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PubMed2003

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↗

PubMed2001

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↗

PubMed2006

Economic impact of antidiabetic medications and glycemic control on managed care organizations: a review of the literature.

OBJECTIVE: To review the recent literature (January 2000-November 2005) regarding the impact of antidiabetic medications and glycemic control on the overall costs of care for patients with diabetes in U.S. managed care organizations (MCOs). SUMMARY: The pharmacy component accounts for typically 20% to 30% (full range, 10%-65%) of overall costs for MCO patients with diabetes. About 30% of pharmacy expenses are directly related to glycemic control, while the balance is spent on the management of macrovascular and microvascular complications related to diabetes and other common comorbidities such as hypertension and hyperlipidemia. Cost offsets and/or cost savings have been shown with the initiation of insulin therapy, including the use of newer short-acting insulins. Increasing medication possession ratios for antidiabetic medications (including insulins) are correlated with reduced overall health care costs, particularly reductions in hospitalization rates. Patients with diagnosed diabetes not receiving medications have significantly increased health care resource utilization. We identified 8 studies that indicatred that improvements in glycemic control lower overall per-patient direct costs within MCOs. CONCLUSIONS: The literature to date suggests that improving glycemic control and antidiabetic medication persistence reduce overall medical costs for patients with diabetes in managed care plans. Continued expansion of antidiabetic medication options will place increasing pressure on MCOs to assess the return on investment for newer pharmacotherapies. Routine measurement of economic and quality-of-life outcomes alongside clinical outcomes will become necessary for assessing the total value that new antidiabetic medications provide and whether cost offsets to managed care exist. Appropriate use of antidiabetic medications, including medication compliance, is an important component in a strategy to achieve glycemic control and may improve outcomes for patients with diabetes.

Blood Glucose↗

PubMed2001

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↗

PubMed2004

[Compliance and optimisation of oral antidiabetic therapy. A longitudinal study].

OBJECTIVE: To evaluate the impact of optimization of treatment and improvement in observance awareness in patients with type 2 diabetes on compliance with oral antidiabetic drug therapy and long-term glycemic control. Method Evaluation of compliance with oral antidiabetic therapy and of HbA1c levels in a cohort of 4 802 patients with type 2 diabetes followed by their general practitioner, before and after 6 Months on optimized treatment: reduction in percentage of combination treatments from 69.5 to 56.8%, and increase in percentage of once-daily dosing regimen from 12 to 58.4%. RESULTS: Optimization of treatment led to an increase in the percentage of patients achieving optimal compliance with oral antidiabetic drug therapy from 44 to 69.5% after 6 Months (p<0.001). Metabolic control also improved, as evidenced by a decrease in HbA1c levels observed both in the whole cohort (7.5+/-1.6% to 6.9+/-1.2%; p<0.0005), as well as in individual therapeutic subgroups of patients (having switched from multiple-daily dosing to once-daily-dosing schedules and from gliclazide 80 to gliclazide 30 MR once-daily formulation). CONCLUSION: These findings suggest that optimization of oral antidiabetic therapy favoring the use of oral antidiabetic agents with once-daily dosing administration modalities may improve metabolic control in patients with type 2 diabetes.

Administration, Oral↗

PubMed2003

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↗

PubMed2002

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↗

PubMed1993

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↗

PubMed2006

Managing psychiatric disorders with antidiabetic agents: translational research and treatment opportunities.

The objective of this paper is to synthesise extant studies describing the neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders. The authors conducted a MedLine search of all English-language articles published between 1966 and March 2006. The search terms were the nonproprietary names of established and putative antidiabetic agents (e.g., insulin, insulin secretagogues and sensitisers) cross-referenced with the individual names of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined mood, psychotic, anxiety and dementing disorders. The search was augmented with a manual review of article reference lists. Contemporary models of disease pathophysiology in major depressive disorder, bipolar disorder and several dementing disorders (e.g., Alzheimer's disease) emphasise alterations in cellular plasticity and cytoarchitecture, with associated regional abnormalities in neuronal and glial density and morphology. Antidiabetic treatments (e.g., thiazolidinediones) may be capable of attenuating this pathological process via disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory). Enhanced insulin signalling with antidiabetic treatments may preserve and/or augment cognitive function in several neuropsychiatric disorders. Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders.

Adult↗

PubMed1999

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↗

PubMed2026

Domesticated Argania spinosa in Eastern Morocco: HPLC-DAD/GC-MS Chemical Profiling, Antioxidant and Antidiabetic Activities, and Network Pharmacology-Guided Molecular Docking.

The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC50 values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843-0.967) and favorable binding affinities toward iNOS (ΔG = -9.3 kcal mol-1) and α-glucosidase (ΔG = -8.2 kcal mol-1). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59-0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE-RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation.

