Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTIDIABETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1998

A short term cost-effectiveness model for oral antidiabetic medicines in Europe.

A short term (6-month) cost-effectiveness model has been developed to simulate current medical practice and disease progression in patients with type 2 (non-insulin-dependent) diabetes mellitus uncontrolled by diet and exercise. The model is based on decision-analytical techniques and includes probabilities of switching between treatments, the reason for the switch and the most common switch options. Effectiveness and economic measures are the 2 main outcomes. In order to assess effectiveness, we use symptom-free days with acceptable control (SFDACs), which represent each day of treatment without adverse events or symptoms, and with acceptable control of glucose and lipids. For the economic evaluation, only incremental costs incurred directly by a health insurance system are considered. This model should prove useful in the evaluation of new oral antidiabetic agents, since the short term aim of antidiabetic therapy is to provide adequate control in the absence of adverse effects and symptoms (a prerequisite for successful long term treatment). Furthermore, short term analysis provides data for comparing initial investment in drug therapy with potential savings over a longer treatment period.

Cost-Benefit Analysis↗
PubMed2004

Structurally modified analogues of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) as future antidiabetic agents.

Glucagon-like peptide-1(7-36)amide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal insulin-releasing hormones involved in the regulation of postprandial nutrient homeostasis. These two incretin hormones are glucose-dependent stimulators of pancreatic beta-cell function, exhibiting a spectrum of secondary extrapancreatic activities, which favour the efficient control of blood glucose homeostasis. Such actions of GLP-1 and GIP have generated considerable interest in their possible exploitation as novel agents for the treatment of type 2 diabetes. Despite the many attributes of GLP-1 and GIP as possible future antidiabetic agents, their rapid degradation in the circulation by dipeptidyl peptidase IV (DPP IV) to inactive truncated forms GLP-1(9-36)amide and GIP(3-42), severely limits their therapeutic usefulness. This review will consider recent developments in the design and effectiveness of synthetic DPP IV-resistant analogues of GLP-1 and GIP. Consideration will be given to the effects of N-terminal modification and amino acid substitution of GLP-1 and GIP either side of the DPP IV cleavage site on (i) susceptibility to enzymatic degradation, (ii) binding to native hormone receptor, (iii) ability to elevate intracellular cyclic AMP, (iv) potency as insulin secretagogues, and (v) antihyperglycaemic activity in type 2 diabetes. It will be shown that structural modification can produce a varied set of biological activities, ranging from more efficacious analogues to those which antagonise the activity of the native hormone. The antidiabetic properties of the best GLP-1 and GIP analogues indeed promise to provide the basis for novel, effective and long-acting drugs for type 2 diabetes therapy. This approach is currently being pursued actively by the pharmaceutical industry.

Animals↗
PubMed1977

The effect of chronic oral antidiabetic therapy on insulin and glucagon responses to a meal.

Nineteen maturity-onset diabetic patients receiving oral hypoglycemic therapy in a university diabetes clinic completed a study to assess the efficacy of the oral agents and to determine their effects on pancreatic islet hormone secretion. All patients were receiving sulfonylureas, and seven were also receiving phenformin. The subjects were studied as outpatients in the clinic setting on four different occasions with collections of a baseline blood sample before a standard breakfast and a second sampling two hours postprandially, twice while on their prescribed medication and twice after having been withdrawn from the medication. The values obtained during the two studies on the two studies off medications were reproducible for each subject. Analysis of the results by paired differences revealed that mean 24-hour urine glucose values deteriorated significantly (p less than 0.005) after oral antidiabetic therapy was withdrawn; similarly, mean plasma glucose values, both at baseline and two hours postprandially, rose significantly (p less than 0.001) when subjects were off medication. Baseline serum insulin values were not changed, but postprandial levels were significantly higher on oral agents (p less than 0.005). Plasma immunoreactive glucagon was significantly lower both at baseline (p less than 0.02) and postprandially (p less than 0.005) when the subjects were on their antidiabetic medications. During the trial off medication, 16 patients became symptomatic, with three of these developing symptoms severe enough to require hospitalization. It is apparent from this study that oral hypoglycemic medications can play a role in controlling symptoms in maturity-onset diabetic patients and that the beneficial effect of these agents on hyperglycemia may, in part, be explained by their stimulation of endogenous insulin secretion and partial suppression of endogenous glucagon.

Acetohexamide↗
PubMed1988

Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats.

