Diabetes

In a randomized, double-blind, placebo-controlled trial, the angiotensin-converting enzyme (ACE) inhibitor ramipril, when administered to patients with prediabetes but no previous cardiovascular disease, failed to demonstrate a statistically significant reduction in the primary composite end point of new-onset diabetes or death.

Obesity is on the rise in the United States, with 60.5% of the adult population overweight and 23.9% obese as of 2005. Up to 10% of an industrialized country's healthcare budget often can be spent on obesity and associated comorbidities.

Patients taking clozapine for schizophrenia should be regularly monitored because of an increased risk for metabolic abnormalities, according to a study published in the American Journal of Psychiatry.

Approximately 17 million people in the United States have type 2 diabetes, and the prevalence continues to rise.1 More than 45% of patients with end-stage renal disease have type 2 diabetes as an etiology, and a patient with type 2 diabetes has the same risk of developing an acute coronary syndrome (unstable angina, myocardial infarction [MI]) over the next 10 years as someone who has had an acute coronary syndrome in the past.2 In addition to these complications, type 2 diabetes also increases the risk of blindness, neuropathy, and amputation.3

Despite the variety of medications available to treat type 2 diabetes, the disease is inadequately controlled in many patients. In order to improve glycemic control, manufacturers are pursuing compounds that affect the incretin hormones that stimulate insulin release in response to increased glucose levels. Although stimulation of the incretin receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, the clinical usefulness of GLP-1 is limited by its rapid degradation by dipeptidyl peptidase-IV (DPP-IV). Drug companies have developed compounds intended to act as inhibitors of DPP-IV. Vildagliptin (Galvus, Novartis) is the second DPP-IV inhibitor under investigation by FDA to offer this new mechanism to achieve glycemic control. An NDA for vildagliptin was submitted to FDA in March 2006, 1 month after the submission of the first DPP-IV inhibitor, sitagliptin.

Three studies presented at the 10th International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain, yielded new data regarding the relationship between diabetic and pre-diabetic conditions and the subsequent development and treatment of Alzheimer's disease (AD).

Intensive therapy with atorvastatin 80 mg/d, in comparison with the same medication at 10 mg/d, significantly reduced the rate of major cardiovascular events by 25% in patients with clinically evident stable coronary heart disease (CHD) and diabetes, according to a study published in Diabetes Care.

Atorvastatin showed no statistically significant difference in the reduction of a composite cardiovascular disease (CVD) end point in type 2 diabetes patients, according to a randomized, double-blind, parallel-group study.

A variety of clinical approaches are utilized in the management of poor glycemic control in patients with type 2 diabetes. Sitagliptin (Januvia, Merck), a novel drug in a new medication class known as dipeptidyl peptidase-IV (DPP-IV) inhibitors, offers a new mechanism by which to achieve glycemic control. Although stimulation of receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, rapid degradation of GLP-1 by DPP-IV limits its clinical effectiveness. The development of medications to reduce this degradation is being pursued by numerous manufacturers. An NDA for the first of these medications, sitagliptin, was submitted to FDA in February 2006. Currently available clinical studies have demonstrated improved glycemic control with sitagliptin therapy in patients who have not achieved target glucose levels with diet and oral medications. (Formulary. 2006;41:434–441.)

The anticonvulsant lacosamide is effective in relieving diabetic neuropathy and produces increased pain reduction with continued treatment for 22 months, according to phase 3 study results presented during the 25th Annual Scientific Meeting of APS in San Antonio, Texas. "This is a promising treatment that maintains a long-term effect," said Tibor Hidvegi, MD, Medical Department, Petz Hospital, Gyor, Hungary.

Tight glucose control for a mean period of 6.5 years produces long-lasting cardiovascular benefits in patients with type 1 diabetes, according to a study published in the New England Journal of Medicine (NEJM).

Although experience tells us that formulary conversion programs are commonplace, they are discussed fairly infrequently in the literature. A recent MEDLINE search did not identify any conversion programs similar to a human growth hormone (HGH) program implemented at HIP Health Plan of New York (HIP-NY).

New inhalable insulin formulation approved

Diabetic peripheral neuropathy, one of the most common late complications of diabetes, is associated with decreased quality of life and increased morbidity. The pathophysiology of diabetic neuropathy (DN) is multifactorial, contributing to ischemic and painful events and neuronal damage.

