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At least 19 recordsLinked to original sources

Utilization of antidiabetic drugs in Hong Kong: relation to the common occurrence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions and the relative prevalence of NIDDM.

Antidiabetic drug-induced hypoglycemia as a cause of acute medical admissions is more common in Hong Kong (1.7%) than in other countries (0.1-0.5%). To determine if this higher incidence may be related to the frequent use of some sulphonylureas, we have studied the overall prescribing patterns in the public sector in 1994 by reviewing the utilization of antidiabetic drugs in the general out-patient/general practice clinics (GOPD) and Hospital Authority public hospitals and affiliated specialist clinics (HA). The vast majority of patients (90.5%) receiving antidiabetic treatment were taking sulphonylureas and/or metformin, confirming that diabetes mellitus in Hong Kong is predominantly of the noninsulin-dependent type. The GOPD and the HA each accounted for approximately half of the sulphonylureas (55% vs 45%) and metformin (43% vs 57%) prescribed. Glibenclamide (84.9% vs 79.1%, 83.7% overall) and gliclazide (12.8% vs 16.6%, 14.5% overall) were the 2 most frequently used sulphonylureas. Only 9.5% of patients on antidiabetic drugs were receiving insulin and 92% of this was prescribed by the HA. For comparison, Singapore has a similar prevalence of diabetes mellitus but a much lower incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions (0.5%). Tolbutamide was the most frequently used there sulphonylurea (66.6-72.2%) with glibenclamide only contributing 20.8-28.6%. Thus, the predominant use of glibenclamide in Hong Kong may contribute to the high incidence of antidiabetic drug-induced hypoglycemia amongst acute medical admissions.

Acute Disease↗

[New oral antidiabetic agents and current strategies of peroral antidiabetic therapy (PAD)].

Optimal compensation in patients with type 2 diabetes is individualization of therapy according to the stage of the disease and ratio of the main pathophysiological disorders. Because of the hitherto inadequate effectiveness of known procedures attention is focused on seeking new more effective procedures either based on the use of known molecules of oral antidiabetics or introduction of new substances.

Administration, Oral↗

An investigation into antidiabetic medication prescribing in South Africa.

BACKGROUND: The number of people with diabetes in Africa is expected to triple in the next 15 years, which will have a significant impact on the prescribing and use of antidiabetic medication. OBJECTIVE: The primary aim of this study was to investigate the prescribing patterns of antidiabetic medication that are used on a chronic basis in South Africa. METHOD: Prescribing data of 1100 diabetic patients were retrospectively analysed over a 1-year period. RESULTS: The average age of patients was 53.2 years (SD = 16.4 years), with more male than female patients. The oral antidiabetic drugs accounted for 67.4% of all the antidiabetic products prescribed, with the sulphonylureas the most frequently prescribed antidiabetic therapeutic subgroup. Glicazide was the single most frequently prescribed oral antidiabetic drug, accounting for 38.2% of all oral agents. Biphasic insulin was the most frequently prescribed class of insulin. Fifty-seven patients were using insulin as well as one or more oral antidiabetic drugs. Cardiovascular system drugs, nervous system drugs and drugs acting on the alimentary tract and metabolism together accounted for more than half of the drugs that were prescribed concurrently with antidiabetic medication. CONCLUSION: Further research on the prescribing of antidiabetic medication should be conducted focusing on the qualitative aspects of treatment and treatment costs as well as studies on antidiabetic treatment in the public health sector.

Adult↗

Rapid increase in the use of oral antidiabetic drugs in the United States, 1990-2001.

