l. T. Klupa and E. L. Edghill contributed equally to this work

Beneficial metabolic effects of chronic glipizide in obese african americans with impaired glucose tolerance: implications for primary prevention of type 2 diabetes

We examined the long-term metabolic effects of glipizide gastrointestinal therapeutic system (GITS), a potent sulfonylurea (SU), in impaired glucose-tolerant (IGT), first-degree relatives of African American patients with type 2 diabetes. To this end, we assessed glucose homeostasis, beta-cell function, insulin sensitivity (Si), and glucose effectiveness (Sg) in patients with IGT before and at yearly intervals for 24 months of GITS or an identical placebo in a randomized, double-blind manner. Eighteen IGT patients were randomized to receive either glipizide GITS (GITS, 5 mg/d, n = 9; mean age, 43.3 ± 8.7 years; mean body mass index [BMI], 32.9 ± 6.3 kg/m 2) or identical placebo (PLAC, n = 9; mean age, 41.5 ± 5.7 years; mean BMI, 39 ± 4.2 kg/m 2) for 24 months. Each of the subjects underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT) at baseline and yearly intervals for 2 years. Si and Sg were determined by Bergman’s minimal model method. The ability of beta cell to compensate for peripheral insulin resistance was calculated as the disposition index (DI). Chronic administration of glipizide GITS attenuated serum glucose responses to oral glucose challenge at 12 and 24 months when compared to baseline (0 months). In contrast, serum glucose levels at fasting and during OGTT tended to increase in the IGT/PLAC group at 12 and 24 months when compared to baseline. Serum insulin ( P < .05 to 0.01) and serum C-peptide levels progressively increased in the GITS group at 12 and 24 months versus 0 months. In contrast, serum insulin and C-peptide responses remained unchanged in the IGT/PLAC group. During FSIGT, chronic GITS was associated with significant improvement in the blunted acute first insulin release in the IGT patients at 12 and 24 months. These parameters remained blunted in the IGT/PLAC group. We found that Si increased in the IGT/GITS group at 12 months ( P < .01) and 24 months( P < .05) versus baseline, but deteriorated in the IGT/PLAC group. Similarly, the DIs significantly ( P < .01) increased following GITS therapy at 12 and 24 months when compared to baseline. In contrast, DI did not change from baseline values in the IGT/PLAC group throughout the study period. Chronic GITS partially restored the ability of beta cells to compensate for peripheral insulin resistance (as assessed by DIs). GITS was well tolerated without any symptoms suggestive of either hypoglycemia or significant weight gain. In summary, long-term chronic glipizde GITS administration improved glucose homeostasis by increasing beta-cell responsiveness to glucose, improving Si, as well as significantly improved DI, but not Sg, in high-risk, obese African Americans with IGT. Our study demonstrated that GITS appears to prime beta cells to intravenous glucose stimulation resulting in restoration of physiologic acute first- and second-phase insulin secretion in African Americans with IGT. We conclude that GITS might be considered as a useful agent in the primary prevention of type 2 diabetes in high-risk, obese African American patients with IGT.

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.

Metabolic effects of chronic glipizide gastrointestinal therapeutic system on serum glucose, insulin secretion, insulin sensitivity, and hepatic insulin extraction in glucose-tolerant, first-degree relatives of African American patients with type 2 diabetes: New insights on mechanisms of action