CS-045 is a new oral antidiabetic agent that was effective in insulin-resistant diabetic animal models, including the KK mouse, the ob/ob mouse, and the Zucker fatty rat. CS-045 was not effective in the streptozocin-treated mouse, an insulin-deficient diabetic animal model. In fed KK mice, CS-045 lowered the plasma glucose levels in a dose-dependent manner after a single oral administration, and the hypoglycemic effect lasted for at least 18 h. In normal rats, however, plasma glucose levels were not changed after administration of CS-045. CS-045 when given chronically (2 wk) to diabetic KK and ob/ob mice as a 0.2% food admixture dramatically improved hyperglycemia, hyperinsulinemia, and hypertriglyceridemia to near-normal values and decreased plasma lactate, free fatty acid, and ketone body levels without reducing food intake or body weight. In the obese Zucker fatty rat, oral administration of CS-045 had a similar effect in lowering plasma glucose, insulin, triglyceride, free fatty acid, lactate, and ketone body levels. The CS-045-treated Zucker fatty rats showed increased glucose tolerance and decreased insulin secretion in response to oral glucose. After 9 days of treatment, insulin binding to adipocyte plasma membranes from both CS-045-treated Zucker fatty rats and KK mice was increased. Furthermore, 2-deoxyglucose uptake in CS-045-treated adipocytes was increased and the insulin dose-response curve was shifted to the left. These findings suggest that CS-045 increases not only insulin sensitivity but also insulin responsiveness. Based on its pharmacological profile, CS-045 is a new orally effective antidiabetic agent that may reduce abnormalities of glucose and lipid metabolism in obese and non-insulin-dependent diabetes mellitus patients with insulin resistance.

Adipose Tissue↗
PubMed2003

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats.

In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations, we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition, incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors in antidiabetic therapy.

Adipocytes↗
PubMed2004

Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?

Metformin and thiazolidinediones (TZDs) are believed to exert their antidiabetic effects via different mechanisms. As evidence suggests that both impair cell respiration in vitro, this study compared their effects on mitochondrial functions. The activity of complex I of the respiratory chain, which is known to be affected by metformin, was measured in tissue homogenates that contained disrupted mitochondria. In homogenates of skeletal muscle, metformin and TZDs reduced the activity of complex I (30 mmol/l metformin, -15 +/- 2%; 100 micromol/l rosiglitazone, -54 +/- 7; and 100 micromol/l pioglitazone, -12 +/- 4; P < 0.05 each). Inhibition of complex I was confirmed by reduced state 3 respiration of isolated mitochondria consuming glutamate + malate as substrates for complex I (30 mmol/l metformin, -77 +/- 1%; 100 micromol/l rosiglitazone, -24 +/- 4; and 100 micromol/l pioglitazone, -18 +/- 5; P < 0.05 each), whereas respiration with succinate feeding into complex II was unaffected. In line with inhibition of complex I, 24-h exposure of isolated rat soleus muscle to metformin or TZDs reduced cell respiration and increased anaerobic glycolysis (glucose oxidation: 270 micromol/l metformin, -30 +/- 9%; 9 micromol/l rosiglitazone, -25 +/- 8; and 9 micromol/l pioglitazone, -45 +/- 3; lactate release: 270 micromol/l metformin, +84 +/- 12; 9 micromol/l rosiglitazone, +38 +/- 6; and 9 micromol/l pioglitazone, +64 +/- 11; P < 0.05 each). As both metformin and TZDs inhibit complex I activity and cell respiration in vitro, similar mitochondrial actions could contribute to their antidiabetic effects.

Animals↗
PubMed1991

Metabolic control in diabetic subjects in three Swedish areas with high, medium, and low sales of antidiabetic drugs.