OBJECTIVE: To describe the use of oral antidiabetic drugs for management of type 2 diabetes in the U.S. from 1990 through 2001. RESEARCH DESIGN AND METHODS: Data on oral antidiabetic drugs were derived from two pharmaceutical marketing databases from IMS Health, the National Prescription Audit Plus and the National Disease and Therapeutic Index. RESULTS: In 1990, 23.4 million outpatient prescriptions of oral antidiabetic agents were dispensed. By 2001, this number had increased 3.9-fold, to 91.8 million prescriptions. Glipizide and glyburide, two sulfonylurea medications, accounted for approximately 77% of prescriptions of oral antidiabetic drugs in 1990 and 35.5% of prescriptions in 2001. By 2001, the biguanide metformin (approved in 1995) had captured approximately 33% of prescriptions, and the thiazolidinedione insulin sensitizers (rosiglitazone and pioglitazone marketed beginning in 1999) accounted for approximately 17% of market share. Compared with patients treated in 1990, those in 2001 were proportionately younger and they more often used oral antidiabetic drugs and insulin in combination. Internists and general and family practitioners were the primary prescribers of this class of drugs. CONCLUSIONS: Consistent with the reported increase in the prevalence of type 2 diabetes, the number of dispensed outpatient prescriptions of oral antidiabetic drugs increased rapidly between 1990 and 2001. This period was marked by an increase in the treatment of younger people and the use of oral antidiabetic drugs in combination. With the approval in the last decade of several new types of oral antidiabetic medications with different mechanisms of action, options for management of type 2 diabetes have expanded.

Administration, Oral↗

Differences in antidiabetic drug utilisation between three different health systems in the same national region.

The consumption of antidiabetic drugs in a Spanish region (Extremadura) in the period 1986-1987 has been investigated by the "defined daily dose" (DDD) method. The study was done in three health care systems in the region: civil servants ("Mutualidad de Funcionarios Civiles del Estado: MUFACE") armed forces group ("Instituto Social de las Fuerzas Armadas: ISFAS") and the national system ("Instituto Nacional de la Salud: INSALUD"). The total consumption of antidiabetic drugs varied three-fold, ranging from 5,73 DDD per 1000 inhabitants per day (3,71 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 2,02 DDD per 1000 inhabitants per day for insulin) in the civil servant group to 15,82 DDD per 1000 inhabitants per day (12 DDD per 1000 inhabitants per day for oral antidiabetic drugs and 3,82 DDD per 1000 inhabitants per day for insulins) in the armed forces. The differences were more pronounced for oral antidiabetics than for insulins. The utilization of insulin among the civil servants was about half of that by the two other groups. Of oral antidiabetics, sulphonylureas were the most frequently used by the three groups, and within them glibenclamide accounted for more than half of the DDDs, while biguanides were scarcely used in any group. The differences are difficult to assess, since they could be due to several factors, such as age-differences in the population studied, different prescribing habits, and differences in sociocultural level. The results justify further comparative studies of drug utilization in different health systems within the same region.

Drug Utilization↗

The development of an oral antidiabetic combination tablet: design, evaluation and clinical benefits for patients with type 2 diabetes.

Type 2 diabetes is a chronic and progressive disease. Oral antidiabetic monotherapies directly address only one defect as their primary mechanism of action, and do not control blood glucose sufficiently well to meet current glycaemic targets. In consequence, most patients need combination therapy within a few years. However, the co-administration of two or more oral antidiabetic drugs may render treatment regimens difficult to follow. Combining oral antidiabetic agents into a single tablet provides a means of intensifying antidiabetic therapy while supporting good patient compliance. An insulin sensitiser and an insulin secretagogue represent a rational oral antidiabetic combination, as they address the dual endocrine defects of insulin resistance and impaired beta-cell function in type 2 diabetes. Nevertheless, the components of a combination tablet must be carefully chosen. Metformin (an insulin sensitiser) and glibenclamide (an insulin secretagogue) are well supported by decades of clinical evidence, and the pharmacokinetics of these agents support twice-daily co-administration. The final technical challenge is to optimise their delivery within a single-tablet combination. A recently-introduced metformin-glibenclamide combination tablet (Glucovance) has been extensively studied in well-designed clinical trials, where it has been shown to be more effective than its component monotherapies in controlling fasting and postprandial glycaemia. This treatment provides a case study in the development of a single-tablet oral antidiabetic combination, in terms of the pharmacokinetic issues facing the development of this preparation, and the implications of the pharmacokinetic properties of the components of the combination tablet on their pharmacodynamic actions and risk-benefit profile.