Sapotaceae↗

PubMed1994

Antiobesity and antidiabetic beta-agonists: lessons learned and questions to be answered.

In several species of obese animals, a group of phenethanolamine beta-agonists stimulates lipolysis and thermogenesis, resulting in the loss of body fat and weight. Brown adipose tissue is considered to be the major target tissue for the antiobesity activity of these compounds. Independent of this antiobesity activity, some of these compounds are also antidiabetic and increase muscle mass. Based on the pharmacological profile of these compounds, a beta3-receptor was proposed and characterized in mouse, rat, and humans. The beta3-receptor in brown adipose tissue has been suggested to mediate the antiobesity activity of these beta-agonists. Whether this receptor is responsible for the antidiabetic activity and whether there is a linkage between the antiobesity/antidiabetic activity and the nutrient partitioning activity is not clear. Clinical trials with these mixed beta-agonists showed marginal antiobesity effects when caloric intake of subjects was restricted. Insulin sensitivity was also improved in some of the trials designed to test the antidiabetic activity of these compounds. Side effects included tachycardia and tremor. To eliminate these side effects, a second generation of compounds was selected for its agonist activity on rat beta3-receptors. Clinical trials with these compounds have shown little increase of energy expenditure even at high doses. Successful development of an antiobesity and antidiabetic drug from this class of compounds will require the elucidation of the physiological role of the human beta3-receptor and the regulatory mechanism between fuel efficiency and feeding behavior.

Adrenergic beta-Agonists↗

PubMed2005

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats.

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.

Animals↗

PubMed2002

Adherence to oral antidiabetic therapy in a managed care organization: a comparison of monotherapy, combination therapy, and fixed-dose combination therapy.

BACKGROUND: Although medication adherence is one of the most important aspects of the management of diabetes mellitus, low rates of adherence have been documented. OBJECTIVE: This study sought to examine medication adherence among patients with diabetes mellitus in a managed care organization who were receiving antidiabetic monotherapy (metformin or glyburide), combination therapy (metformin and glyburide), or fixed-dose combination therapy (glyburide/metformin). METHODS: Medication adherence was evaluated through a retrospective database analysis of pharmacy claims. The adherence rate was defined as the sum of the days' supply of oral antidiabetic medication obtained by the patient during the follow-up period divided by the total number of days in the designated follow-up period (180 days). Health plan members were included in the analysis if they had an index pharmacy claim for an oral antidiabetic medication between August 1 and December 31, 2000, were continuously enrolled in the health plan, and were aged > or =18 years. A 6-month pre-index period was used to classify patients as newly treated or previously treated. Patients were grouped according to their medication-use patterns. RESULTS: After adjustment for potential confounding factors, including overall medication burden at index, there were no significant differences in adherence rates among 6502 newly treated patients receiving monotherapy, combination therapy, or fixed-dose combination therapy. Among the 1815 previously treated patients receiving glyburide or metformin monotherapy who required the addition of the alternative agent, resulting in combination therapy, adherence rates were significantly lower (54.0%; 95% CI, 0.52-0.55) than in the 105 patients receiving monotherapy who were switched to fixed-dose combination therapy (77.0%; 95% CI, 0.72-0.82). The 59 previously treated patients receiving combination therapy who were switched to fixed-dose combination therapy had a significant improvement in adherence after the switch (71.0% vs 87.0%; P < 0.001). CONCLUSIONS: In a managed care organization, previously treated patients receiving monotherapy with an oral antidiabetic medication who required additional therapy exhibited significantly greater adherence when they were switched to fixed-dose combination therapy compared with combination therapy. Patients receiving combination therapy who were switched to fixed-dose combination therapy exhibited significantly greater adherence after the switch.

Administration, Oral↗

PubMed2003

Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study.

PURPOSE: The current study was designed to evaluate the utility of antidiabetic medications in affecting changes in physical and cognitive functioning among older Mexican Americans with diabetes over a 2-year period. METHODS: A longitudinal analysis with repeated measurements between 1999 and 2001 was performed in a cohort of Mexican Americans, 60 or older, in the SALSA Project. Statistical analysis was conducted using a generalized estimating equation. RESULTS: For subjects with diagnosed diabetes </= 5 years (N = 381), there was less decline in physical and cognitive functioning over 2 years among subjects on treatment, compared to those without treatment. For subjects with diagnosed diabetes of 5+ years (N = 337), the effect of antidiabetic medications was more significant in preventing the decline in physical and cognitive functioning (ADL: mean in log scale = -0.10, 95% CI = -0.16, -0.04, 3MS: mean = 6.35, 95% CI = 3.23, 9.48). Combination therapy of antidiabetic agents appeared to be more effective than monotherapy in preventing the decline in physical and cognitive functioning for subjects. CONCLUSIONS: Antidiabetic drugs appear to be useful in alleviating the decline in physical and cognitive functioning among older Mexican Americans with diabetes, especially for those with a longer duration of the disease.