OBJECTIVE: The relationship between use of antidiabetic drugs and metabolic control was studied in Swedish diabetic populations in areas with high (Gotland), medium (Tierp), and low (Skellefteå) sales of antidiabetic drugs. RESEARCH DESIGN AND METHODS: The study population consisted of 405 drug-treated diabetic subjects aged 50-74 yr. In all three areas, glyburide comprised approximately 75% of the oral treatment. RESULTS: In accordance with sales, Gotland was found to be a heavy-use area, characterized by a high prevalence of insulin treatment (43%), combination therapy with sulfonylureas and biguanide (28%), and high prescribed daily doses (PDDs) of glyburide (15.5 +/- 0.8 mg) compared with other areas. In Skellefteå, 38% were on insulin, 4% were on combination therapy, and the PDD of glyburide was 7.1 +/- 0.6 mg. In Tierp, 27% were on insulin, 26% were on combination therapy, and the PDD of glyburide was 11.4 +/- 0.7 mg. In Gotland, both men and women had significantly lower HbA1c levels, regardless of treatment mode, and a tendency to be more overweight compared with the area with the least pharmacological intensity (Skellefteå). CONCLUSIONS: In the three diabetic populations, good metabolic control, defined as an HbA1c level of less than 7% and acceptable weight control (body mass index less than 27 for men and less than 25 for women), was achieved among only 16% in Gotland, 17% in Skellefteå, and 12% in Tierp.

Administration, Oral↗
PubMedDate not supplied

Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes.

To study the etiopathogenesis of secondary drug failure to treatment with oral antidiabetic agents in patients with non-insulin-dependent diabetes (NIDD) we compared 60 "nonresponders" with 60 "responders" to treatment with oral drugs. Secondary drug failure was defined as mean diurnal blood glucose greater than 12 mmol/L after an initial good response of greater than or equal to 2 yr. The nonresponders were characterized by 50% lower C-peptide concentrations than the responders (P less than 0.001). We could not, however, define a critical C-peptide level to discriminate between patients requiring and not requiring insulin therapy. There was a wide overlap of individual C-peptide values between responders and nonresponders that attenuates the clinical value of single C-peptide measurements in predicting therapy. Only by serial measurements over a period of time was it possible to achieve information about changes in beta cell function. The nonresponders showed increased frequency of islet cell (P less than 0.01), thyroid antimicrosomal (P less than 0.01), and gastric parietal cell antibodies (P less than 0.02). In nonresponders, HLA-antigen B8 was increased (P less than 0.05) and HLA-B7 decreased (P less than 0.01) compared with frequencies of responders. In conclusion, impaired beta cell function is a characteristic feature of many, but not all, NIDD patients who fail on treatment with oral antidiabetic drugs. The presence of islet cell and thyrogastric antibodies can unmask a distinct group of NIDD patients with a high risk of secondary drug failure and subsequent insulin dependency. HLA typing may further help to predict secondary failure in NIDD.

Administration, Oral↗
PubMed1986

Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs.

We have previously shown that the antidiabetic property of fenugreek seeds (Trigonella foenum graecum L.) is associated with the defatted seed material which is rich in fibers, saponins, and proteins. In the present work this defatted preparation was divided into two subfractions: subfraction "a" which contains the testa and endosperm and is rich in fibers (79.6%); and subfraction "b" which contains the cotyledons and axes and is rich in saponins (7.2%) and proteins (52.8%). We investigated the effects of each subfraction on hyperglycemia and the levels of pancreatic hormones when chronically administered to alloxan-diabetic dogs. Each subfraction was studied separately and was given to the dogs per os (mixed with the two daily meals), in addition to the insulin treatment (which was kept the same throughout the experiment) for a period of 21 days. The addition of subfraction "a" to insulin treatment resulted in a clear decrease of hyperglycemia and glycosuria accompanied by a reduction of the high plasma glucagon and somatostatin levels in diabetic dogs. The treatment also decreased the hyperglycemic response to the oral glucose tolerance test. In contrast the chronic administration of subfraction "b" had no effect on hyperglycemia or on the levels of pancreatic hormones in diabetic dogs. Our results show that the antidiabetic properties of fenugreek seeds are contained in the testa and endosperm. Although this subfraction is rich in fibers (high viscosity; 115 cP), it is not possible to exclude the existence of one or more unknown active pharmacological compounds in this subfraction of the seed.

Animals↗
PubMedDate not supplied

Triple oral antidiabetic therapy in type 2 diabetes mellitus.

To determine the effectiveness of triple oral antidiabetic therapy with a sulfonylurea, a biguanide, and a thiazolidinedione, we analyzed the results in 35 patients who had previously had inadequate glycemic control with a combination of glimepiride and metformin. The study cohort consisted of 27 men and 8 women (mean age, 55.8 years) who had had type 2 diabetes mellitus for a mean duration of 8.7 years. The addition of troglitazone (600 mg/day administered with the largest meal) to the glimepiride and metformin therapy yielded normal or near-normal glycemia in all 35 patients. Glycemic control was initially associated with mean weight gain; subsequently, however, mean weight was reduced to below the baseline level--perhaps attributable to the anorectic effect of metformin. Thus, for the first time, triple oral antidiabetic therapy with glimepiride, metformin, and troglitazone has been shown to be an efficacious therapeutic option for type 2 diabetes.