We examined the long-term metabolic effects of a potent sulfonylurea (SU), glipizide gastrointestinal therapeutic system (glipizide GITS) in normal glucose-tolerant (NGT), first-degree relatives of African American patients with type 2 diabetes in a randomized, placebo-controlled, double-blind manner for 24 months and 6 months after discontinuation of glipizide GITS. Fifty NGT African American first-degree relatives (n = 50)) were randomized to receive either glipizide GITS (GITS, 5 mg/d) or identical placebo (PLAC). The NGT consisted of NGT/GITS (n = 16; mean age, 43.1 ± 8.7years; body mass index [BMI], 34.8 ± 10) and NGT/PLAC (n = 34; 45.5 ± 9.7 years; BMI, 31.3 ± 3.1years). Each of the subjects underwent an oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT) at baseline and at yearly intervals for 2 years. Insulin sensitivity (Si) and glucose effectiveness (Sg) were determined by Bergman's minimal model method. Hepatic insulin extraction (HIE) was calculated as the molar ratio of C-peptide and insulin. The mean fasting serum glucose, insulin, and C-peptide levels in the NGT/GITS were not different from that of the NGT/PLAC. After oral glucose challenge, mean serum glucose responses slightly increased (P = not significant [NS]) at 12 and 24 months in the NGT/GITS group when compared with the baseline, 0 month, but remained unchanged in the NGT/PLAC group. In addition, serum insulin and C-peptide responses significantly increased in the NGT/GITS group, but were unchanged in the NGT/PLAC group at 12 and 24 months versus 0 month. The HIE, during OGTT, decreased by 30% from the baseline (0 month) values in the NGT/ GITS, but remained unchanged in the NGT/PLAC group at 12 and 24 months. Mean Si decreased by 30% from the baseline in the NGT/GITS group by 12 and 24 months, but remained unchanged in the NGT/PLAC group. However, the disposition index (DI) remained normal in the NGT/GITS and the NGT/PLAC groups. The DI data in the NGT/GITS group suggested that β cells maintained the ability to compensate for the lower Si during the chronic GITS administration in our high risk African Americans. Chronic GITS was well tolerated without any symptoms of either hypoglycemia or weight gain in the NGT/IGTS group. After discontinuation of GITS, the altered metabolic parameters significantly improved, returning to baseline values in the NGT/IGTS group in 6 months. In summary, chronic glipizide GITS administration (5 mg/d) was associated with increased β-cell secretion, peripheral hyperinsulinemia, reduced Si, and reduced HIE in glucose-tolerant, first-degree relatives of African American patients with type 2 diabetes. These metabolic changes were reversible within 6 months after discontinuation of glipizide GITS. Our study defines a unique mode of action of glipizide GITS in African Americans at high risk for type 2 diabetes. We conclude that the use of glipizide GITS in the primary prevention of type 2 diabetes in nondiabetic first-degree relatives of patients with type 2 diabetes impaired glucose homeostasis. © 2003 Elsevier Inc. All rights reserved.

Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus.

To assess the short-term direct medical costs and effectiveness associated with achieving recommended glycaemic goals using commonly prescribed first-line oral antihyperglycaemic medications in type 2 diabetes mellitus. A literature-based, decision-tree model was developed to project the number of patients achieving glycosylated haemoglobin values of <7% on oral therapies and the associated costs over a 3-year timeframe. For each first-line strategy, patients could progress to combination therapy using two or more agents prior to the introduction of insulin. The overall cost of treatment included costs (2001/2002 values; US dollars) of comprehensive medical care, laboratory tests, patient education, drug therapy, home glucose monitoring and adverse events. At 3 years, the overall cost of treatment for the various first-line strategies was 6,106 US dollars for glipizide gastrointestinal therapeutic system, 6,727 US dollars for metformin immediate release, 6,826 US dollars for metformin extended release, 7,141 US dollars for glibenclamide (glyburide)/metformin, 7,759 US dollars for rosiglitazone and 9,298 US dollars for repaglinide. Costs of comprehensive routine medical care ranged from approximately 1,538-2,128 US dollars in year 1 and from approximately 952-1,543 US dollars in subsequent years, for controlled and uncontrolled patients, respectively. Adverse events represented <1%, and drug therapies represented approximately 50%, of the overall cost, respectively. Substantial cost differences between the strategies were seen within the first year. Regardless of first-line therapy, patients progressed quickly to combination therapies, with effectiveness among the agents being similar. Short-term costs required to provide comprehensive diabetes care and achieve glycemic goals can be substantial. The model suggests a sulphonylurea strategy may provide similar effectiveness with cost savings over other agents and should be considered when selecting an initial drug therapy in newly diagnosed patients with type 2 diabetes mellitus.

