Diabetes Drugs May Be Related To Fracture Risk

April 28, 2008

April 18, 2008 (EurekAlert) - A widely used class of diabetes medications appears to be associated with an increased risk for fractures, according to a report in the April 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“The insulin-sensitizing thiazolidinediones are a relatively new and effective class of oral antidiabetic agents that have gained wide use in clinical conditions characterized by insulin resistance,” the authors write as background information in the article. Two drugs in this category, pioglitazone and rosiglitazone, account for 21 percent of oral diabetes medications prescribed in the United States and 5 percent of those in Europe. Recent studies have suggested that these therapies may have unfavorable effects on bone, resulting in slower bone formation and faster bone loss.

Christian Meier, M.D., of University Hospital Basel, Basel, Switzerland, and colleagues studied 1,020 patients with diabetes who had fractures diagnosed at British general practitioners’ offices between 1994 and 2005. For each of those patients, up to four control patients with diabetes who were the same age and sex and had the same physician but did not have fractures were selected, for a total of 3,728 matched controls.

After adjusting for other risk factors, individuals who were currently taking rosiglitazone and pioglitazone had approximately double or triple the odds of hip and other non-spine fractures than those who did not take these drugs. The odds for fracture were increased among patients who took the drugs for approximately 12 to 18 months and the risk was highest for those with two or more years of therapy.

“This analysis provides further evidence of a possible association between long-term use of thiazolidinediones and fractures, particularly of the hip and wrist, in patients with diabetes mellitus,” the authors conclude. “No such effect was seen for other antidiabetic drugs in this study population. These findings, although they are consistent with recently reported data from a randomized trial, are based on relatively few thiazolidinedione-exposed patients and need to be confirmed by additional observational studies and by controlled clinical trials.”

Posted by dlife at 10:22 AM | Comments (0)

Aspirin-Like Compounds Increase Insulin Secretion in Otherwise Healthy Obese People

April 26, 2008

April 26, 208 (Newswise) — Aspirin-like compounds (salicylates) can claim another health benefit: increasing the amount of insulin produced by otherwise healthy obese people. Obesity is associated with insulin resistance, the first step toward type 2 diabetes.

Aspirin and other salicylates are known to reduce blood glucose in diabetic patients. New research accepted for publication in the Journal of Clinical Endocrinology & Metabolism reveals a similar beneficial effect among obese individuals by increasing the amount of insulin secreted into the bloodstream.

“The administration of a salicylate led to the lowering of serum glucose concentrations,” said Jose-Manuel Fernandez-Real of the Institut d’Investigacio Biomedica de Girona and CIBEROBN Fisiopatologia de la Obesidad, Spain, and lead author of the study. “These findings highlight the importance of further research on the possible therapeutic benefit of aspirin in the fight against type 2 diabetes.”

For their study, Fernandez-Real and his colleagues evaluated the effects of triflusal (a derivative of salicylate) on 28 subjects (nine men and 29 women). The average age of the participants was 48 years old and their average Body Mass Index (BMI) was 33.9. A BMI of over 30 is considered obese. During three, four-week treatment periods, the study participants received a 600 mg dose, a 900 mg dose, or a placebo once per day.

The researchers found that administration of triflusal led to decreased fasting serum glucose. Contrary to their expectations, insulin sensitivity did not significantly change during the trial. Insulin secretion, however, significantly increased in relation to the dose size.

In conjunction with the human studies, the researchers also conducted laboratory studies on insulin-producing cells (known as islets of Langerhans) from mice and humans. The researchers observed that triflusal significantly increased the insulin secreted by these cells.

“Aspirin therapy has been recognized to improve glucose tolerance and to reduce insulin requirements in diabetic subjects,” said Fernandez-Real. “To our knowledge, this is the first study to show that salicylates lowered serum glucose in non-diabetic obese subjects. We believe that this effect was due to a previously unsuspected increase in insulin secretion rather than enhanced insulin sensitivity.”

The paper “Salicylates increase insulin secretion in healthy obese subjects” will appear in the July issue of JCEM, a publication of The Endocrine Society.”

Other researchers involved in the study include Abel Lobez-Mermejo, Ana-Belen Ropero, Sandra Piquer, Angel Nadal, Judit Bassols, Roser Casamitjana, Roman Gomis, Eva Arnaiz, Inaki Perez, and Wifredo Ricart.

Posted by dlife at 10:29 AM | Comments (0)

Potential Drug Target Identified for Diabetes

April 09, 2008

April 9, 2008 (Newswise) — Scientists at the Toronto General Hospital Research Institute have discovered a novel signaling pathway between three organs – the gut, the brain, and the liver – which lowers blood sugar when activated.

A team led by Dr. Tony Lam used a rat model to discover that fats can activate a subset of nerves in the intestine, which then send a signal to the brain and subsequently to the liver to lower glucose or sugar production. But eating a high-fat diet for just three days can interfere with this signal, disabling it so that it does not signal the other organs to lower blood glucose levels.

The research was published in a paper entitled, “Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production” as an advance on-line publication of the international science journal Nature.

“This is a new approach in developing more effective methods to lower glucose or blood sugar levels in those who are obese or have diabetes,” said Dr. Lam, who holds The John Kitson McIvor (1915 – 1942) Chair in Diabetes Research at the University Health Network and University of Toronto. Currently, those with diabetes lower their glucose through diet, exercise, anti-diabetic tablets or insulin injections (usually several times a day) and must regularly monitor blood glucose levels. High glucose levels can result in damage to eyes, nerves and kidneys and increase the risk of heart attack, stroke, blindness, erectile dysfunction, foot problems and amputations. Many laboratories around the world are in a race to find alternative and effective ways in which to lower glucose levels because of the severe complications which can result from high sugar levels.

“We already knew that the brain and liver can regulate blood glucose levels, but the question has been, how do you therapeutically target either of these two organs without incurring side effects?” noted Dr. Lam, who is also an Assistant Professor of Physiology and Medicine at the University of Toronto. “We may have found a way around this problem by suggesting that the gut can be the initial target instead. Much like a remote control device, the gut is able to relay a signal to the brain which in turn signals the liver to lower glucose production. If new medicines can be developed that stimulate this sensing mechanism in the gut, we may have an effective way of slowing down the body’s production of sugar, thereby lowering blood sugar levels in diabetes.”

Dr. Lam emphasized that it will take a number of years of experimental work to determine whether this approach is effective and safe in humans who have diabetes.

More than two million Canadians have diabetes. “Diabetes is an epidemic in Canada and around the world and its numbers are continuing to increase at an alarming rate, consuming our precious health care resources,” says Dr. Gary Lewis, Head of the Division of Endocrinology and Metabolism at the University Health Network and Mount Sinai Hospitals in Toronto and Professor of Medicine and Physiology at the University of Toronto. “We have good evidence from clinical trials which shows that lowering blood glucose levels towards normal in those who develop diabetes has a major impact in preventing its devastating complications, so it is critical that we learn how to control these levels in the most effective and least invasive ways possible. Dr. Lam’s work reveals a new regulatory circuit which provides novel sites and targets to lower these levels in diabetes and obesity.”

Dr. Richard Weisel, Director of the Toronto General Research Institute (TGRI), Professor and Chairman of Cardiac Surgery at the University of Toronto, welcomes any potential interventions which can help lower blood sugar levels. “Studies have shown that people with very high blood glucose levels are more likely to die from heart disease, so anything that we can discover to help lower these levels would help in decreasing the progression of and mortality from cardiovascular disease.”

"Tony's discovery represents an exciting breakthrough that could eventually lead to new ways to treat diabetes," observed Dr. Diane Finegood, Scientific Director of the Institute of Nutrition, Metabolism and Diabetes, part of the Canadian Institutes of Health Research (CIHR). "I am pleased that CIHR played a major role in funding this research".

Working with rats, Dr. Lam and colleagues designed and performed a series of elegant experiments which showed for the first time that the lipids or fats which enter the small intestine trigger the afferent neuronal signal to the brain which then sends signals to the liver to lower glucose production and blood glucose levels in as little as fifteen minutes. No drop in levels occurred when nerves were cut or blocked between the gut and the brain or between the brain and the liver. The trigger to lower glucose was also disabled when rats were fed a high-fat diet for three days prior to the experiment, a finding which may suggest that those who eat a high fat diet lose this beneficial signaling pathway.

Other researchers involved in the study include Penny Wang, Liora Caspi, Carol Lam, Madhu Chari and Michelle Ang from TGRI; Xiaosong Li, Roger Gutierrez-Juarez and Gary Schwartz from Albert Einstein College of Medicine; Peter Light from University of Alberta.

The work was funded by the Canadian Institute of Health Research.

About Toronto General Hospital, University Health Network
Toronto General Hospital is a partner in the University Health Network, along with the Toronto Western Hospital and the Princess Margaret Hospital. These research hospitals are affiliated with the University of Toronto. The scope of research at Toronto General Hospital has made this institution a national and international resource for education and patient care, and a leader in diabetes, transplantation, cardiology, surgical innovation, infectious diseases and genomic medicine.

Posted by dlife at 09:52 AM | Comments (0)

No 'Convincing Evidence' That Glitazones Work Better Than Older Diabetes Drugs

Glitazones in type 2 diabetes: an update DTB

April 9, 2008 (EurekAlert) - There is no convincing evidence that the newer class of diabetes drugs, known as glitazones, offer real advantages over other diabetes drugs, when used on their own, concludes the Drug and Therapeutics Bulletin (DTB).

The glitazones (pioglitazone and rosiglitazone), which are also used in combined double and triple therapy, now account for over half of the NHS spend on oral drugs for the regulation of blood sugar (glycaemic control).

New guidance on glitazones from the National institute for Health and Clinical Excellence (NICE) is expected next month.

An exhaustive trawl of the available evidence leads DTB to conclude that glitazones have a place in combined treatments with either metformin or a sulphonylurea people with type 2 diabetes who are unsuited to one or other of these older drugs.