Journal Article↗
PubMedDate not supplied

[Trends of antidiabetic drug prescriptions in Andalucia (1986-1994)].

OBJECTIVE: Tendencies in the consumption of antidiabetic agents in Andalusia between 1986-1994 were analysed, with special emphasis on the impact of the introduction of acarbose and mechanized systems for the injection of insulin. METHODS: The information concerning consumption was obtained from the data bases of the Andalusian Health Service and the Ministry of Health which contain details of the items sold in community chemists and charged to the National Health System. Data are expressed as defined daily doses per 1000 inhabitants per day (DID). RESULTS: Insulin consumption rose from 4.67 DID in 1986 to 9.33 DID en 1994, an increase (delta) of 99.8%. All types of insulins contributed to the increase, with the mixtures rising most (delta 275%). Intermediate insulins were the most used. Prefilled syringes accounted for 25% of all insulin dispensed in 1994. Consumption of oral antidiabetic agents (OAA) rose from 12.75 DID in 1986 to 20.92 DID in 1994 (delta 64%). The most prescribed OAAs during these years were second generation sulphonylureas, representing 83% of those dispensed in 1994, followed by acarbose (11%), biguanides (3.8%), and first generation sulphonylureas (2.1%). CONCLUSIONS: There was a notable increase in the consumption of insulins and OAAs. Although the tendency in the consumption differs from that expected according to consensus agreements, qualitative changes were seen, suggesting an improvement in prescription habits. The appearance of mechanized injection systems for insulin and of acarbose have clearly modified prescription habits.

Drug Prescriptions↗
PubMed2000

[Therapy of type 2 diabetes. Critical evaluation of oral antidiabetic drugs].

Changes in lifestyle and eating habits always form the initial phase of treatment of type 2 diabetes. Sooner or later, type 2 diabetes is associated with a lack of insulin that makes treatment with insulin necessary. Today, however, modern oral antidiabetics make it possible to exert a selective positive influence on both insulin resistance and disturbed insulin secretion. Three main groups of substances are available. Among the stimulators of insulin secretion are the sulfonylureas (e.g. glibenclamide, glibonuride, glisoxepid, glimepiride), and the so-called prandial glucose regulators, such as repaglinide, which differ from the sulfonylureas both chemically and in their pharmacodynamic properties. The group of insulin sensitizers includes the biguanide, metformin and the thiazolidinediones or glitazones (rosiglitazone, pioglitazone). The third group are the alpha-glucosidase inhibitors, e.g. acarbose. In principle, these oral antidiabetics can be combined with one another.

Blood Glucose↗
PubMed2000

[Pharmacoepidemiology of diabetes: assessment of good use of oral antidiabetic drugs].

Diabetes' treatment is specific; therefore diabetic patients can be identified by the prescription of antidiabetic drugs. This pathology is characterized by chronicity and occurrence of complications which need additional medications. All the drugs have official use guidelines due to drug interactions and/or physiological status of the patients. To evaluate how these guidelines are followed in general practice, we used a data base from the French Health care System. Two thousand eight hundred and ninety eight (2 898) prescriptions on which, at least, one oral antidiabetic drug was noticed, were analysed. The number of drugs on each prescription was between 1 and 18 (mean (5,6 +/- 2,9)). Considering the drugs which need precautions of use in association with sulfonylureas, coprescription occurred with B-bloquants and non steroid anti-inflammatory drugs in 18 and 17 % of the cases respectively. The drugs which need precautions of use in association with biguanides were diuretics, oestrogens and/or progestatives and steroids, coprescribed in 28, 1, 1 % of the cases respectively. Percentages of coprescriptions which need precautions of use were quite high. The relevance of detected coprescriptions. and the compatibility between recommendations for "good prescription" and "real prescription practice" should be taken into account considering diabetic patients' characteristics.

Administration, Oral↗
PubMedDate not supplied

[Effect of oral antidiabetic agents on fructose biosynthesis].

