Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin is an effective agent in the oral treatment of non-insulin-dependent diabetes mellitus and does not cause hypoglycemia like the sulfonylureas. This drug is safe provided the cautions and contraindications are followed and the patient is monitored for hepatic and renal function. Metformin is used extensively outside the United States in the treatment of type II diabetes and recently was approved by the FDA for marketing under the brand name of Glucophage.
Diabetes Educ
PMID:Metformin: a biguanide. 893 23

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of metformin hydrochloride are reviewed. Metformin is an antihyperglycemic agent; it lowers the blood glucose concentration without causing hypoglycemia. Proposed mechanisms of action include decreased intestinal absorption of glucose, increased glucose uptake from the blood into the tissues, decreased glucose production in the liver, and decreased insulin requirements for glucose disposal. Metformin is slowly absorbed from the small intestine and does not undergo hepatic metabolism. The half-life is about five hours. The major route of elimination is renal; the drug is contraindicated in patients with impaired renal function. In double-blind, placebo-controlled trials, metformin has shown efficacy in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). The drug is as effective as sulfonylureas in patients with diabetes who are nonobese or obese and whose diabetes is uncontrolled by diet alone. Metformin may be useful as addon therapy in obese patients with diabetes uncontrolled by sulfonylureas and diet. Lipid profiles may be favorably influenced. The most common adverse effects are gastrointestinal. A rare but potentially fatal adverse effect is lactic acidosis. Metformin has the potential to interact with cationic drugs eliminated by the renal tubular pathway. The usual effective dosage is 1.5-2.5 g/day orally in two or three divided doses. Metformin hydrochloride is an effective alternative to sulfonylureas in obese and non-obese patients with NIDDM in whom diet alone has not achieved glycemic control, and it may be useful as addon therapy in patients whose diabetes has not responded adequately to sulfonylureas plus dietary measures.
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PMID:Metformin hydrochloride: an antihyperglycemic agent. 911 21

The Diabetes Prevention Program is a new, 150 million dollar, NIH-sponsored study designed to determine whether non-insulin-dependent diabetes mellitus can be prevented or delayed in persons with impaired glucose tolerance. Four thousand subjects will be randomly assigned to one of four study groups and followed for 4.5 years. Study groups include intensive lifestyle intervention with diet and exercise; metformin (Glucophage) or troglitazone (an investigational drug) with standard diet and exercise; and a control group. Insulin resistance is an important pathogenic factor in impaired glucose tolerance. Trivalent chromium, a dietary supplement that potentiates the action of insulin, was not included in the program. Like metformin and troglitazone, trivalent chromium decreases insulin resistance and has an acceptable side-effect profile; furthermore, it is available at a fraction of their cost. Trivalent chromium should have been included in the Diabetes Prevention Program; it is unfortunate that it was omitted.
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PMID:Trivalent chromium and the diabetes prevention program. 924 7

Recently there has been growing interest in studying the differences between different classes of antihypertensive drugs in preventing cardiovascular events in diabetic patients. Hypomagnesemia is common in diabetes mellitus, and correlates to its chronic complications and the associated alteration of the antioxidant enzyme activity. Depletion of reduced glutathione (GSH) in the blood has been demonstrated with myocardial injuries associating hypomagnesemia. A previous study has demonstrated a beneficial effect of metformin hydrochloride (Met), an antihyperglycemic drug, on both magnesium (Mg) and GSH levels in diabetic animals. The purpose of this study was to investigate the effect of oral atenolol, metformin (50 and 60 mg kg[-1] day[-1], respectively) and their combination for 14 days on Mg and GSH levels in blood, liver and heart of diabetic male Wistar rats, as these two parameters have been shown to be altered in diabetics and linked to myocardial ischemic injuries. The results of this investigation showed a state of low levels of Mg and GSH in both blood and liver of the diabetic animals. Treatment with atenolol alone did not change these levels significantly, however administration of metformin or atenolol/metformin increased significantly the GSH levels in both liver and blood, and returned the liver Mg content back to normal values.
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PMID:Influence of atenolol and/or metformin on glutathione and magnesium levels in diabetic rats. 941 50

Recently, the number of agents to treat type 2 diabetes has increased markedly. In the past, the only agents practitioners had available to treat patients with type 2 diabetes mellitus were insulin and sulfonylureas. Today, three additional classes of agents with a total of six new drugs are available: acarbose, migital, repaglinide, metformin hydrochloride, troglitazone, and rosiglitazone. In the not-too-distant future, several other agents will be available for treating patients with diabetes. These new agents will allow physicians to control their diabetic patients' blood sugar levels without the need for insulin injections. This article reviews the new agents and provides practical suggestions regarding their use as monotherapy or in combination therapy.
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PMID:Pharmacologic management of diabetes mellitus. 1065 25