Activities of Daily Living↗

PubMed2002

Novel 5-substituted 2,4-thiazolidinedione and 2,4-oxazolidinedione derivatives as insulin sensitizers with antidiabetic activities.

Two novel classes of 2,4-thiazolidinediones and 2,4-oxazolidinediones with an omega-(azolylalkoxyphenyl)alkyl substituent at the 5-position were prepared and their antidiabetic effects were evaluated in two genetically obese and diabetic animal models, KKA(y) mice and Wistar fatty rats. A large number of the 2,4-thia(oxa)zolidinediones showed potent glucose- and lipid-lowering activities. The antidiabetic activities of the 2,4-oxazolidinediones were superior to those of the 2,4-thiazolidinediones. Among the compounds, both enantiomers of 5-[3-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxyphenyl]propyl]-2,4-oxazolidinedione (64), one of the most interesting compounds in terms of activity, were synthesized by using an asymmetric O-acetylation of the corresponding alpha-hydroxyvalerate (26) with immobilized lipase, followed by cyclization of the oxazolidinedione ring. (R)-(+)-64 showed more potent glucose-lowering activity (effective dose (ED)25 = 0.561 mg/kg/d) than (S)-(-)-64 (ED25 > 1.5 mg/kg/d) or pioglitazone (ED25 = 6 mg/kg/d) in KKA(y) mice. It also exhibited a 10-fold more potent antidiabetic activity (ED25 = 0.05 mg/kg/d) than pioglitazone (ED25 = 0.5 mg/kg/d) in Wistar fatty rats. The antidiabetic effects of this compound are considered to be due to its potent agonistic activity for peroxisome proliferator-activated receptor gamma (EC(50) = 8.87 nM).

Animals↗

PubMed2003

Insulin and longevity: antidiabetic biguanides as geroprotectors.

The results of previous experimental studies of effects of antidiabetic biguanides (phenformin and buformin) on life span and spontaneous tumor incidence in mice and rats were recalculated and reanalyzed using standard demographic models of mortality. The chronic treatment of female C3H/Sn mice with phenformin prolonged the mean life span by 21.1% (P < 0.05), the mean life span of the last 10% survivors by 28.4% and the maximum life span by 5.5 months (by 26%) in comparison with the control. The demographic aging rate represented by the estimate of respective Gompertz's parameter decreased by 31.2% and MRDT increased 1.45-fold. The treatment significantly inhibited (4.0-fold, P < 0.01) the incidence of mammary adenocarcinomas in mice. Administration of phenformin to female LIO rats failed to influence the mean life span. At the same time, the mean life span of the last 10% survivors increased by 10.1% (P < 0.05), and maximum life span increased by 3 months (+9.8%). Phenformin attenuated the development of spontaneous tumors in comparison to the control. The treatment of female rats with another antidiabetic biguanide, buformin, slightly increased their mean life span (by 7.3%; P > 0.05). The mean life span of the last 10% survivors increased by 12% (P < 0.05) and the maximum life span increased by 2 months (+5.5%) as compared with controls. The population aging rate decreased by 18.1% (P < 0.05) and MRDT increased 1.22-fold under the influence of buformin (P < 0.05). The total tumor incidence decreased by 49.5% in buformin-treated rats. Both antidiabetic biguanides slightly decreased the body weight, slowed down the age-related decline of the reproductive function in female rats. The results of our experiments provide evidence that antidiabetic biguanides are promising geroprotectors as well as drugs which can be used in the prevention of cancer.

Aging↗

PubMed1998

Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs.

OBJECTIVES: To examine the prescribing patterns, particularly antihypertensive and antidiabetic drugs, in a hospital outpatient clinic and to evaluate the expenditure incurred. METHODS: Prescriptions from a general medical outpatient clinic in a teaching hospital were collected for 4 weeks. Drug expenditures were calculated. RESULTS: A total of 622 prescriptions containing 1903 items were collected. Antihypertensive and antidiabetic drugs accounted for 25.9 and 9.1% usage, respectively. Calcium channel blocking agents, angiotensin converting enzyme inhibitors and beta-blocking agents were the most popular antihypertensive drugs used. Sulphonylureas were the most frequently prescribed antidiabetic agents. Amlodipine, doxazosin and sotalol accounted for 4.5% of all prescription items but 27.8% of the total drug expenditure. CONCLUSION: The use of antihypertensive and antidiabetic drugs accounted for most of the drug usage in this study. Use of newer and more expensive agents has further increased drug expenditure. Monitoring drug usage and their correlations with clinical outcomes are warranted.

Aged↗