Biomedical subjects

Sandra L Cox

Publications and source records attributed to Sandra L Cox.

6 recordsLinked to original sources

PubMed2006

Tesaglitazar: a promising approach in type 2 diabetes.

While glycemic control remains the cornerstone of clinical management for patients with type 2 diabetes, the importance of a more comprehensive approach that addresses the multiple metabolic abnormalities seen in this population is now widely recognized. Abnormal lipid metabolism resulting in dyslipidemia contributes greatly to the markedly increased risks of cardiovascular disease observed in diabetic patients and in prediabetic patients with signs of insulin resistance. The peroxisome proliferator-activated receptors (PPARs) play a key role in the regulation of energy homeostasis and the coordination of inflammatory responses. As such, they are interesting targets for addressing both the glucose and lipid abnormalities associated with insulin resistance. The thiazolidinediones (TZDs), which activate PPARgamma, appear to improve glycemic control primarily by increasing peripheral insulin sensitivity and reducing hepatic glucose production, thereby helping to preserve beta-cell function. They have also demonstrated modest beneficial effects on some lipid parameters. The fibrate drugs, which activate PPARalpha, produce robust improvements in dyslipidemia, decrease atherosclerotic lesions and may have an effect on cardiovascular events, but do not affect glycemia. Theoretically, a compound targeting both the alpha and gamma PPARs simultaneously might combine the benefits of TZDs and fibrates. Tesaglitazar is a dual-acting PPARalpha/gamma agonist currently being investigated in phase III clinical trials as an alternative treatment for insulin resistance and the characteristic dyslypidemia of type 2 diabetes. This article reviews the available data on the clinical efficacy and safety of tesaglitazar in patients with type 2 diabetes and in individuals without diabetes but with insulin resistance.

Alkanesulfonates↗

PubMed2005

Emtricitabine: a novel nucleoside reverse transcriptase inhibitor.

Emtricitabine is a once-daily nucleoside reverse transcriptase inhibitor (NRTI) that selectively and potently inhibits human immunodeficiency virus type 1 (HIV-1) replication. Emtricitabine is used in combination with other antiviral agents for the treatment of HIV-1 and is currently under investigation for the treatment of hepatitis B virus (HBV) infection. Like other NRTIs, emtricitabine is activated to a triphosphate derivative, which mediates the antiviral effect. Emtricitabine triphosphate is incorporated into a primer DNA strand resulting in chain termination and blockade of DNA- or RNA-directed DNA synthesis. One key benefit of emtricitabine over other NRTIs is its favorable pharmacokinetic profile that permits once-daily dosing; it has a long mean plasma elimination half-life of 8-10 hours, and the intracellular half-life of emtricitabine triphosphate is 39 hours after multiple doses of 200 mg daily. In adult patients infected with HIV-1, emtricitabine has a convenient and simple dosing schedule of one 200-mg capsule once daily, and is as effective as lamivudine 150 mg twice daily and more effective than stavudine twice daily at suppressing plasma HIV-1 RNA when administered as part of a triple-drug regimen. Also, triple therapy including emtricitabine is as effective as a protease inhibitor- based regimen in maintaining durable suppression of plasma HIV-1 RNA levels in adults. Early clinical results show that triple therapy including emtricitabine is also effective in decreasing or maintaining durable suppression of HIV-1 RNA levels in children and adolescents with HIV-1 infection. It is also effective against HBV in patients co-infected with HIV-1 and in patients monoinfected with HBV. In clinical practice, emtricitabine is generally very well tolerated, with most adverse events being mild to moderate in severity. The now available combination of emtricitabine with tenofovir in the same pill makes it a very attractive backbone combination to use in conjunction with other antiretroviral drugs.

Adult↗

PubMed2005

Insulin glulisine.

In patients with diabetes, the benefit of conventional insulin therapy can be limited due to difficulty in achieving tight glycemic control, which is critical to reducing the risk of long-term diabetes-related complications. The recent development of recombinant analogs of regular human insulin is changing the clinical management of diabetes. One of the newest members of this class of hypoglycemic agents is insulin glulisine, a rapid-acting insulin analog with a pharmacokinetic profile that more closely mimics the natural pattern of insulin secretion than regular human insulin. Subcutaneous administration of insulin glulisine has a faster subcutaneous absorption, a more rapid onset of activity, and a shorter duration of action than regular human insulin. These properties of insulin glulisine allow it to be administered shortly before or soon after meals by subcutaneous injection or by continuous subcutaneous pump infusion. Insulin glulisine effectively controls postprandial glucose excursions in both type 1 and type 2 diabetic patients without increasing the risk of hypoglycemia. One unit of insulin glulisine has the same glucose-lowering effect as one unit of regular human insulin. Insulin glulisine has a favorable safety profile, which is not significantly different from that of regular human insulin. This review summarizes the current data on the clinical efficacy and safety of insulin glulisine in type 1 and type 2 diabetic patients.