A 'Real-World' Analysis of Persistence on and Adherence to Glipizide GITS, Glipizide IR and Glibenclamide in Managed Care among Patients with Type 2 Diabetes Mellitus.

This study compared persistence on and adherence to therapy with glipizide gastrointestinal therapeutic system (GITS), glipizide immediate release (IR) and glibenclamide (glyburide) in commercially insured patients newly treated for type 2 diabetes mellitus. The objective of the study was to determine if there were differences in persistence and adherence between the three second-generation sulphonylureas. This was a retrospective longitudinal claims data analysis for commercial enrollees in eight independent practice model health plans. Study subjects were 25 years of age or older with a first prescription for a study drug from 1 January 1996 through 31 December 1999. All subjects were newly treated with medication for diabetes mellitus, and were initiated on monotherapy. To be included in the study, subjects had to be continuously enrolled in their health plan 6 months prior to their index claim and at least 30 days following the index claim. Persistence was defined as the total days from the index prescription fill date until termination, switch or augmentation of therapy. Adherence was defined as the ratio of days supplied to total days in the treatment period. The treatment period for the measurement of adherence was defined as the period from index prescription fill date to run-out of days supplied of the last filled prescription for the index drug. Cox proportional hazards analysis was used to compare differences in persistence, and multivariate regression was used to assess differences in adherence. Of the 24 311 subjects, 35% filled a first prescription for glipizide GITS, 15% for glipizide IR, and 50% for glibenclamide. Over one-half of study subjects were male, and the average age was between 51 years for the glipizide GITS cohort and 53 years for the glibenclamide cohort. By the end of the study, 79% of subjects had terminated therapy with their index drug. Cox proportional hazards analysis showed that patients taking glipizide IR were 1.33 times more likely to experience treatment change [95% confidence interval (CI) 1.25 to 1.42], and patients taking glibenclamide were 1.16 times more likely to change therapy (95% CI 1.11 to 1.22) compared with patients taking glipizide GITS in the first 90 days following initiation of therapy. Similar results were found upon subsequent analysis in the 1620 days following the index prescription. The analysis of adherence showed that patients taking glipizide IR or glibenclamide were less adherent to therapy compared with patients taking glipizide GITS (p < 0.001). Glipizide GITS appears to have an advantage in persistence on and adherence to therapy compared with glipizide IR and glibenclamide. These differences may be related to administration frequency. Lack of persistence and adherence has potential clinical and economic consequences.

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

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. 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.

Effect of glipizide GITS on insulin sensitivity, glycemic indices, and abdominal fat composition in NIDDM

Glipizide in a once daily formulation utilizing the gastrointestinal therapeutic system (GITS) has been shown in preliminary studies to improve insulin sensitivity as assessed with meal tolerance testing. To evaluate the ability of glipizide GITS to specifically improve clinical insulin sensitivity in vivo, a double–blind, placebo-controlled trial randomized 40 NIDDM subjects to either glipizide GITS or placebo. The study was designed to evaluate NIDDM subjects whose fasting blood glucose was <190 mg% and Ghb <11% to avoid the adverse effects of hyperglycemia on insulin resistance and secretion. After screening, oral hypoglycemic agents were discontinued for one month, at which time a meal tolerance test with glucose and insulin response, glycated hemoglobin, and fructosamine were obtained. Insulin sensitivity (SI) and glucose effectiveness (Sg) were determined with a 4–h frequently sampled intravenous tolerance test (modified minimal model – 3rd phase insulin infusion) at baseline. Specific abdominal fat depots were quantitated by MRI scans. Patients were then randomized to receive placebo or active drug and all parameters were repeated at 1, 2, 5, and 8 months after randomization. Glipizide GITS significantly improved meal tolerance, reduced glycated blood proteins, and increased insulin sensitivity (P < .001). No change was seen for SG. There was no significant change in abdominal fat distribution during the trial. Glipizide GITS is effective in lowering glucose tolerance and improving insulin sensitivity without an increase in fasting insulin, weight gain, or change in abdominal fat composition. Drug Dev. Res. 44:1–7, 1998. © 1998 Wiley-Liss, Inc.