But DTB makes it clear that there is “no convincing evidence” that when taken alone the glitazones produce greater health benefits than either of the other types of treatment.

“Evidence for their use in triple therapy is also weak, and they should be reserved for patients in whom insulin is contraindicated or is likely to be poorly tolerated,” says DTB.

The drugs can have significant side effects, although the regulators still feel that the benefits outweigh the risks.

Heart failure is more common when treatment is combined with insulin.

And in 2007 the European medicines regulator, the EMEA, warned that patients with angina who had had certain types of heart attack should not be given rosiglitazone, and the drug was not recommended for those with ischaemic heart, or peripheral arterial, diseases.

And the US drugs regulator, the FDA, has also advised that rosiglitazone may increase the risk of a heart attack.

Heart failure is more common when glitazone treatment is combined with insulin, and research indicates higher rates of oedema (swelling) in both sexes and bone fractures in women.

DTB concludes that pioglitazone is probably the safer option of the two glitazones, but should still not be used in anyone at high risk of heart failure.

Although pioglitazone is licensed for use with insulin treatment, DTB says that this combination carries the risk of weight gain, oedema and potentially heart failure.

Posted by dlife at 09:45 AM | Comments (0)

Once-Daily Basal Insulin Glargine vs. Thrice-Daily Prandial

March 27, 2008

Insulin glargine as good at controlling blood sugar as insulin lispro but simpler and more liked by patients

March 27, 2008 (EurekAlert) - The use of insulin glargine, (a single injection of daily insulin) is as effective at controlling blood sugar for people with diabetes as insulin lispro (which has to be injected up to three times a day), and is associated with increased satisfaction among users. These are the conclusions of authors of an Article published in this week’s edition of The Lancet.

The use of insulin glargine, (a single injection of daily insulin) is as effective at controlling blood sugar for people with diabetes as insulin lispro (which has to be injected up to three times a day), and is associated with increased satisfaction among users. These are the conclusions of authors of an Article published in this week’s edition of The Lancet.

Controlling blood sugar can help people with diabetes avoid the occurrence of microvascular events (eg, retinopathy) and, to a lesser extent, macrovascular complications. Blood sugar control is measured using the concentration of haemoglobin A1c in the blood, and concentrations less than 7% (optimally less than 6.5%) can substantially reduce the risk of these complications. The amount of haemoglobin A1c is directly related to the amount of sugar in the blood.

Professor Reinhard G Bretzel, Justus-Liebig-Universität Giessen, Germany, and colleagues did the APOLLO study, a 44-week trial of 418 patients with type 2 diabetes in 69 study sites across Europe and Australia. All patients had diabetes that was not adequately controlled by oral hypoglycaemic drugs, and were randomly assigned to either insulin glargine injected once daily at the same time every day (205 individuals), or to insulin lispro injected three times per day (210).

The investigators found that both groups achieved similar reductions in haemoglobin A1c, with the average decrease in the insulin glargine group -1.7% (from 8.7% to 7.0%); in the insulin lispro group the average decrease was -1.9% (from 8.7% to 6.8%).

The authors conclude: “A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A1c. We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro.”

Posted by dlife at 10:13 AM | Comments (0)

Protein Target for Diabetes Drug Regulates Blood Pressure

March 04, 2008

March 4, 2008 (EurekAlert) - University of Iowa researchers have identified a molecular pathway in blood vessels that controls blood pressure and vascular function and may help explain why certain drugs for type II diabetes also appear to lower patients' blood pressure. The study is published in the March 5 issue of Cell Metabolism.

A majority of patients with type II diabetes, which is associated with obesity and metabolic syndrome, also are at risk for serious cardiovascular problems, including atherosclerosis, heart attack, stroke and hypertension. Understanding the biological pathways that link cardiovascular and metabolic function could lead to better treatments for the millions of Americans affected by these conditions.

The focus of the UI study is a protein called peroxisome proliferator-activated receptor gamma (PPAR gamma), which plays a critical role in fat metabolism and insulin action, and appears to link metabolic disorders, like type II diabetes, with cardiovascular disease.

Drugs called thiazolidinediones (TDZs), which are used to treat type II diabetes, target and activate PPAR gamma. In addition to controlling blood sugar, these drugs also appear to lower blood pressure.

The UI team led by Curt Sigmund, Ph.D., professor of internal medicine and molecular physiology and biophysics in the UI Roy J. and Lucille A. Carver College of Medicine, and Carmen Halabi, a student in the UI Medical Scientist Training Program and the study's lead author, tested the idea that these two beneficial effects of TZDs are produced through two separate PPAR gamma pathways.

Working with mice, the team knocked out the function of PPAR gamma in vascular smooth muscle, which surrounds blood vessels. The mice developed high blood pressure and very severe vascular dysfunction, which resembled the vascular disorders often seen in patients with advanced type II diabetes.

"It appears that when PPAR gamma is activated it initiates a cascade of events that protect the blood vessel," Sigmund explained. "When we interfere with the PPAR gamma pathway, those protective mechanisms are eliminated and the blood vessel becomes dysfunctional."

Although TZDs have been used for many years to treat type II diabetes, they do have several serious side effects, including weight gain and water retention. A recent study also suggested that one TZD (rosiglitazone, which is sold as Avandia) might increase the incidence of fatal and non-fatal heart attacks in diabetes patients. Avandia now carries an FDA warning.

"These side effects really highlight the need to figure out ways to dissociate beneficial effects from dangerous side effects," Sigmund said. "By understanding the mechanisms that lead to those effects we may be able to enhance benefits and minimize dangers.

"When a drug is found to have serious side effects, people often think that the molecule the drug targets is no longer relevant," he added. "But that is not the case. We know from our study and from others that the molecule is still very relevant. We just need drugs with higher specificity."

Sigmund also noted that Halabi's combined training in medicine and bench science helped to focus the genetic study on an area with direct clinical relevance.

"This study is at the interface of her knowledge of clinical medicine and the basic science," he said.

PPAR gamma is a transcription factor and when it is activated, a cascade of signals is initiated, which controls gene expression -- some genes are turned on and others are turned off. In particular, inflammatory genes are turned off and antioxidant genes are turned on.

Having identified the PPAR gamma pathway, the next question for the researchers is which genes are being turned on or off to produce the antihypertensive effect" Identifying these genes may lead to more specific ways of treating hypertension and vascular disease in patients with diabetes.

Posted by dlife at 05:01 PM | Comments (1)

Women are Treated Less Frequently than Men with Statins, Aspirin and Beta- Blockers

March 4, 2008 (Newswise) — Women and men experience a similar prevalence of adverse drug reactions in the treatment of coronary artery disease; however, women are significantly less likely than their male counterparts to be treated with statins, aspirin, and beta-blockers according to a new study by researchers at Rush University Medical Center. The study is published in the March issue of the journal Gender Medicine.

“Developments in disease recognition and novel treatment strategies have led to a significant decline in overall cardiovascular death rate among men, but these dramatic improvements have not been observed in women,” said Dr. Jonathan R. Enriquez, lead author of the study and resident internal medicine physician at Rush. “This may be related to underutilization of medical therapies such as aspirin, ß-blockers, ACE inhibitors or statins.”

In association with Dr. Annabelle Volgman and the Rush Heart Center for Women, the study involved 304 consecutive patients with coronary artery disease at the outpatient cardiology clinic at Rush. A retrospective observational analysis was performed to determine the usage and adverse reactions reported from aspirin, ß-blockers, angiotensin-converting-enzyme (ACE) inhibitors or statins. Baseline clinical characteristics were also determined to identify the independent association of gender on usage of standard medical coronary artery disease treatments.

The study found that only 78.1 percent of women were treated with statins compared to 90.8 percent of men. After adjustment for clinical characteristics, men were also found to be six times more likely to receive aspirin and beta-blockers. No significant difference was noted between genders in the prevalence of adverse drug reactions.

“The physician’s perception of either anticipated adverse drug reactions or less severe disease may be influencing their decision to not prescribe these medications for women,” said Enriquez. “We encourage further studies to identify the cause of this disparity, so that care for women with coronary artery disease may be optimized.”

Coronary artery disease is the leading-cause of death among women in the United States and annually since 1984 the number of cardiovascular-related deaths in women has exceeded that of men. Women may not only suffer from decreased survival with coronary artery disease, but may also experience a worse quality of life than men.

“Given the findings of this study and other studies documenting the underutilization of current medical therapies in women, we must consider potential solutions to improve care of all patients during the outpatient visit,” said Enriquez.

At the Rush Heart Center for Women, women with heart problems are diagnosed and treated with great sensitivity and innovation by a team of cardiologists, nurse practitioners, nurses, nutritionists and cardiothoracic surgeons who are supported by the comprehensive resources of a world-class academic medical center. Women without overt heart disease are assessed and advised on how to prevent heart disease and stroke.

Rush University Medical Center is an academic medical center that encompasses the more than 600 staffed-bed hospital (including Rush Children’s Hospital), the Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, and one of the nation’s top-ranked nursing colleges. Rush University also offers graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness, neurological disorders and diseases associated with aging.

Posted by dlife at 10:39 AM | Comments (0)

Eucreas®, a Single-Tablet Combination of Galvus® and Metformin, Set for Launch in First EU Countries as New Treatment for Type 2 Diabetes

February 25, 2008

February 25, 2008 (Press Release) - European health authorities have approved Eucreas®, an oral tablet combining Galvus® (vildagliptin) and metformin, as a new treatment for patients with type 2 diabetes. Eucreas is the first single-tablet combination of a member of the new DPP-4 inhibitor class with metformin to be approved in the European Union.

The approval comes after Novartis proposed changes to the EU label recommending that liver monitoring should be conducted at the start of treatment, every three months for the first year, and periodically thereafter. The Eucreas approval closely follows European approval of the updated label for Galvus announced earlier this month.

The decision applies in all 27 countries of the EU as well as in Norway and Iceland, and both medicines will be available in the first European countries within the next few weeks.

