Diabetes and Endocrinology

Alogliptin is a highly selective DPP-IV inhibitor under investigation for the treatment of type 2 diabetes. An NDA for alogliptin was submitted in January 2008, and a response from FDA is expected in the fourth quarter of this year.

Drug Watch: Agents in late-stage development for the treatment of types 1 and 2 diabetes mellitus (September 2008)

A recent multinational, randomized, double-blind, placebo-controlled clinical trial demonstrated that administration of aliskiren provides additional renal protection to patients with hypertension, type 2 diabetes mellitus, and nephropathy who are already receiving optimal antihypertensive therapy and renal protective therapy with the angiotensin receptor blocker (ARB) losartan.

Among the new data presented at the 68th Scientific Sessions of the ADA were the results of phase 3 trials of the investigational agents liraglutide, ABT-335, saxagliptin, and alogliptin.

Drug Watch: Agents in late-stage development for the treatment of type 2 diabetes mellitus (August 2008)

Lacosamide safely decreases pain scores in patients with painful diabetic neuropathy, according to a pooled efficacy and safety analysis presented at the 60th Annual Meeting of the American Academy of Neurology, Chicago.

Treatment of diabetes with DPP-IV inhibitors; sitagliptin, vildagliptin, alogliptin, and saxagliptin.

Colesevelam (Welchol) was approved on January 18, 2008, as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes.

The use of rosiglitazone to treat type 2 diabetes in older patients has been associated with an increased risk of cardiovascular events.

In a multicenter, multinational, randomized controlled study, a fixed-dose combination of perindopril/ indapamide was associated with a reduced risk of death and vascular events in patients with type 2 diabetes, many of whom were already taking antihypertensive drugs.

An extensive systematic review published in the Annals of Internal Medicine demonstrated that older oral drugs for type 2 diabetes are just as, if not more, effective than newer agents for gylcemic control, lipid control, and other intermediate end points.

Nebivolol, an investigational (NDA submitted) vasodilating beta-blocker, demonstrated a neutral effect on blood glucose levels in two 12-week clinical studies of patients with hypertension.

Investigators have demonstrated that patients with type 2 diabetes who use inhaled insulin as part of their basalbolus insulin regimen experience a small decline in pulmonary function.

An open-label extension study of exenatide demonstrated sustained blood glucose control and weight loss in patients with type 2 diabetes.

A quick-release formulation of bromocriptine reduces the incidence of diabetic cardiovascular complications in patients with type 2 diabetes and improves glycemic control in those patients who did not achieve HbA1c <7.5% with metformin plus a sulfonylurea.

Statins and fibrates reduce the risk of peripheral neuropathy in patients with type 2 diabetes independent of the agents' effects on lipids, according to results presented at the 67th annual scientific sessions of the American Diabetes Association.

The use of pioglitazone in patients with renal dysfunction, type 2 diabetes, and macrovascular disease can reduce the risk of death, nonfatal myocardial infarction (MI), and stroke according to results presented at the 67th annual scientific sessions of the American Diabetes Association.

Rosiglitazone did not demonstrate an increased risk of hospitalizations and death from cardiovascular causes (the composite end point) in an interim analysis of a prospective study.

Results of a double-blind, randomized, contolled trial of vildagliptin versus rosiglitazone demonstrate similar efficacy and tolerability in patients with type 2 diabetes.

Incretin mimetic approved as adjunctive therapy in type 2 diabetes mellitus not adequately controlled by a thiazolidinedione

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have developed a consensus algorithm for the management of hyperglycemia in type 2 diabetes. The statement, published in the August issue of Diabetes Care, was created for several reasons.

In a randomized, double-blind, placebo-controlled trial recently published in Lancet, the thiazolidinedione (or "glitazone") rosiglitazone statistically significantly reduced the incidence of new-onset diabetes when given to patients diagnosed with prediabetes but lacking a prior history of cardiovascular disease. The benefits of using thiazolidinediones in the treatment of patients with diabetes are well known, but the current finding that thiazolidinediones can prevent prediabetics from progressing to diabetes is novel.

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.