Administration, Oral↗

Isolation of antidiabetic components from white-skinned sweet potato (Ipomoea batatas L.).

We have already reported that white-skinned sweet potato (Ipomoea batatas L.) (WSSP) shows antidiabetic activity in streptozotocin (STZ) induced diabetic rats and genetically diabetic models (yellow KK, db/db mice and Zucker fatty rats). In this study, isolation and purification of the antidiabetic component of WSSP were attempted. Almost all antidiabetic activity was found in the cortex of WSSP. The fractionation of the antidiabetic component in the WSSP cortex was done by the following methods: dialysis of the water extract, 85% ethanol precipitation, 15% trichloroacetic acid (TCA) treatment, butyl-, phenyl-hydrophobic column chromatography, and ultrafiltration treatment. The antidiabetic component was not eliminated during dialysis and was soluble in 85% ethanol and 15% TCA, but it passed through a filter that allows the passage of substances of a molescular weight of 30,000. The uniformity of this isolated active component was analyzed using HPLC. A single peak was seen with three different columns (C8 reverse-phase column, anion exchange QA column, and gel filtration column (GFC)), indicating that the component is a uniform substance. The molecular weight of this antidiabetic component was estimated to be 22,000 by GFC analysis. This active component was presumed to be an acidic glycoprotein because it contained protein and sugar and was adsorbed onto the QA column at pH 7.0.

Animals↗

Oral antidiabetic drugs: preoperative stop or continue?

In recent years, a lot of concern about the use of oral antidiabetics has been raised. Several studies indicate an excess cardiovascular morbidity and mortality associated with the use of oral antidiabetics in the treatment of non-insulin dependent diabetes mellitus. Only recently, the identification of the KATP-channels and it's pivotal role in the phenomenon of ischemic preconditioning has lead to a clear explanation of these disturbing findings. The antagonism of KATP-channels by the sulphonylurea-class type of oral antidiabetics interferes with ischemic preconditioning. The question has been raised what to do with oral antidiabetics during the perioperative setting with it's additional burden imposed on the cardiovascular system. In this article the historical background, the phenomenon of ischemic preconditioning, the importance of KATP-channels and the working mechanism of the oral antidiabetics are highlighted. A few thoughts on the use of oral antidiabetics in the perioperative setting are developed and clinical conclusions drawn.

Administration, Oral↗

Influence of oral antidiabetic drugs compliance on metabolic control in type 2 diabetes. A survey in general practice.

BACKGROUND: To address compliance with oral antidiabetic agents and its impact on metabolic control in type 2 diabetic patients treated in general practice. METHODS: Prospective assessment of self-reported compliance with a standardized questionnaire in an homogeneous cohort of 11,896 type 2 diabetic patients treated by their general practitioner with one or two oral antidiabetic agents, and analysis of determinants of compliance with treatment (age, diabetes duration, educational level, severity of complications, frequency of antidiabetic oral agents daily dosing). RESULTS: Optimal compliance (no omission) was reported in only 46% of cases. In multivariate analysis, HbA(1c) levels were positively correlated with age, daily dosing frequency of oral antidiabetic agents and low educational level, but not with diabetes duration. Low daily dosing was associated with a better metabolic control. HbA(1c) levels were associated with compliance with treatment, with a 1.4% mean difference between group with optimal and group with worst compliance. CONCLUSIONS: These results suggest the interest of reducing daily dosing frequency of oral antidiabetic agents, in order to improve compliance with treatment and metabolic control.

Administration, Oral↗

Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay).