Studies show that more than half of patients currently taking medication to manage their type 2 diabetes are still not reaching blood glucose goals[1]. Combination therapy usually becomes necessary due to progressive worsening of blood sugar control during the natural course of the disease[2].

In clinical studies, patients inadequately controlled on metformin, one of the most prescribed oral therapies for type 2 diabetes, were four times more likely to achieve blood sugar control by adding Galvus to their treatment compared to those who added a placebo (or sugar pill)[3]. Furthermore, Galvus when administered with metformin resulted in additional blood sugar reductions of 1.1% as measured by HbA1c[4], the gold standard measure of blood sugar control[5].

"The approval of Eucreas marks an important step forward in the management of type 2 diabetes, as it is the first single-tablet combination of a DPP-4 inhibitor with metformin for patients in Europe," said James Shannon, MD, Chief Medical Officer at Novartis Pharma AG. "The complementary actions of Galvus and metformin, which are the medicines combined in Eucreas, help to bring blood sugar levels under control without the side effects commonly associated with many widely-used type 2 diabetes medicines."

In clinical trials, the addition of Galvus to metformin provided robust blood sugar control without weight gain and with fewer cases of hypoglycemia (i.e. dangerously low blood sugar)[4], side effects associated with other therapies for type 2 diabetes such as sulfonylureas or thiazolidinediones.

Eucreas has been approved for use in type 2 diabetes patients who are inadequately controlled with metformin alone, or are being treated with Galvus and metformin as separate tablets. Eucreas is recommended for use twice-daily at a dose of either 50 mg vildagliptin/850 mg metformin or 50 mg vildagliptin/1000 mg metformin.

Eucreas combines two agents that work together to target both a dysfunction in the pancreatic islets and insulin resistance, two of the main factors contributing to type 2 diabetes. Galvus works through a novel mechanism of action that targets islet dysfunction and restores the body's natural ability to increase insulin and decrease glucagon - the two main hormones controlling blood sugar levels. Metformin works mainly by decreasing the production of sugar by the liver and increasing insulin sensitivity.

Type 2 diabetes is a progressive disease in which control of blood sugar deteriorates over time. If left untreated or not kept under control, it can lead to heart and kidney disease, blindness, and vascular or neurological problems[6].

References
[1] Saydah S, et al. Poor Control of Risk Factors for Vascular Disease Among Adults With Previously Diagnosed Diabetes. JAMA 2004: 291(3): 335-342.
[2] Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 281:2005-2012, 1999.
[3] Dejager S, et al. Achievement of Glycemic Targets with Vildagliptin. Presented at EASD 17-21 September 2007. (Abstract A-07-899).
[4] Bosi E, et al. Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients With Type 2 Diabetes Inadequately Controlled With Metformin. Diabetes Care. 2007; 30:890-895.
[5] American Diabetes Association. Standards of Medical Care in Diabetes - 2006. http://care.diabetesjournals.org/cgi/content/full/29/suppl_1/s4
[6] International Diabetes Federation Diabetes Atlas. Third edition 2006: http://www.eatlas.idf.org/

Posted by dlife at 10:47 AM | Comments (0)

Novo Nordisk Refocuses Its Activities Within Inhaled Insulin and Discontinues the Development of AERx®

January 14, 2008

January 14, 2008 (Press Release) - Based on a detailed analysis of the future prospects for inhaled insulin and a review of the medical and commercial potential of the AERx® iDMS inhaled insulin system (AERx®), Novo Nordisk has decided to refocus its inhaled insulin activities and discontinue all further development of AERx®. The decision to discontinue the development of AERx® is not due to safety concerns. The decision impacts the company's 2007 operating profit with a non-recurring cost of around DKK 1.3 billion.

"The AERx® system has been developed for delivering fast-acting insulin in connection with meals, and we have concluded that fast-acting inhaled insulin in the form it is known today is unlikely to offer significant clinical or convenience benefits over injections of modern insulin with pen devices such as Novo Nordisk's FlexPen®," says Lars Rebien Sørensen, president & CEO of Novo Nordisk. He continues: "In general, people with type 2 diabetes start insulin therapy with long-acting or premixed insulin, and experience shows that they want very simple, very convenient devices for administering their insulin. This requires a completely new approach to inhalation of insulin."

Against this background, Novo Nordisk will increase research and development activities targeted at inhalation systems for long-acting formulations of insulin and GLP-1. The activities will take place at two centres of excellence in Hayward, California, and Hillerød, Denmark.

The people with diabetes who are currently participating in phase 3 clinical trials with AERx® will be switched to the treatment alternative recommended by their doctors. Subject to local regulations, Novo Nordisk will fund medication and medical supervision for the planned duration of the trials.

"We regret the inconvenience caused by the termination of the trials and will do our utmost to support doctors and medical staff in ensuring as smooth a transition as possible for the affected patients," says Lars Rebien Sørensen.

Activities related to clinical development and manufacturing of AERx® devices and insulin strips will be discontinued. As a consequence of this decision, a significant number of employees at Novo Nordisk's site in Hayward, California, are expected to become redundant.

Financial implications
For 2007, a non-recurring cost of discontinuing all clinical development and manufacturing activities related to the AERx® system is expected to amount to around DKK 1.3 billion which will negatively impact operating profit in 2007. Around DKK 900 million relates to write-down and impairment of tangible and intangible assets, around DKK 300 million relates to the discontinuation of clinical trials and, finally, around DKK 100 million relates to other exit costs such as leasing and investment commitments. For 2007, the discontinuation will not impact the reported cash flow.

Novo Nordisk will provide financial results for 2007 and detailed financial guidance for 2008 in connection with the release of the full-year 2007 financial results on 31 January 2008.

However, at the current point in time, Novo Nordisk can reconfirm the sales growth guidance given in connection with the release of the financial results for the first nine months of 2007 on 31 October 2007. For 2007, sales growth measured in local currencies is now expected to be realised in the middle of the 11-14% range indicated as part of the release of the financial results for the first nine months of 2007. Furthermore, as the discontinuation primarily impacts R&D costs in 2007, Novo Nordisk now expects the R&D to sales ratio for 2007 to be slightly more than 20%.

For 2008, the discontinuation of further development of AERx® is expected to result in an R&D to sales ratio of around 17% including a non-recurring cost of around DKK 300 million related to severance payments and other costs.

Posted by dlifenews at 09:33 AM | Comments (0)

New Consumer Guides on Oral Diabetes Medications

December 17, 2007

December 17, 2007 (Newswise) — A pair of plain-language guides that outline the latest scientific evidence on the effectiveness and safety of oral medications for adults with type 2 diabetes are now available from HHS’ Agency for Healthcare Research and Quality.

AHRQ's analysis is the first to summarize evidence on the effectiveness and adverse events for all commonly used type 2 diabetes medications. As new classes of oral diabetes medications have become available, patients and clinicians have faced a growing list of treatment options and choices. The guides for consumers and clinicians are tools to help patients, their families, and health care providers make informed decisions about treating a condition that affects more than 15 million Americans.

The consumer-targeted guide, called Pills for Type 2 Diabetes: A Guide for Adults, includes information on:

· Types of diabetes pills commonly available for adults
· How well they work
· Possible side effects
· Medication costs

The clinician’s guide, called Comparing Oral Medications for Adults With Type 2 Diabetes, includes more detail on those topics and “confidence ratings” for evidence to support research conclusions.

Type 2 diabetes is an increasingly common chronic disease that occurs in people who have too much glucose in their blood either because their cells are resistant to insulin (a hormone that helps convert glucose into energy) or because their pancreas does not produce enough insulin. Excessive glucose levels can cause severe problems with the heart, eyes, kidneys and nerves. Obesity increases the risk of developing diabetes.

The diabetes guides are part of a series of informational products created by the Agency’s Effective Health Care program. Online and audio versions are available at http://effectivehealthcare.ahrq.gov/index.cfm. Free print versions can also be ordered.

Posted by dlifenews at 09:44 AM | Comments (0)

Insulin Regulates the Secretion of the Antiaging Hormome Klotho

November 27, 2007

November 27, 2007 (EurekAlert) - Dr. Carmela Abraham, a professor of biochemistry and medicine at Boston University School of Medicine (BUSM), reports this week in the Proceedings of the National Academy of Sciences new findings on Klotho, an anti-aging gene that is associated with life span extension in rodents and humans. Dr. Abraham’s interest in Klotho stems from her studies comparing the expression of genes in young and old brains.

Dr. Abraham and her colleagues observed that the levels of Klotho in the brain showed a striking decrease with aging. The association between Klotho and aging prompted Abraham’s group to investigate the regulation of Klotho further. These studies lead to the observation that secretion of Klotho is regulated by insulin.

The Klotho protein sits in the membrane of certain cells but is also found circulating in serum and cerebrospinal fluid, which indicates that it is secreted. The fact that Klotho is secreted suggested that enzymes that act like scissors must be involved in the liberation of Klotho from the cell membrane.
Dr. Ci-Di Chen, an assistant professor working in Dr. Abraham’s group, then sought to identify the enzymes responsible for Klotho release and also investigated other factors that may affect the release of active Klotho.

To their surprise, they found that insulin, a hormone usually associated with diabetes, increases significantly the levels of secreted Klotho. The reason this finding is important is because excess insulin has been previously implicated in a biochemical pathway that is associated with a decreased life span and elevated oxidative stress.

In addition, this observation provides a potentially pivotal link between Klotho and sugar metabolism, and raises an intriguing relationship between Klotho and type II diabetes, commonly known as late onset diabetes. The authors are proposing a novel mechanism of action for Klotho whereby insulin increases Klotho secretion, i.e., activity, and in turn, the secreted Klotho inhibits insulin’s actions in the cell, which are known to be detrimental when insulin is in excess.

Sonia Podvin, Earl Gillespie and Dr. Susan Leeman, all from Boston University School of Medicine, also participated in the study.