In type II diabetes treated with metformin (Glucophage) lactic acidosis is a rare adverse reaction, fatal in approximately 50 per cent of cases. Metformin is implicated by plasma and intra-erythrocyte levels. An analysis is carried out on available information about this risk for healthcare professionals and for patients. A comparison is made of approved labelling information on Glucophage and its patient leaflets in France and in the USA and an analysis made of the differences. In France, Information given to physicians, pharmacists and patients on the risk of lactic acidosis where Glucophage is implicated must be improved, and on the interest of the metformin plasma level in this case. These are primary points because the issue for the few patients concerned may be fatal. Advice on self-medication may be introduced. The evolution of information provided on these risks depends on the pharmaceutical laboratory, government authorities and healthcare professionals.
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PMID:[Lactic acidosis and metformin implicated: why better information about risk factors?]. 1096 1

Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with DepoMed for the treatment of diabetes. In May 2002, DepoMed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail would pay a $25 million milestone fee upon approval and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued DepoMed shares for $12.3 million. Biovail has subsequently developed a 1000mg dose of metformin extended release. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Metformin GR is available for partnership in Europe and Asia (Bio-Square-2004, Basel, Switzerland). In April 2004, Depomed and Biovail filed an NDA with the US FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza), 500mg and 1000mg tablets. The 500mg dosage was developed by Depomed using its patented drug delivery GR technology, while Biovail developed the metformin 1000mg dose using its proprietary Smartcoat delivery technology. Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated haemoglobin level similarly to that of metformin immediate release. Biovail successfully compared the metformin extended release 1000mg dose with Depomed's 500mg dose in multiple equivalence studies. In these studies, metformin extended release was well tolerated and demonstrated an excellent safety profile in terms of gastrointestinal adverse events. The licensee, Biovail, has submitted an application for metformin extended release with Health Canada. Bristol-Myers Squibb is marketing a proprietary, once-daily extended-release formulation of metformin (Glucophage XR). Several companies are developing controlled-release and extended release formulations of metformin.
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PMID:Metformin extended release--DepoMed: metformin, metformin gastric retention, metformin GR. 1523 Jun 31

In the new oral, once-daily, extended-release (ER), single-composition osmotic tablet formulation of the biguanide metformin hydrochloride (metformin XT), metformin is released at a controlled rate from a central osmotic tablet core through a semipermeable coating. A decrease in fasting plasma insulin, a marker of insulin resistance, was seen with metformin XT but not with immediate-release (IR) metformin in one well designed trial, but changes were similar in another. The pharmacokinetics of metformin XT reflect its extended-release characteristics. While the bioavailability (in terms of area under the plasma concentration-time curve) of metformin XT taken after the evening meal is similar to that of the IR formulation taken in divided doses, time to peak plasma concentrations is prolonged. Increases in metformin XT dose from 1000mg to 2500mg resulted in predictable and consistent dose-associated increases in metformin exposure. As with other ER metformin formulations, the bioavailability of metformin XT is increased after food, in contrast to the slight decrease seen with the IR formulation. The efficacy of metformin XT 1000, 1500, 2000, or 2500mg once daily with the evening meal was found not inferior to a similar dose range of metformin IR given in divided doses (measured by changes in glycosylated hemoglobin [HbA(1c)]) in a well designed study of 659 evaluable patients with type 2 (non-insulin-dependent) diabetes mellitus previously stabilized on metformin IR. Metformin XT and IR 2000 or 2500 mg/day had clinically similar efficacy (using changes in HbA(1c) and fasting plasma glucose) in another well designed study of 102 evaluable patients with type 2 diabetes. Like the IR formulation, metformin XT is generally well tolerated; gastro-intestinal adverse events are, however, common.
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PMID:Extended-release metformin hydrochloride. Single-composition osmotic tablet formulation. 1533 Jun 82

Beyond its antidiabetic activity justifying its use in the treatment of the type 2 diabetes, metformin (MET [dimethylguanidine, Glucophage]) has been shown to exhibit antioxidant properties in vitro, which could contribute to limit the deleterious vascular complications of diabetes. We investigated whether MET, at the pharmacological level of 10 -5 mol/L, was able to modulate intracellular production of reactive oxygen species (ROS) both in quiescent bovine aortic endothelial cells (BAECs) and in BAECs stimulated by a short incubation with high levels of glucose (30 mmol/L, 2 hours) or angiotensin II (10 -7 mol/L, 1 hour). Intracellular ROS production was measured by fluorescence of the DCF (2,7-dichlorodihydrofluorescein) probe. Our results showed that MET was able to reduce the intracellular production of ROS in both nonstimulated BAECs (-20%, P < .05) and BAEC stimulated by high levels of glucose or angiotensin II (-28% and -72%, respectively, P < .01). Experiments performed in the presence of the nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase inhibitor apocynin or the respiratory mitochondrial chain inhibitor rotenone indicated that MET exerted its effect partly through an inhibition of the formation of ROS produced mainly by NAD(P)H oxidase and also, to a lesser extent, by the respiratory mitochondrial chain.
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PMID:Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells. 1593 22

A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.
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PMID:Design and evaluation of compound metformin/glipizide elementary osmotic pump tablets. 1596 39


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