Diabetes and Endocrinology

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.

Orlistat (Xenical) in combination with diet and lifestyle changes significantly prevents obese patients from developing type 2 diabetes, say researchers involved in this 4-year study presented at the 9th International Congress on Obesity, Sao Paulo, Brazil. They add that this is the first time a weight loss drug has been shown to prevent or delay the onset of type 2 diabetes in an at-risk population.

The investigational inhaled insulin product (Exubera) could prove a boon to patients with diabetes, cutting or eliminating the need for injections. So indicate findings from a phase III trial presented at the annual meeting of the American Association of Clinical Endocrinologists (AACE). For patients with type 1 diabetes, a regimen of inhaled insulin before meals and one injection at night could control blood glucose as well as or possibly better than injections alone. These results add to some phase III data presented last June that showed a small but significant number of patients with type 2 diabetes reached recommended blood glucose levels at 6 months.

Therapy starting with the angiotensin receptor blocker (ARB) losartansignificantly reduced the risk of cardiovascular outcomes and new-onsetdiabetes compared with a beta blocker in older high-risk hypertensive patients,said Björn Dahlöf, MD. The improved outcomes with losartan occurredeven after adjusting for small differences in blood pressure reduction betweenthe two study drugs.

For the first time, a large clinical trial has shown that a medication can help prevent type 2 diabetes in high-risk individuals. At the same time, drug therapy emerged as a less effective preventive strategy than fairly modest diet and exercise changes.