A new study has found that the diabetes drug Avandia puts patients at a higher risk of death and heart failure than the rival diabetes drug Actos.

Avandia, from GlaxoSmithKline, has been under a lot of scrutiny as of late due to safety issues tied to it.

Researchers have found that older diabetics are better off taking the drug Actos from Takeda Pharmaceuticals, as it carries a lower risk of death and heart failure with it.

The drugs are in the same class and were put together for a head-to-head comparison.

This confirmed past research which revealed that the drug Avandia was more risky.

The study found no difference in the risk of heart attack and stroke.

They did find though that those in the Avandia group had higher risks of death and heart failure.

The study was led by Dr. Wolfgang Winkelmayer of the Brigham and Women’s Hospital in Boston and was published in the Archives of Internal Medicine.

Main article: Diabetes mellitus type 1

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated variety, where beta cell loss is a T-cell mediated autoimmune attack.[3] There is no known preventive measure which can be taken against type 1 diabetes; it is about 10% of diabetes mellitus cases in North America and Europe (though this varies by geographical location), and is a higher percentage in some other areas. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults but was traditionally termed “juvenile diabetes” because it represents a majority of the diabetes cases in children.

The principal treatment of type 1 diabetes, even in its earliest stages, is replacement of insulin combined with careful monitoring of blood glucose levels using blood testing monitors. Without insulin, diabetic ketoacidosis often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease. Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a bolus) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007. [9][10] Non-insulin treatments, such as monoclonal antibodies and stem-cell based therapies, are effective in animal models but have not yet completed clinical trials in humans.[11]

Type 1 treatment must be continued indefinitely in essentially all cases. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients, insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80“120 mg/dl, 4“6 mmol/l) as is safely possible. Some physicians suggest up to 140“150 mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 400 mg/dl (20 mmol/l) is sometimes accompanied by discomfort and frequent urination leading to dehydration. Values above 600 mg/dl (30 mmol/l) usually require medical treatment and may lead to ketoacidosis, although they are not immediately life-threatening. However, low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately.

[edit] Type 2 diabetes mellitus

Main article: diabetes mellitus type 2

Type 2 diabetes mellitus is characterized differently due to insulin resistance or reduced insulin sensitivity, combined with relatively reduced, and sometimes absolute, insulin secretion. The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. However, the specific defects are not known. Diabetes mellitus due to a known specific defect are classified separately.

In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses, the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary.

There are numerous theories as to the exact cause and mechanism in type 2 diabetes. Central obesity (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.[12] Other factors include aging (about 20% of elderly patients in North America have diabetes) and family history (type 2 is much more common in those with close relatives who have had it). In the last decade, type 2 diabetes has increasingly begun to affect children and adolescents, likely in connection with the increased prevalence of childhood obesity seen in recent decades in some places.[13] Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of polycarbonate plastic, and the incidence of type 2 diabetes.[14]

Type 2 diabetes may go unnoticed for years because visible symptoms are typically mild, non-existent or sporadic, and usually there are no ketoacidotic episodes. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure due to diabetic nephropathy, vascular disease (including coronary artery disease), vision damage due to diabetic retinopathy, loss of sensation or pain due to diabetic neuropathy, liver damage from non-alcoholic steatohepatitis and heart failure from diabetic cardiomyopathy.

Type 2 diabetes is usually first treated by increasing physical activity, decreasing carbohydrate intake, and losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. It is sometimes possible to achieve long-term, satisfactory glucose control with these measures alone. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral antidiabetic drugs. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication (often used in various combinations) can be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones). According to one study, overweight patients treated with metformin compared with diet alone, had relative risk reductions of 32% for any diabetes endpoint, 42% for diabetes related death and 36% for all cause mortality and stroke.[15] Oral medication may eventually fail due to further impairment of beta cell insulin secretion. At this point, insulin therapy is necessary to maintain normal or near normal glucose levels.

Since more then one-tenth of all health care expenditures in the United States in 2002 were attributable to diabetes, this finding raises important questions about whether the higher cost actually translates into improved care.

“Although more patients and more medications per patient played a role, the single greatest contributor to increasing costs is the use of newer, more expensive medications,” said lead author Caleb Alexander, MD, MS, assistant professor of medicine at the University of Chicago. “But new drugs don’t automatically lead to better outcomes.”

“Just because a drug is new or exploits a new mechanism does not mean that it adds clinically to treating particular diseases,” said co-author Randall Stafford, MD, PhD, associate professor at Stanford University School of Medicine. “And even if a new drug does have a benefit, it’s important to consider whether that benefit is in proportion to the increased cost.”

The researchers used two national data bases, one extending back to 1994, to assess trends in diabetes treatment. They found that the number of Americans diagnosed with diabetes rose steadily from 10 million in 1994, to 14 million in 2000, to 19 million in 2007.

This rapid growth reflects trends in American eating habits and behavior, the authors note, since the risk of developing type 2 diabetes increases with age, obesity, and physical inactivity. “Part of the increase is due to an increasingly sedentary lifestyle and increasing caloric intake,” said Stafford.

At the same time, the average number of medications per patient has increased from 1.06 medications per patient in 1994 to 1.45 medications per patient in 2007. In 1994, 82 percent of patients were prescribed only one drug; in 2007, only 47 percent were.

Meanwhile, the average price of a diabetes drug prescription increased from $56 in 2001 to $76 in 2007, due in large part to the rapid uptake of newly available oral medications, increasingly prescribed as alternatives to injectable insulin.

In 2007, for example, new drugs such as sitagliptin (brand name Januvia, $160 per average prescription) and exenatide (Byetta, $202) made up eight percent and four percent, respectively, of all physician office visits where a diabetes drug was prescribed. These drugs cost eight to 11 times more than older, generic drugs such as metformin or glypizide.

Although insulin use declined, the price per insulin prescription increased as new and pricier preparations of long-acting and ultrashort-acting insulins and their combinations gained popularity.

This diffusion of new therapies demonstrates the successful translation of research from bench to bedside, the author note. But they add that this study documents the rapid uptake of newer and more expensive drugs whose long-term safety and cost-effectiveness in broader populations is not known. “Without such long-term data,” said Alexander, “we cannot be certain if the widespread use of the costlier drugs is balanced by sufficient improvements in health.”

The study acknowledges that one indicator of benefit from diabetes drugs, average levels of the hemoglobin A1c blood test, improved between 1999 and 2004. Hemoglobin A1c reflects the three-month average of blood sugar and indicates how well this aspect of diabetes is being managed.

But short-term outcomes like better A1c levels don’t prove that patients with diabetes are actually benefiting from the new drugs in ways that matter, Alexander said. “They may not always correlate with long-term outcomes that people really care about, such as diabetes’ impact on heart and kidney function.”

Important long-term outcomes take many years to measure, Stafford said. “What we need are larger population studies examining the relative benefits of different drugs in treating diabetes and looking for these outcomes in people followed over an extended time period.” As a model, he pointed to the Women’s Health Initiative, a federal study that followed 162,000 women over 15 years to measure the effectiveness of treatments for heart disease, osteoporosis, and cancer.

(Published at Health News Track on October 27, 2008 – 1 day ago)