Animals↗

PubMed2005

Rimonabant hydrochloride: an investigational agent for the management of cardiovascular risk factors.

Rimonabant hydrochloride, the first drug in a new class of selective cannabinoid type 1 (CB1) receptor antagonists, is showing promise in clinical trials for the treatment of obesity and related metabolic risk factors, in addition to tobacco dependence. Results of phase III clinical trials comparing rimonabant with placebo found that overweight or obese patients, with or without untreated dyslipidemia or type 2 diabetes, lost significant body weight when treated with rimonabant 20 mg for a year. The weight loss was accompanied by a decrease in waist circumference, demonstrating a significant reduction in abdominal obesity, which is an independent marker for cardiovascular disease. Significant improvements were also observed in the lipid profile, with an increase in high-density lipoprotein (HDL) cholesterol and a decrease in triglyceride levels. Improvements in glucose tolerance and insulin levels were also found. Moreover, the number of patients diagnosed with the metabolic syndrome at baseline was significantly reduced. These beneficial effects of rimonabant 20 mg were maintained after 2 years of chronic treatment. Other phase III trials have shown that rimonabant helps people to quit smoking without significant post-cessation weight gain. Rimonabant has a favorable safety profile and is generally well tolerated. Rimonabant is proving to be a very promising approach for managing two major and preventable risk factors for cardiovascular disease. This review summarizes the available evidence on the clinical efficacy and safety of rimonabant as a potential therapy for obesity and smoking cessation.

Animals↗

PubMed2005

Muraglitazar: an agent for the treatment of type 2 diabetes and associated dyslipidemia.

Many studies indicate that postprandial metabolic abnormalities, such as hyperglycemia and dyslipidemia, which are exaggerated and prolonged in type 2 diabetes, are important risk factors for cardiovascular disease. Different pharmacotherapies have been developed to specifically target these risk factors associated with type 2 diabetes. The peroxisome proliferator-activated receptor (PPAR) agonists, which are potent insulin sensitizers, have been the focus of much research during the past decade. Since their development, PPAR agonists have emerged as an important target for the treatment of insulin resistance and dyslipidemia. The more recent development of agonists that selectively target both the alpha and gamma PPARs has provided a potential treatment of global risk in patients with the metabolic syndrome or type 2 diabetes. Muraglitazar is a non-thiazolidinedione, oxybenzylglycine dual PPARalpha/gamma agonist that is in advanced clinical development for the treatment of type 2 diabetes and its associated dyslipidemia. This article summarizes the available clinical data on the efficacy and safety of muraglitazar in patients with type 2 diabetes.

Adult↗

PubMed2004

Rosiglitazone maleate/metformin hydrochloride: a new formulation therapy for type 2 diabetes.

Many patients with type 2 diabetes require treatment with more than one antihyperglycemic drug to achieve optimal glycemic control. The thiazolidinediones are a novel class of oral antihyperglycemic drugs that improve glycemic control primarily by increasing peripheral insulin resistance and sensitizing the skeletal muscle, liver and adipose tissue to the actions of insulin, in addition to improving beta-cell function. One of the many features of the thiazolidinedione class of drugs is their synergism with other antihyperglycemic drugs that have a different mechanism of action. The combination of metformin hydrochloride, a biguanide that enhances glucose uptake in peripheral tissues and reduces hepatic gluconeogenesis, with rosiglitazone maleate, one of the newly available members of the thiazolidinedione family, offers a rational therapeutic approach to the treatment of type 2 diabetes. In patients whose type 2 diabetes is inadequately controlled with metformin monotherapy, the addition of rosiglitazone significantly improves glycemic control, insulin sensitivity and beta-cell function, compared with either drug alone. In addition, this combination therapy has beneficial effects on other cardiovascular risk factors. Rosiglitazone maleate/metformin hydrochloride combination therapy is well tolerated in patients with type 2 diabetes and has a favorable safety profile. This review summarizes the available evidence on the clinical efficacy and safety of rosiglitazone maleate and metformin hydrochloride combination therapy in patients with type 2 diabetes.

Blood Glucose↗