Following these findings, the Abraham laboratory is now studying various ways to increase the level of Klotho to those levels found in young individuals. “The findings reported here may lead to new research designed to regulate the aging process, in other words, compounds that would increase Klotho could become the next “fountain of youth,” said Abraham.

Posted by dlifenews at 10:44 AM | Comments (0)

GlaxoSmithKline Revises US Labeling for Avandia®

November 14, 2007

November 14, 2007 (Press Release) - GlaxoSmithKline announced today that it is implementing changes to the US product label for Avandia® (rosiglitazone maleate), based on an extensive and thorough review by the FDA of myocardial ischemia data on Avandia, the most widely studied oral anti-diabetic medicine available.

The existing boxed warning has been revised to add the FDA’s conclusion that, while an FDA meta-analysis of short-term studies – mostly against placebo - showed an association between Avandia and an increase in myocardial ischemic events, that risk was not confirmed or excluded in three long-term clinical trials comparing Avandia against both placebo and other oral anti-diabetes medicines. The box will state that the available data on the risk of myocardial ischemia are inconclusive.

The FDA has also concluded there is insufficient information available to determine whether any oral anti-diabetic medicine reduces cardiovascular risk. The FDA has directed that the sentence - “There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Avandia or any other oral antidiabetic drugs” - will be added as a warning on the labels of all oral anti-diabetic medicines.

The Avandia label also has been updated to add that Avandia is not recommended - though not contraindicated - for use with patients who are taking insulin or nitrates. The label summarizes the data on myocardial ischemia to help doctors continue to evaluate which patients could benefit from taking Avandia, and those for whom alternative treatment should be considered.

The changes are now included in labeling for Avandia, and will be incorporated into future revised labeling for all approved rosiglitazone-containing products, including Avandamet (rosiglitazone maleate and metformin hydrochloride), and Avandaryl (rosiglitazone maleate and glimepiride). GSK is also preparing a Medication Guide to help educate patients about potential benefits and risks and to provide other information on Avandia.

“Avandia remains a valuable medicine for most patients with type 2 diabetes, and when used according to the labeling, has a well described and appropriate safety and effectiveness profile,” said Dr. Ronald Krall, GSK Chief Medical Officer. “Given the severity of this disease and the importance of Avandia in helping patients manage their diabetes, we will continue to work with the FDA to conduct more studies about the safety and benefits of our medicine.”

As previously stated by GSK, two long-term trials in diabetic patients comparing Avandia to other oral anti-diabetic medicines show no increased risk for cardiovascular events compared to other commonly used medications, other than the well-known risk of congestive heart failure with TZDs. One trial – ADOPT - shows no increased myocardial ischemic risk compared to metformin or sulfonylurea. The interim results of a second long-term trial – RECORD - also show no increased risk of major cardiovascular events (death, heart attack and stroke) between Avandia and other medications; however, firm conclusions cannot be drawn because the trial has not yet been completed. The updated label includes data from ADOPT and RECORD plus a third long-term trial in pre-diabetic patients (DREAM). The combined analysis of these three studies show there was no increased risk of Avandia over comparatorswith regard to myocardial infarction, mortality, or other non-heart failure cardiovascular events.

GSK believes data from ongoing and future clinical trials will provide additional scientific support for both the benefit and safety of Avandia. GSK has agreed to work with the FDA to plan and carry out a clinical trial to further investigate the cardiovascular effects of Avandia.

Avandiahas been prescribed to more than seven million people over the last seven years to help them control their blood sugar levels. Importantly, Avandia has been shown to control blood sugar for longer than the most commonly used oral anti-diabetic medicines – up to five years. Long-term glycemic control is important to help prevent the serious complications of diabetes, especially microvascular complications leading to blindness, amputation and kidney failure. Avandia is an important treatment option for physicians, since two-thirds of diabetic patients suffer with uncontrolled disease and many require two or three medicines to maintain their blood sugar.

GlaxoSmithKline — one of the world’s leading research-based pharmaceutical and healthcare companies — is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com.

Posted by dlifenews at 03:26 PM | Comments (0)

Pfizer Reports Third-Quarter 2007 Results: Announces Company Will Exit Exubera Inhaled Insulin Business

October 18, 2007

October 18, 2007 (BUSINESS WIRE) -- Pfizer: Pfizer Inc posted third-quarter 2007 revenues of $12.0 billion, a 2% decline from the same period last year. The Company’s reported net income was $761 million in the third quarter of 2007, a decrease of 77% from the same period last year, primarily reflecting pre-tax charges of $2.8 billion related to the decision to exit Exubera, our inhaled insulin product to treat diabetes. Adjusted income(1) for the third quarter of 2007 increased 1% to $4.0 billion compared to the third quarter of 2006.

“We are encouraged by our operating results in the third quarter, and we remain on track to achieve our full-year 2007 revenues and adjusted diluted EPS(1) goals. Meanwhile, we made an important decision regarding Exubera, a product for which we initially had high expectations,” said Jeff Kindler, Chairman and Chief Executive Officer. “Despite our best efforts, Exubera has failed to gain the acceptance of patients and physicians. We have therefore concluded that further investment in this product is unwarranted.”

“We will work with physicians to transition Exubera patients to other treatment options in the next three months. We remain committed to investing significant resources in the development of new and innovative medicines to manage diabetes, including monitoring inhalation technologies and other innovative delivery systems for insulin and other medicines.”

Frank D’Amelio, Chief Financial Officer, added, “The Exubera pre-tax charges of $2.8 billion related primarily to the write-off of assets associated with this product, as well as the accrual of other exit costs. More specifically, these charges are comprised of approximately $1.1 billion of intangible assets, $661 million of inventory, $454 million of fixed assets and $584 million of other exit costs.”

Commenting on the financial performance in the just-ended quarter, Mr. Kindler said, “We are achieving our operational goals in the face of major revenue losses due to patent expirations in the U.S. Most of our new products(3) along with the favorable impact of foreign exchange are contributing significantly toward offsetting these losses as evidenced by our year-to-date results.”

Mr. Kindler continued, “While optimizing revenues from our in-line products(2) and generating strong growth from our new products(3), we remain focused on driving a series of fundamental changes in the Company to improve our performance and achieve a lower, more flexible cost base. We are making substantial progress on these priorities. For example, our reduction in adjusted selling, informational and administrative expenses(1) this year is expected to exceed our previous forecast on a constant currency basis(8).”

“However, we need to deliver better results, continue to make tough decisions about allocating our capital wisely, and bring more new products to the market as quickly as possible. Doing all of this will put Pfizer on the right course and build value for our shareholders.”

Read the rest of the Pfizer Third Quarter Earnings Release Here

Posted by dlifenews at 12:17 PM | Comments (0)

FDA Approves Supplemental New Drug Applications for JANUVIA™ (sitagliptin)

October 17, 2007

Oct. 17, 2007 (Merck) – Merck & Co. Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved expanded labeling for JANUVIA™ (sitagliptin), the only DPP-4 inhibitor available in the United States for the treatment of type 2 diabetes. JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUVIA has not been studied in combination with insulin. The new regimens with JANUVIA described in the updated labeling include, as an adjunct to diet and exercise, initial therapy in combination with metformin; add-on therapy to a sulfonylurea (glimepiride) when the single agent alone does not provide adequate glycemic control; and, add-on therapy to the combination of a sulfonylurea (glimepiride) and metformin when dual therapy does not provide adequate glycemic control.

New data contained in three studies support the efficacy and safety of JANUVIA. Initial therapy with the combination of JANUVIA and metformin provided substantial A1C reductions. JANUVIA demonstrated similar efficacy to a sulfonylurea (glipizide) in patients inadequately controlled on metformin. JANUVIA also provided significant placebo-adjusted A1C reductions in patients being treated with a sulfonylurea (glimepiride), with or without metformin.

The expanded labeling for JANUVIA was also updated, within Warnings and Precautions, to include post-marketing reports of hypersensitivity reactions in patients treated with JANUVIA. These reactions include anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The expanded labeling also includes a contraindication for patients with history of a serious hypersensitivityreaction to sitagliptin, including anaphylaxis and angioedema.

Since its initial approval in October 2006, over two million prescriptions have been written for JANUVIA. In controlled clinical studies as both monotherapy and combination therapy with metformin or pioglitazone, the overall incidence of adverse reactions, hypoglycemia, and discontinuation of therapy due to clinical adverse reactions with JANUVIA were similar to placebo. In these clinical studies, the most common adverse reactions reported with JANUVIA (greater than or equal to 5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection and headache. In clinical trials in combination with a sulfonylurea (glimepiride), with or without metformin, JANUVIA demonstrated an overall incidence of adverse reactions higher than that seen with placebo, in part related to a higher
incidence of hypoglycemia.

Initial therapy with the combination of JANUVIA and metformin provides significantly greater A1C reductions with a similar GI tolerability profile compared to metformin alone

JANUVIA as initial therapy in combination with metformin is supported by a randomized, double-blind, placebo-controlled factorial study in 1,091 patients with type 2 diabetes who experienced inadequate glycemic control with diet and exercise alone. In this study, the mean reduction of A1C relative to placebo at 24 weeks was 2.1 percent with initial therapy combining JANUVIA 100 mg daily and metformin 2000 mg dailyi (n=178) from a mean baseline A1C of 8.8 percent (p <0.001). The mean placebo-adjusted A1C reductions in the other arms of the study were 1.6 percent with JANUVIA 100 mg daily and metformin 1000 mg dailyii (n=183); 1.3 percent with metformin 2000 mg dailyiii (n=177); 1.0 percent with metformin 1000 mgiv daily (n=178); and 0.8 percent with JANUVIA (n=175), (p<0.001 for all treatment groups versus placebo).

At 24 weeks, 66 percent of patients treated with the initial combination of JANUVIA 100 mg daily and metformin 2000 mg daily achieved the American Diabetes Association's (ADA) goal A1C level of <7 percent vs. 38 percent of patients treated with metformin 2000 mg daily alone. In the other arms of the study, 43 percent of patients treated with JANUVIA 100 mg daily and metformin 1000 mg daily, 23 percent of patients treated with metformin 1000 mg daily, and 20 percent of patients treated with JANUVIA achieved the ADA goal A1C level of <7 percent.