BACKGROUND: Potential phototoxicity has been described for a number of drugs and chemical substances. Psoralens, chlorpromazines and fluoroquinolones have been described as inducing photomutagenicity and photocarcinogenicity in vitro and in vivo. We wanted to investigate oral antidiabetics and diuretics for potential phototoxicity and possible DNA damage in the HaCaT cell line. METHODS: : The oral antidiabetics tolbutamide, glibenclamide and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide and trichlormethiazide were dissolved in DMSO to final concentrations of 1 mM, 0.1 mM, and 0.01 mM, incubated together with the cells, and exposed to UVA1 (23 or 48 J/cm2). Cell survival was evaluated in a clonogenic assay and phototoxic DNA damage was investigated by single cell gel electrophoresis (comet assay). To investigate possible inhibiting effects of antioxidants, L-ascorbic acid and alpha-tocopherol were added at a final concentration of 1 mM 24 h before treatment with the drugs. RESULTS: Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide and tolbutamide induced dose-dependent phototoxicity in the clonogenic assay. Cells incubated with bendroflumethiazide, tolbutamide and glibenclamide and irradiated with UVA1 demonstrated increased oxidative DNA damage, revealed as alkali-labile sites in the comet assay. Pretreatment with L-ascorbic acid or alpha-tocopherol suppressed the UVA-induced DNA damage in cells incubated with 1 mM bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide or trichloromethiazide. CONCLUSION: Several oral antidiabetics and diuretics show phototoxic effects in the HaCaT cell line. Inhibiting effects of antioxidants point towards involvement of reactive oxygen species in phototoxic DNA damage, suggesting a link between the phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs. Excessive exposure to UV light may be deleterious for patients treated with oral antidiabetic and diuretic drugs.

Cell Death↗

ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release.

The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by antidiabetic sulfonylureas. Diazoxide opens ATP-sensitive K+ channels in adenohypophysis cells as it does in pancreatic beta cells and also induces a hyperpolarization (approximately 30 mV) that is also suppressed by antidiabetic sulfonylureas. As in pancreatic beta cells, glucose and antidiabetic sulfonylureas depolarize the adenohypophysis cells and thereby indirectly increase Ca2+ influx through L-type Ca2+ channels. The K+ channel opener diazoxide has an opposite effect. Opening ATP-sensitive K+ channels inhibits growth hormone secretion and this inhibition is eliminated by antidiabetic sulfonylureas.

Adenosine Diphosphate↗

Frequency of liver disease in type 2 diabetic patients treated with oral antidiabetic agents.

OBJECTIVE: We evaluated liver disease in conventionally treated type 2 diabetic patients to provide a reference against which reports of liver disease related to novel oral antidiabetic treatments could be compared. RESEARCH DESIGN AND METHODS: In this follow-up study, patients with type 2 diabetes who were treated with oral antidiabetic agents were identified from the U.K.-based General Practice Research Database and were followed to determine whether they developed liver disease. The specific types and etiologies of liver disorders were determined. Incidence rates were calculated based on the accumulated exposure time to oral antidiabetic agents. RESULTS: Among 44,406 type 2 diabetic patients, 605 had a computer diagnosis of liver disease with an incidence rate of 53.2/10,000 person-years (95% CI 49.2-57.6). Of the 605 subjects, 186 had nonsymptomatic, mild, and transient liver disorders; 249 had a predisposing condition; and 113 had another cause for the disease. A total of 57 cases were possibly drug induced with an incidence rate of 5.0/10,000 person-years (3.9-6.5). Of the cases, 11 were attributed to other drugs, 8 were attributed to fatty liver disease of diabetes, and the remaining cases were attributed to uncertain causes. Oral antidiabetic agents were continued in 51 of these 57 cases, and we could not rule out oral antidiabetic agents as a cause of liver disease in 2 cases with an incidence rate of 0.2/10,000 person-years (< 0.1-0.6). CONCLUSIONS: In this population, the background incidence of liver disease was high. Most cases involved other systemic diseases that may cause liver disease.

Administration, Oral↗