The oral antidiabetic drugs (glyformin, glyclaside, glycvidon, glybenclamide) at a concentration of 10-196 mM affect the synthesis of fructosamine in an incubation medium containing 40 mM of glucose and 5% of human serum albumin. All these drugs decrease the fructosamine yield measured in the medium on the 4th day of incubation at 37-198 degrees C, while the effect of glycvidon is pronounced even on the 7th day. The introduction of glyformin, glycvidon, and glybenclamide at an amount close to the maximum daily dose over a period of one month reduces the level of fructosamine in the blood of rats with experimental diabetes mellitus, while not affecting the level of glucose in the blood of test animals. Thus, the oral antidiabetic drugs reduce the level of fructosamine--an agent known to modify the protein structure, thus favoring the development of complications in the course of diabetes under permanent hyperglycemia conditions.

Administration, Oral↗
PubMed2000

[Clinically important effects of oral antidiabetic drug interactions].

Most of type 2. diabetic patients require medication for several concomitant diseases, most important being, hypertension, ischaemic heart disease, heart failure, dyslipidaemias, obesity. Thus the risk of drug interactions is important, particularly in elderly patients. Oral antidiabetic drugs include hypoglycaemic agents (sulphonylureas, meglitenides) and biguanides (metformin), alpha-glucosidase inhibitors, tiazolinidediones. Drug interactions with antihyperglycaemic agents can be divided into pharmacokinetic and pharmacodynamic interactions. Numerous drugs due to interactions enhance hypoglycaemic action of sulphonylureas, thus increase the risk of hypoglycaemia. Several drugs may cause impairment of glycaemic control through various mechanisms in diabetic patients treated with oral antidiabetic drugs. Currently the most controversial problem is safety of combination therapy with sulphonylurea and metformin, as several observations indicated that it can increase mortality from cardio-vascular causes.

Administration, Oral↗
PubMed2001

[Current and future aspects of oral antidiabetic agents in type 2 diabetes].

Type 2 diabetes mellitus is characterized by insulin deficiency but in particular by insulin resistance. Patients where it is not possible to achieve positive results within 4-12 weeks by optimalization of the lifestyle are candidates for treatment with oral antidiabetics. At present the following main groups of oral antidiabetics are discussed: insulin secretagogues (SU derivatives and methiglinide derivatives), biguanides (Metformin), alpha-glucosidase inhibitors (acarbose, miglitol) and insulin sensitizers (thiazolindiones). Traditional SU therapy improves the insulin plasma levels by releasing insulin from the pancreas. This implies further stress on the b-cells and the function of these cells declines reversibly. Biguanides, such as metformin, are effective substances reducing the blood sugar level, they are however associated with the problem of tolerability and are contraindicated in some diabetics. A new approach to the treatment of type 2 diabetes are thiasolinediones, insulin-sensitizing substances, the molecular basis of their action being via activation of PPAR gamma-nuclear receptors with subsequent change in expression of genes participating in carbohydrate and lipid metabolism.

Administration, Oral↗
PubMed2001

[Development of new antidiabetic drugs through the advanced knowledge of molecular biology in insulin signal transduction].

The advancement of molecular biology in the field of insulin signal transduction is remarkable and the knowledge acquired through the recent research can be applied to the development of new antidiabetic drugs. There are several serine-threonine kinases and tyrosine phosphatases which can decrease insulin action at the state of diabetes and adipocytokines, which are produced from enlarged adipocytes, may affect insulin signal transduction. To prevent these proteins and cytokines from suppressing insulin action, specific molecular targets could be identified and the new agents can be developed for the normal insulin signaling and the development of new antidiabetic drugs is ongoing at present time.

Adipocytes↗
PubMed2001

New antidiabetic medications. Clinical evidence, clinical practice and pharmacoeconomics.

BACKGROUND: Type 2 diabetes is a progressive and complex disease with underlying defects in insulin sensitivity, insulin secretion and hepatic glucose production. There is a range of antidiabetic treatment options now available to address these defects. Determination of which therapy for which patient is not always apparent from the clinical literature or the product information. OBJECTIVE: To summarise the extent and use of clinical evidence, clinical practice and pharmacoeconomics in positioning antidiabetic agents in Australian clinical practice. DISCUSSION: This paper summarises the introduction of new agents into the options for treatment of type 2 diabetes through the Pharmaceutical Benefits Scheme. Combining evidence based medicine, accepted clinical practice and decision analysis, allows the controlled introduction of new therapies in a climate of limited resources and a population with increasing therapeutic needs.

Australia↗