This study also included an open label cohort of an additional 117 patients with severely elevated baseline A1C (mean: 11.2 percent). These patients experienced a significant mean A1C reduction from baseline of 2.9 percent at 24 weeks with initial therapy combining JANUVIA 100 mg daily and metformin 2000 mg daily.

This study also compared the efficacy of JANUVIA to two common doses of metformin in a subset of patients not on any anti-hyperglycemic agent at study entry. In this patient population, patients treated with JANUVIA experienced a mean A1C reduction from baseline of 1.1 percent compared to 1.1 percent in patients treated with metformin 1000 mg daily and 1.2 percent in patients treated with metformin 2000 mg daily.

“The substantial A1C reductions that are seen when JANUVIA is used in combination with metformin as first-line therapy in patients with type 2 diabetes are meaningful to me as a clinician. The data show that this approach helped many patients achieve their A1C goal and the rate of gastrointestinal side effects was similar to that seen with metformin alone,” said Barry J. Goldstein, M.D., Ph.D., professor of medicine, Biochemistry and Molecular Pharmacology; director, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College, Philadelphia, PA.

Initial combination therapy or maintenance of combination therapy may not be appropriate for all patients. These management options are left to the discretion of the physician.

In the factorial study, initial therapy with JANUVIA and metformin was not associated with an increased risk of gastrointestinal adverse reactions beyond those commonly seen with metformin alone. In a pooled analysis of four other placebo-controlled clinical studies with JANUVIA, not including initial therapy with JANUVIA and metformin, the incidence of selected gastrointestinal adverse reactions in patients treated with JANUVIA was abdominal pain (2.3 percent JANUVIA; 2.1 percent placebo); nausea (1.4 percent JANUVIA; 0.6 percent placebo); and diarrhea (3.0 percent JANUVIA; 2.3 percent placebo).

The incidence of hypoglycemia was similar across treatment groups (0.6 percent in patients on placebo, 0.6 percent in patients given JANUVIA alone, 0.8 percent in patients given metformin alone, and 1.6 percent in patients given JANUVIA in combination with metformin).

The most common adverse reactions reported with JANUVIA and metformin as initial therapy (greater than or equal to 5 percent) compared to metformin alone were upper respiratory infection (6.2 percent vs. 5.2 percent) and headache (5.9 percent vs. 3.8 percent).

JANUVIA demonstrated similar efficacy compared to a sulfonylurea (glipizide) with significantly less hypoglycemia, and patients treated with JANUVIA experienced mean weight loss from baseline of 1.5 kg

The efficacy of JANUVIA was also evaluated in a 52-week, double-blind, glipizidecontrolled
noninferiority trial predominantly in patients with mildly to moderately elevated A1C levels (mean baseline A1C 7.5 percent). Patients were treated with either JANUVIA 100 mg daily or glipizide up to 20 mg daily (mean daily dose 10 mg daily). This study showed that JANUVIA achieved the pre-specified bounds for noninferiority vs. a sulfonylurea (glipizide).

After one year, the mean A1C reduction from baseline was 0.5 percent for JANUVIA and 0.6 percent for glipizide in the intent-to-treat patient populationv and 0.7 percent for JANUVIA and 0.7 percent for glipizide in the per protocol analysisvi, confirming the similar efficacy of JANUVIA compared to glipizide.

Patients treated with JANUVIA experienced significant weight loss (mean -1.5 kg) from baseline at 52 weeks, while patients treated with glipizide experienced significant weight gain (mean +1.1 kg) from baseline at 52 weeks. Additionally, patients treated with JANUVIA experienced a lower incidence of hypoglycemia than patients treated with glipizide (4.9 percent vs. 32.0 percent, respectively, p<0.001). The noninferiority of JANUVIA to glipizide may be limited to patients with A1C levels comparable to those included in this study (over 70 percent of patients had a baseline A1C <8 percent and over 90 percent had a baseline A1C <9 percent).

JANUVIA provides significant additional A1C reductions, even in patients on triple therapy

The new regimens for adding JANUVIA to a sulfonylurea (glimepiride) with or without metformin are supported by a 24-week, randomized, double-blind, placebo-controlled study examining the efficacy and safety of JANUVIA in 441 patients with type 2 diabetes and inadequate glycemic control (A1C 7.5 percent to 10.5 percent) on a sulfonylurea (glimepiride) and metformin or on a sulfonylurea (glimepiride) alone. In this study, JANUVIA demonstrated a significant mean difference from placebo in A1C of -0.9 percent when added to patients on glimepiride and metformin and -0.6 percent when added to patients on glimepiride alone (p<0.001 for both comparisons versus placebo).

In this study, the overall incidence of clinical adverse reactions with JANUVIA was higher than that seen with placebo, in part related to a higher incidence of hypoglycemia with JANUVIA compared to placebo (12.2 percent vs. 1.8 percent, respectively). The higher rate of hypoglycemia is commonly seen when antihyperglycemic agents are used in combination with sulfonylurea agents. After 24 weeks, patients treated with JANUVIA had a mean increase in body weight of 1.1 kg versus placebo (+0.8 kg vs. -0.4 kg).

As is typical with other anti-hyperglycemic agents used in combination with a sulfonylurea, when JANUVIA is used in combination with a sulfonylurea, a class of medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea may be required to reduce the risk of hypoglycemia.

Dosing of JANUVIA

The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl ≥50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in end-stage renal disease (ESRD) patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl ≥30 to <50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl <30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.

Selected cautionary information for JANUVIA

Because JANUVIA is renally eliminated, and to achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, a dosage adjustment is recommended in patients with moderate renal insufficiency and in patients with severe renal insufficiency or with ESRD requiring hemodialysis or peritoneal dialysis. Safety and effectiveness of JANUVIA in pediatric patients have not been established. There are no adequate and well-controlled studies in pregnant women. JANUVIA should be used during pregnancy only if clearly needed. It is not known whether sitagliptin is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when JANUVIA is administered to a nursing woman. There have been post-marketing reports of hypersensitivity reactions in patients treated with JANUVIA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.

Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first three months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event and institute alternative treatment for diabetes.

Expanding clinical development program for sitagliptin family

Merck’s clinical development program for sitagliptin is robust and continues to expand with 49 studies completed or underway. Five additional studies are set to begin this year. It is estimated that there have been more than 9,400 patients in the Company’s clinical studies, with about 6,000 of these patients being treated with sitagliptin. Additionally, about 2,300 patients have been treated with sitagliptin for more than a year and, of these, approximately 400 patients have been treated for at least two years.

Posted by dlifenews at 04:30 PM | Comments (0)

FDA Announces Initiative to Bolster Generic Drug Program

October 04, 2007

Effort will streamline generic drug approval process; provide more options for consumers, health professionals

October 4, 2007 (FDA) - The U.S. Food and Drug Administration today outlined a program aimed at increasing the number and variety of generic drug products available to consumers and health care providers. Generic drugs generally cost less than their brand-name counterparts and competition among generics has been a key factor in lowering drug prices. The Generic Initiative for Value and Efficiency, or GIVE, will help the FDA modernize and streamline its generic drug approval process.

The agency approved or tentatively approved a record of 682 generic drugs products in fiscal year 2007, over 30 percent more than the previous year.

“To keep pace with the increasing number of generic drug applications, FDA will implement some changes to the generic drug approval process,” said Gary Buehler, director of FDA’s Office of Generic Drugs. “The GIVE plan outlines ways to maximize the use of our resources so that FDA can review and approve even more high quality generic drugs during the upcoming fiscal year than it did in 2007.”

As part of the GIVE efforts, FDA is revising the review order for certain drug applications. For example, first generic products, for which there are no blocking patents or exclusivity protections on the reference listed drug, are identified at the time of submission for expedited review. This will mean that these products, for which there are currently no generic products on the market, may reach the consumer much faster.

FDA now has about 215 full-time staff working on the review of generic drug applications. Under GIVE, FDA will hire and train new generic drug reviewers and focus on enhanced use of electronic programs for handling drug submissions and internal documents. When possible, resources from other FDA departments will be engaged in the effort. As well, FDA will increase its communications with generic drug manufacturers and provide training on proper application submission to the industry in meetings and Webcasts.

Generic drugs undergo a rigorous scientific review to ensure that they are of high quality, safe, and effective. Generic drug manufacturers must demonstrate that a generic drug has the same dosage form, strength, route of administration, and conditions of use as the approved brand-name product. Generic drug manufacturers also must demonstrate bioequivalence, meaning they show that the drug delivers the same amount of its active ingredient in the same amount of time as the brand-name counterpart. Bioequivalence is a critical requirement for concluding that the original and generic drugs will produce the same therapeutic results.

Posted by dlifenews at 04:57 PM | Comments (1)

One Year Study of Exenatide Treatment Showed Improved Beta-Cell Function

September 21, 2007

-- When compared to insulin glargine, exenatide offered added benefits of
weight loss and improved beta-cell function when used with metformin --

September 21, 2007 (PRNewswire-FirstCall) – Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced study results comparing treatment of exenatide injection with insulin glargine on beta-cell function, glycemic control and weight in people with type 2 diabetes. Study findings showed one year of exenatide therapy, as compared to insulin glargine, markedly improved different indices of beta-cell function, along with similar glycemic improvement. In addition, patients treated with exenatide lost weight, whereas patients treated with glargine gained weight. These findings were presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Amsterdam, The Netherlands(1).

In this randomized study, 69 people with type 2 diabetes who were treated with exenatide (5 mcg BID for 4 weeks and 10 mcg BID to 20 mcg TID (20 mcg TID is a currently unapproved dosage of the marketed formulation of exenatide, BYETTA(R) (exenatide) injection) for the remainder of the year) or insulin glargine (both with metformin) were compared on measures of beta-cell function, blood sugar control and weight change after one year (52-weeks) of treatment.