In an observational study of patients with type 2 diabetes being treated for heart failure, researchers found that metformin—whether used alone in vulnerable patients or in combination—is associated with lower mortality, less morbidity, and fewer hospitalizations compared with sulfonylurea monotherapy. The study, conducted in Canada, was published in Diabetes Care.

ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) possess a similar and significant ability to reduce the development of new-onset type 2 diabetes among patients with hypertension, coronary artery disease, and heart failure, according to a meta-analysis study published in Diabetes Care.

Inhaled insulin (Exubera, Pfizer/Sanofi-Aventis) could be an effective therapy and alternative to rosiglitazone (Avandia, GlaxoSmithKline) for individuals who are early into the course of type 2 diabetes, according to a study published in Diabetes Care.

Phase 3 clinical trial results have demonstrated that the dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist muraglitazar achieves significant beneficial lipid effects compared with pioglitazone, and the agent also provides long-term glycemic control in type 2 diabetics. The results were reported during the American Diabetes Association (ADA) 65th Annual Meeting in San Diego, Calif.

Phase 3 clinical trial results have demonstrated that the dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist muraglitazar achieves significant beneficial lipid effects compared with pioglitazone, and the agent also provides long-term glycemic control in type 2 diabetics. The results were reported during the American Diabetes Association (ADA) 65th Annual Meeting in San Diego, Calif.

First-in-class approved for type 2 diabetes

The use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure (HF). However, the risk does not extend beyond the first year after diagnosis and does not appear to differ among the types of drug therapy, according to researchers who assessed 25,680 patients in the UK General Practice Research Database between 1988 and 1999. The researchers categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (OHA), and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin.

Although oral antidiabetic medications initially may be effective for controlling hyperglycemia, these agents often fail to maintain adequate glycemic control as the disease progresses, and insulin eventually is required in most patients. This review explores strategies for identifying patients with type 2 diabetes who are failing to maintain glycemic control on oral agents and for transitioning these patients to insulin. Based on available data, patients are not reaching recommended glycemic goals due to delays in and reluctance towards intensification of therapy, resulting in an increased risk of complications.

A number of clinical approaches are utilized in managing the overlapping aspects of poor glycemic control in patients with type 2 diabetes. Exenatide (Amylin/Lilly), a novel drug in a new medication class known as the incretin mimetic agents, offers a new mechanism to achieve glycemic control.

A number of clinical approaches are utilized in managing the overlapping aspects of poor glycemic control in patients with type 2 diabetes. Exenatide (Amylin/Lilly), a novel drug in a new medication class known as the incretin mimetic agents, offers a new mechanism to achieve glycemic control.

Once-daily injections of liraglutide, a long-acting, acylated, glucagon-like peptide 1 analog, have proven to be effective in the treatment of patients with type 2 diabetes.

Two studies evaluating the efficacy and long-term safety of the inhalable, rapid-acting dry powder insulin formulation (Exubera, Pfizer/Aventis) demonstrate that the drug was able to sustain glycemic control and pulmonary function in patients with type 2 diabetes

A recent study found that atorvastatin at its starting dosage reduces the risk of a first major cardiovascular event in patients with type 2 diabetes, said Helen Colhoun, MD, at the 64th scientific sessions of the American Diabetes Association (ADA) in Orlando.

Patients with diabetes are at extremely high risk for cardiovascular disease. Because glucose control is associated with only modest reductions in macrovascular complications, efforts must be made to specifically target other cardiovascular risk factors. Diabetes is associated with a characteristic lipid profile: low high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels with or without high low-density lipoprotein cholesterol (LDL-C) levels. This profile is also found in patients with early-onset coronary heart disease and correlates with increased atherogenesis. Multiple clinical trials have demonstrated that lipid-modifying therapy in patients with diabetes decreases cardiovascular risk. Management targeting all lipid abnormalities may represent the best treatment strategy since many patients with diabetes do not have elevated LDL-C levels. Combining lipid-modifying agents is also an attractive option for normalizing multiple lipid abnormalities. (Formulary 2003;38:478-497)

Premeal dosing of inhaled insulin may represent a valuable option for patients with type 2 diabetes.