In this study, people with type 2 diabetes who used exenatide for one year, compared to those treated with insulin glargine, showed significant improvements in beta-cell function as measured by arginine and glucose induced C-peptide (a peptide associated with insulin production) secretion during a glucose clamp procedure (a technique used to assess insulin secretion)(2,3). Specifically, C-peptide secretion in response to arginine administration (which produces maximal beta-cell stimulation) was 146 percent greater after one year of treatment with exenatide when compared to insulin glargine (mean ratio relative to baseline for exenatide and insulin glargine + or -SEM: 3.19 + or - 0.24 vs. 1.31 + or - 0.07, respectively, p<0.0001). First phase glucose induced C-peptide secretion was 52 percent greater after one year of exenatide compared to insulin glargine therapy (mean ratio relative to baseline + or -SEM: 1.75 + or - 0.10 vs. 1.16 + or - 0.06, respectively, p<0.0001). Second phase C-peptide secretion increased 185 percent more with exenatide (mean ratio relative to baseline + or -SEM: 3.05 + or - 0.22) versus insulin glargine (1.08 + or - 0.05, p<0.0001).

The average HbA1c of randomized patients at the start of the trial was 7.5 + or - 0.1 percent. Treatment with exenatide resulted in blood sugar control (as measured by reductions in HbA1c) comparable to treatment with insulin glargine (-0.8 + or - 0.1 percent and -0.7 + or - 0.2 percent, respectively, a difference between groups that was not statistically significant).

On average, exenatide treatment also resulted in a reduction in body weight. At the start of the study, randomized patients had a mean weight of 91.4 + or - 1.6 kg (201.6 + or - 3.5 lb). Patients on exenatide lost an average of 3.6 + or - 0.6 kg (7.8 + or - 1.4 lb), while those receiving insulin glargine gained an average of 1.0 + or - 0.8 kg (2.2 + or - 1.8 lb). The total difference in weight between the exenatide and insulin glargine groups was 4.6 kg (10.0 lb).

"Previous exenatide studies have shown comparable glycemic improvements when compared to insulin glargine, as well as improved beta-cell function that has only been associated with exenatide treatment," said Michaela Diamant, M.D., Ph.D., Associate Professor of Endocrinology, Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands, and an author of the study. "This study lends further support to past findings and showed that adding exenatide significantly improved beta-cell function as measured by both glucose and arginine induced insulin secretion."

The side effects associated with exenatide treatment were consistent with those seen in previous studies. In clinical trials, the most common side effect is nausea, most of which is mild to moderate, affecting approximately half of patients and usually decreasing over time. Exenatide-treated patients had a lower incidence of hypoglycemia compared to insulin glargine-treated patients (8.3 percent vs. 24.2 percent, respectively).

Posted by dlifenews at 02:32 PM | Comments (0)

Discovery May Pave the Way for a New Class of Diabetes Drugs

September 04, 2007

September 4, 2007 (Newswise) — A multidisciplinary team led by researchers at the University of California, San Diego has determined the structure of a protein found in cells that shows potential as a target for the development of new drugs to treat diabetes.

The study, published September 4 in the journal Proceedings of the National Academy of Sciences, described the structure of a protein—MitoNEET—that was previously identified as a site where diabetes drugs could operate. The discovery of the protein’s three-dimensional structure makes it possible to design small molecules that interact with it and modify its function. The researchers say that MitoNEET has a novel three-dimensional structure that makes it a particularly interesting candidate for the design of innovative compounds that can bind to it.

“This is the first time that a protein like this has ever been found,” said Patricia Jennings, a professor in UCSD’s department of Chemistry and Biochemistry who led the study along with Mark Paddock, a project scientist in UCSD’s Physics department. “It is a brand new structure, a unique beast, which makes it an exciting target for structure-based drug design. We are grateful about the highly collaborative spirit of the UCSD community that brought such diverse expertise and helped us tackle such a complex project.”

“Our work may provide a basis for the design of newer diabetes drugs that have potentially greater specificity and fewer side effects than existing ones,” added Paddock.

Following the initial work of co-authors Sandra Wiley, Anne Murphy and Jack Dixon at UCSD’s School of Medicine, and in collaboration with Herbert Axelrod and Aina Cohen at the Stanford Synchrotron Radiation Laboratory and Rachel Nechushtai at the Hebrew University of Jerusalem, also co-authors on the paper, the team determined that mitoNEET is an iron-sulfur protein. Iron-sulfur proteins have a variety of functions, including electron transfer, which is critical to cell metabolism, and the storage and transport of iron. In its free state, iron is highly toxic to cells and can lead to oxidative stress—the accumulation of reactive compounds that can damage the cell.

MitoNEET’s iron-sulfur cluster is loosely bound, a property that may be linked to one of its functions. When mitoNEET binds the type 2 diabetes drug Actos®, the iron-sulfur cluster becomes more stable. This drug was thought to work through an entirely different mechanism involving a different protein. However, the finding by Jerry Colca, presently at Metabolic Solutions Development Company in Kalamazoo, Michigan, that the thiazolidinediones—the class of diabetes drugs of which Actos® is a member—bind to mitoNEET indicated a possible mechanism involving mitoNEET. Colca’s finding inspired the UCSD-led study, which suggests that Actos® and similar drugs may protect cells from the damaging effects of free iron by keeping the iron-sulfur cluster attached to mitoNEET.

From mitoNEET’s structure, location and properties, it could also play a role as a sensor of oxidative stress in the cell. Oxidative stress is a problem in many diseases including diabetes. MitoNEET is confined to the mitochondria—structures within cells that convert nutrients into energy—where reactive compounds accumulate as nutrients are metabolized. MitoNEET’s structure would allow it to transfer electrons to and from, and therefore detect, these compounds.

“MitoNEET may be an example of an ever increasing group of proteins found to have more than one function. I think we are at the beginning of what is sure to be an interesting and biologically important puzzle.” said Paddock.

“It is intriguing to see these different pieces coming together,” explained Jennings. “There is growing evidence that mitochondrial dysfunction and compromised oxidative capacity is a problem in diabetes. MitoNEET has iron-sulfur clusters that can transfer electrons, and it binds insulin-sensitizing drugs. Now that we know the structure and physical properties of the protein we can use this knowledge for drug studies and studies of biological function.”

The team plans to use the new structural information for designing more sophisticated experiments to test function and structure-based drug design to create drugs that interact better with mitoNEET. Collaborative experiments are currently underway with Colca’s group at Metabolic Solutions Development Company.

“This work is a great example of the possible synergies of a multidisciplinary and multinational effort,” said Paddock. “Instrumental in these results were the combined efforts of the US and Israeli teams.”

Other UCSD co-authors of the paper were Edward Abresch in Physics and Melinda Roy and Dominique Capraro in Chemistry and Biochemistry.

The study was supported by the National Institutes of Health, the Department of Energy and the Zevi Hermann Shapira Foundation.

Posted by dlifenews at 02:12 PM | Comments (0)

Common Rheumatoid Arthritis Treatment Shows Potential For Diabetes Prevention

July 12, 2007

July 12, 2007 (Science Daily) — Far fewer rheumatoid arthritis patients treated with the drug hydroxychloroquine (HCQ) went on to develop diabetes compared to those who never took the drug, according to a 20-plus-year University of Pittsburgh School of Medicine-led study reported today in the Journal of the American Medical Association. In addition, those using HCQ who did develop diabetes were less likely to take medications to manage their disease after diagnosis.

The multi-center observational study of 4,905 adults with rheumatoid arthritis (RA) found that relative risk progressively declined by as much as 77 percent after four years of treatment with HCQ, a common antimalarial medication that also is used for rheumatoid arthritis and other autoimmune disorders.

Additional participating centers in the study are Stanford University, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), one of the National Institutes of Health (NIH) and the University of Cincinnati. Co-investigators at Stanford have directed the project database since its inception with support from the NIH.

"This reduction in risk persisted even after adjusting for other diabetes risk factors among these patients, such as body-mass index, degree of disability and use of corticosteroids," said rheumatologist Mary Chester M. Wasko, M.D., M.Sc., associate professor of medicine, University of Pittsburgh School of Medicine. Because people with RA tend to be less active and take corticosteroids that can cause weight gain, they are often considered to be at higher risk for developing diabetes, a disease in which blood sugar levels become abnormally high because of the body's inability to use or produce the hormone insulin.

"Another interesting finding was that the rheumatoid arthritis patients who developed diabetes were less likely to need blood sugar-lowering medication to manage their disease," said Dr. Wasko, whose clinical research has focused on long-term health improvement in patients with RA. "However, it is most exciting to consider that this drug might be appropriate for people with pre-diabetes as a preventive therapy -- much in the same way as a daily baby aspirin is suggested for people at high risk for heart disease."
Nationally, diabetes is the fifth leading cause of death, according to the American Diabetes Association. Many people first become aware of the disease when confronted with one of its life-threatening complications such as heart disease, blindness, high blood pressure, stroke, kidney disease or circulatory problems that can lead to amputation.

Results show that HCQ's association with reduction in diabetes risk is comparable or superior to that of a number of other drugs studied in clinical trials for diabetes prevention and treatment, including rosiglitazone, hormones, metformin, acarbose and ramipril. And recent questions have arisen concerning rosiglitazone, marketed as Avandia, and a reported increased risk of heart attack.

Although HCQ is not without side effects -- nausea, headache and dizziness, for example -- the drug has a long history of being generally safe and well-tolerated. In addition, Dr. Wasko and her colleagues observed no apparent negative interactions between HCQ and other drugs commonly used by RA patients, such as methotrexate and prednisone. An important limitation of the study, however, is that investigators used self-report information from patients collected in follow-up twice yearly that did not include confirmation by laboratory tests.

Other studies of the blood sugar-lowering effects of HCQ have shown minimal use for the drug as a treatment for people with established diabetes, Dr. Wasko continued, stressing the treatment's real promise may be prevention.

"HCQ already has a role in long-term treatment for RA, potentially moderating lipids and having a weak anti-clotting effect. But, optimistically speaking, endocrinologists can identify people who are at high risk for diabetes, due to obesity, family history, lipid profile or other characteristics. HCQ may also have a role in delaying onset of diabetes," Dr. Wasko said. "More research is needed to verify our findings in people with RA, and also to determine how this medicine works. But my ultimate hope is that this relatively inexpensive, safe drug will be studied as a way to reduce diabetes risk for people who do not have RA."

In addition to Dr. Wasko, study authors are Helen B. Hubert, M.P.H., Ph.D., James F. Fries, M.D., and Vijaya Bharathi Lingala, Ph.D., all of Stanford University Medical Center; Jennifer R. Elliott, M.D., University of Pittsburgh School of Medicine; Michael E. Luggen, M.D., University of Cincinnati; and Michael M. Ward, M.D., M.P.H., Intramural Research Program, NIAMS. The study was conducted with support from the Arthritis Foundation of Western Pennsylvania, NIAMS and the Intramural Research Program, NIAMS.

Financial disclosure: Dr. Wasko is a consultant to Centocor in cardiovascular outcomes in ongoing rheumatoid arthritis clinical trials and has been a co-investigator in a Merck-sponsored study of blood clot markers in rheumatoid arthritis and osteoarthritis. She also has received payment as site principal investigator for clinical trials for rheumatoid arthritis drugs sponsored by Sanofi-Aventis (ending in 2002), Centocor, Roche, Novartis and Human Genome Sciences. Hydroxychloroquine, marketed as Plaquenil ® is manufactured by Sanofi-Aventis. In its generic form, the drug has multiple manufacturers.

Note: This story has been adapted from a news release issued by University of Pittsburgh Schools of the Health Sciences.

Posted by dlifenews at 10:46 AM | Comments (0)

Selenium Supplements Linked with Increased Risk for Diabetes in 8-Year Study

July 10, 2007

July 10, 2007 (Eurekalert )-- A new analysis of data from a large national study found that people who took a 200 microgram selenium supplement each day for almost eight years had an increased risk of developing type 2 diabetes than those who took a placebo or dummy pill.

The data came from the Nutritional Prevention of Cancer Trial (NPC), a large randomized, multi-center, clinical trial from the eastern United States, designed to evaluate whether selenium supplements prevent skin cancer. In the study being published, researchers selected 1,202 participants who did not have diabetes when they were enrolled in the NPC Trial. Half received a 200 microgram selenium supplement and half received a placebo pill for an average of 7.7 years.

Saverio Stranges, MD, PhD, lead author of the study, says that the findings from this study suggest that selenium supplements do not prevent diabetes and that they might be harmful. “At this time, the evidence that people should take selenium supplements is extremely limited. We have observed an increased risk for diabetes over the long term in the group of participants who took selenium supplements.”

Dr. Stranges is currently working at Warwick Medical School, UK, but previously worked at the State University of New York at Buffalo. Other authors of the article include Mary E. Reid, PhD, and James R. Marshall, PhD, researchers at the Roswell Park Cancer Institute in Buffalo.

Selenium is a naturally occurring trace mineral present in soil and foods. The body need selenium in minute amounts to aid in metabolism. Selenium supplements are widely promoted on the Internet for conditions ranging from cold sores and shingles to arthritis and multiple sclerosis. They are sold to prevent aging, enhance fertility, prevent cancer and get rid of toxic minerals such as mercury, lead and cadmium.

Selenium supplements have shown some promise in preventing prostate cancer. Because of selenium’s antioxidant activities, some scientists feel it might be effective against diabetes.

In the current study, 58 out of 600 participants in the selenium group and 39 out of 602 participants in the placebo group developed type 2 diabetes. After 7.7 years of follow-up, the relative risk rate was approximately 50 percent higher among those randomly selected for the selenium group than among those randomly placed in the placebo group.

The results consistently showed higher risks of disease among participants receiving selenium across subgroups of baseline age, gender, and smoking status. However, the selenium supplements had no impact on the most overweight participants. The risk of developing diabetes tended to be higher in people who had higher blood selenium levels at the start of the study.

Dr. Stranges said, “No single study can provide the answer to a scientific question, but at this time, selenium supplementation does not appear to prevent type 2 diabetes, and it may increase risk of the disease. However, our understanding of the mechanisms whereby selenium would increase risk of diabetes is very limited at this time and this issue needs to be further explored. Nevertheless, I would not advise patients to take selenium supplements greater than those in multiple vitamins.”

About 60 percent of Americans take multivitamin pills, many of which contain between 33 and 200 micrograms of selenium, in addition to the selenium taken in from food and the air. The RDA (recommended dietary allowance) for selenium varies by age. For people aged 14 and over, 55 micrograms per day is recommended for the body to function normally.

Dr. Stranges said that selenium levels in soil in United States are higher than the minimum needed to optimize metabolism, so people in the United States should not need to take selenium supplements greater than those in multivitamin supplements.

In an accompanying editorial, Eliseo Guallar, MD, DrPH, from Johns Hopkins University Bloomberg School of Public Health, says the article is “more bad news for supplements.” He says that the NPC trial is the largest and longest experimental study available comparing selenium supplements to placebo, that selenium has a narrow therapeutic range and that at high levels, it can be toxic.

“What the U.S. public needs to know,” Dr. Guallar says, “is that most people in the United States have adequate selenium in their diet. Moreover, taking selenium supplements on top of an adequate dietary intake may cause diabetes.”

Posted by dlifenews at 02:59 PM | Comments (0)

Common Rheumatoid Arthritis Treatment Shows Potential for Diabetes Prevention

July 10, 2007 (EurekAlert) – Far fewer rheumatoid arthritis patients treated with the drug hydroxychloroquine (HCQ) went on to develop diabetes compared to those who never took the drug, according to a 20-plus-year University of Pittsburgh School of Medicine-led study reported today in the Journal of the American Medical Association. In addition, those using HCQ who did develop diabetes were less likely to take medications to manage their disease after diagnosis.

The multi-center observational study of 4,905 adults with rheumatoid arthritis (RA) found that relative risk progressively declined by as much as 77 percent after four years of treatment with HCQ, a common antimalarial medication that also is used for rheumatoid arthritis and other autoimmune disorders.

Additional participating centers in the study are Stanford University, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), one of the National Institutes of Health (NIH) and the University of Cincinnati. Co-investigators at Stanford have directed the project database since its inception with support from the NIH.

“This reduction in risk persisted even after adjusting for other diabetes risk factors among these patients, such as body-mass index, degree of disability and use of corticosteroids,” said rheumatologist Mary Chester M. Wasko, M.D., M.Sc., associate professor of medicine, University of Pittsburgh School of Medicine. Because people with RA tend to be less active and take corticosteroids that can cause weight gain, they are often considered to be at higher risk for developing diabetes, a disease in which blood sugar levels become abnormally high because of the body’s inability to use or produce the hormone insulin.

“Another interesting finding was that the rheumatoid arthritis patients who developed diabetes were less likely to need blood sugar-lowering medication to manage their disease,” said Dr. Wasko, whose clinical research has focused on long-term health improvement in patients with RA. “However, it is most exciting to consider that this drug might be appropriate for people with pre-diabetes as a preventive therapy – much in the same way as a daily baby aspirin is suggested for people at high risk for heart disease.”

Nationally, diabetes is the fifth leading cause of death, according to the American Diabetes Association. Many people first become aware of the disease when confronted with one of its life-threatening complications such as heart disease, blindness, high blood pressure, stroke, kidney disease or circulatory problems that can lead to amputation.

Results show that HCQ’s association with reduction in diabetes risk is comparable or superior to that of a number of other drugs studied in clinical trials for diabetes prevention and treatment, including rosiglitazone, hormones, metformin, acarbose and ramipril. And recent questions have arisen concerning rosiglitazone, marketed as Avandia, and a reported increased risk of heart attack.

Although HCQ is not without side effects – nausea, headache and dizziness, for example – the drug has a long history of being generally safe and well-tolerated. In addition, Dr. Wasko and her colleagues observed no apparent negative interactions between HCQ and other drugs commonly used by RA patients, such as methotrexate and prednisone. An important limitation of the study, however, is that investigators used self-report information from patients collected in follow-up twice yearly that did not include confirmation by laboratory tests.

Other studies of the blood sugar-lowering effects of HCQ have shown minimal use for the drug as a treatment for people with established diabetes, Dr. Wasko continued, stressing the treatment’s real promise may be prevention.

“HCQ already has a role in long-term treatment for RA, potentially moderating lipids and having a weak anti-clotting effect. But, optimistically speaking, endocrinologists can identify people who are at high risk for diabetes, due to obesity, family history, lipid profile or other characteristics. HCQ may also have a role in delaying onset of diabetes,” Dr. Wasko said. “More research is needed to verify our findings in people with RA, and also to determine how this medicine works. But my ultimate hope is that this relatively inexpensive, safe drug will be studied as a way to reduce diabetes risk for people who do not have RA.”

Posted by dlifenews at 10:50 AM | Comments (0)

Alternative Medicines Need to be Considered in Diabetes Management

July 05, 2007

July 5, 2007 (EurekAlert) - People with diabetes are risking their health by not discussing their use of complementary and alternative therapies with the health professionals managing their conventional treatment.

A review of the international health literature has shown nutritional supplements and herbal medicines are the most commonly used complementary and alternative therapies in diabetes.

Annie Chang, a PhD candidate in Griffith’s School of Nursing, said while some products may have benefits for patients, they can also have side effects in their own right or interact with conventional medications.

“Fenugreek for example, used as a supplement, may affect blood sugar levels but patients are already on other blood sugar lowering medications as well.”

While the prevalence of use varies widely between different countries (17-72%), her review suggests nearly half of people living with diabetes supplement their conventional medicines with some form of alternative therapy.

Women, over 65-year-olds, those who had been living with diabetes for longer, and people interested in self management of their condition were the most likely to use alternative therapies.

“People will tell their alternative practitioners that they are using Western medicines but the vast majority will not discuss their alternative therapies with a doctor or other healthcare professional,” she said.

Ms Chang, who has also surveyed more than 300 diabetics in Taiwan, said people feared their doctor would not be interested in discussing alternative medicines or that they might ‘get into trouble’ for taking them.

“The evidence is that patients are using these products and may even reduce their conventional medicine doses and modify the timing of doses so they aren’t taking both together.”

“While it might be impossible for Western medicine to learn all about complementary and alternative therapies, healthcare professionals do need to be included in discussions about them so we can document their use and be aware of any potential problems for our patients.”

Posted by dlifenews at 11:34 AM | Comments (0)

New Study Shows A1c Reduced Safely By Patients With Type 2 Diabetes Using Self-Adjusted Dosing Starting With Once-Daily Insulin Treatment Levemir

June 25, 2007

June 25, 2007 (PRNewswire-FirstCall) -- Novo Nordisk today announced results of a new study that further demonstrated the safety and efficacy of insulin Levemir(R) (insulin detemir [rDNA origin] injection). Patients with type 2 diabetes were able to adjust their own dosage of Levemir(R) and achieve improvements in blood sugar, comparable to dosing adjusted by their primary care physician. This improvement in A1c levels was observed with minimal weight change and without increases in rates of hypoglycemia.(1) The data were presented at the 67th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Illinois.

"The study is a testament to the safety of Levemir(R), as patients were able to adjust their basal insulin dose on their own and achieve the same level of glycemic control as when guided by their doctor, while reducing the risk of hypoglycemia," said Luigi Meneghini, MD, MBA, Associate Professor of Clinical Medicine and the Director of the Eleanor and Joseph Kosow Diabetes Treatment Center at the Diabetes Research Institute, Miami, FL. "Since having type 2 diabetes requires a great deal of self-management, these findings will help empower patients to work more closely as partners with their physician to take control of their insulin treatment. The potential of improved self- management is made possible by insulin analogs like Levemir(R), which provide effective basal insulin coverage, and, as shown in this study, the added benefit of minimal weight change."

The new data were obtained from the insulin detemir 303 Algorithm tested in a Randomized Clinical Trial: The US PREDICTIVE(TM) 303 Trial (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation), which included 5,604 patients. The data showed that patient self-adjustment of insulin treatment with Levemir(R) was as safe and effective when compared to dosing that was adjusted by physicians according to standard-of-care. The patients who self- adjusted their dosage achieved a level of diabetes control that was comparable to that of patients receiving physician-driven adjustments. Minimal weight change was observed in both trial arms.(2)

The findings on weight gain are consistent with previous studies of Levemir(R), the first insulin to show less weight gain versus other basal insulins in 12 of 12 controlled clinical trials*.(3) Weight gain is a common side effect of insulin therapy, which is a concern given that 80 percent of people with type 2 diabetes are overweight or obese.

About the Study (Abstract #197-OR):
The new data presented at ADA were from a six-month analysis of 5,604 type 2 diabetes patients, in a mainly primary care settings, and predominantly treated with Levemir(R) once-daily, as an add-on therapy to any other glucose- lowering regimens, or as replacement of a previous basal insulin. Patients were randomized to either the "303 Algorithm" [self adjusting their Levemir(R) dose every three days based on fasting plasma glucose (FPG)] or "Standard-of- Care" (Levemir(R) dose was physician-adjusted according to standard-of-care) treatment groups.

The study showed that the average A1c, an indicator of long-term blood glucose control, decreased from 8.5 percent at baseline to 7.9 percent at 26 weeks for the 303 Algorithm group, and from 8.5 percent to 8.0 for Standard- of-Care group (p=0.001). Compared to baseline, FPG values decreased by 34 and 21 mg/dL for 303 Algorithm and Standard-of-Care groups, respectively (p<0.0001).

At 26 weeks, 88 percent of all patients remained on once-daily Levemir(R) therapy. In a subset of insulin-naïve patients who added Levemir(R) to their standard-of-care therapy, well over 90 percent of patients remained on a once- daily dosing throughout the 6-month trial. Both groups had a significant improvement in glycemic control, with no increases in hypoglycemia (major hypoglycemic events were .02 event/patient/month for both groups) and minimal weight change (.2 kg for 303 Algorithm group and -.3 kg for Standard-of-Care group).

About Levemir(R)
Levemir(R) (insulin detemir [rDNA origin] injection) is a long-acting insulin analog indicated for once- or twice-daily subcutaneous administration for the treatment of adults and children with type 1 diabetes mellitus and adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia. Levemir(R) has a relatively flat action profile with up to 24 hours duration of action. It can be added to oral anti-diabetic agents, or used in combination with a rapid-acting insulin. Levemir(R) is available in FlexPen(R), a prefilled disposable insulin pen for easy, discreet dosing and in vials.

Levemir(R) was approved by the U.S. Food and Drug Administration in June 2005 and was launched in the U.S. in March 2006. Levemir(R) has been available for use in Europe since March 2004 and is currently approved in 50 countries worldwide. Levemir(R) is contraindicated in patients hypersensitive to insulin detemir or its excipients. Hypoglycemia is the most common adverse effect of all insulin therapies, including Levemir(R). As with all insulins, the timing of hypoglycemic events may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes. Other adverse events commonly associated with insulin therapy may include injection site reactions (on average 3-4 percent of patients in clinical trials) such as lipodystrophy, redness, pain, itching, hives, swelling, and inflammation.

Any change of insulin dose should be made cautiously and only under medical supervision. Concomitant oral antidiabetes treatment may require adjustment. Levemir(R) should not be diluted or mixed with any other insulin preparations or used in insulin infusion pumps. Inadequate dosing or discontinuation of treatment may lead to hyperglycemia and, in patients with type 1 diabetes, diabetic ketoacidosis. Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Dose and timing of administration may need to be adjusted to reduce the risk of hypoglycemia in patients being switched to Levemir(R) from other intermediate or long-acting insulin preparations. The dose of Levemir(R) may need to be adjusted in patients with renal or hepatic impairment.

*Whether the observed differences in weight represent true differences in the effects of Levemir(R) and other therapies is not known, since these trials were not blinded and the protocols (e.g., diet and exercise instructions and monitoring) were not specifically directed at exploring hypotheses related to weight effects. The clinical significance of the observed differences has not been established.

Prescribing information for Levemir(R) is available by contacting Novo Nordisk or visiting novonordisk-us.com.

Posted by dlifenews at 10:45 AM | Comments (0)

Results of Two Head-to-Head Studies Demonstrated Long-Acting Insulin Lantus® Lowered Free Fatty Acid Levels Equal to or Better

June 23, 2007

June 23, 2007 (Sanofi-aventis)- Results from two new head-to-head studies showed that when added to metformin and/or a sulfonylurea, the once-a-day, long-acting insulin Lantus® (insulin glargine [rDNA origin] injection), significantly reduced free fatty acid levels in patients with type 2 diabetes compared to pioglitazone and had comparable effects to rosiglitazone. These results were presented at the American Diabetes Association’s (ADA) 67th Annual Scientific Sessions.

Free fatty acids are released in the bloodstream during the breakdown of fat. High levels of free fatty acids have been linked to a number of serious complications, including insulin resistance. Since people with diabetes have naturally higher levels of free fatty acids, managing these levels effectively is an important component of diabetes treatment.

"High levels of free fatty acid have been shown to affect the regulation of glucose production by the liver and also may impact beta cell function in the pancreas, where insulin is secreted," said Julio Rosenstock, MD, Director of Dallas Diabetes and Endocrine Center at Medical City and also a Clinical Professor of Medicine, University of Texas Southwestern Medical School, Dallas, Texas. "Lipotoxicity generated by the elevated free fatty acid levels, contributes to glucose dysregulation and insulin resistance and plays a major role in type 2 diabetes."

In the first analysis (Change in Lipid Variables With Insulin Glargine (GLAR) vs Pioglitazone (PIO) Added to a Sulfonylurea (SU) or Metformin (MET) - Abstract # 0890-P), which examined the benefits of add-on therapy with Lantus® or pioglitazone in patients inadequately controlled on metformin or a sulfonylurea, the free fatty acid decreases seen with Lantus® were significantly greater than with pioglitazone (week 24: -0.19±0.02 versus -0.13 ±0.02mmol/l, P=0.03, week 48: -0.23±0.02 versus -0.15±0.02mmol/l, P=0.01).

“Physicians and patients face a difficult choice when glycemic control targets are not achieved with metformin or a sulfonylurea,” explained lead study author Janet McGill, MD, Associate Professor of Medicine, Co-Director of the Prevention and Control Core of the Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri. “This study is particularly timely, as the need for a better understanding of the metabolic affects associated with rosiglitazone, pioglitazone and Lantus® has never been greater.”

The most common adverse events in this study were infections and infestations, nervous system disorders, musculoskeletal and connective tissue disorders, general disorders and administration-site conditions, and gastrointestinal disorders. Overall, hypoglycemia and severe hypoglycemia occurred more frequently with patients treated with insulin glargine as compared to those treated with pioglitazone.

The second analysis (Free Fatty Acid (FFA) Changes with Insulin Glargine (GLAR) vs Thiazolidinediones (TZDs) According to Baseline A1C in T2DM - Abstract # 0889-P) also compared the free fatty acid-lowering effects of add-on therapy with Lantus® versus TZDs, including a comparison with rosiglitazone (study 2) as well as pioglitazone (study 1). Patients were grouped using baseline A1C (an important test that measures average blood glucose control over a two- to three-month period) scores by low, middle, and high levels (Chart 1).

After 24 weeks, mean decreases in free fatty acid were significantly greater with Lantus® versus pioglitazone in the middle (-0.19±0.03 versus -0.09±0.03mmol/L, P=0.02) and high (-0.24±0.03 versus -0.13±0.03mmol/L, P=0.02) A1C groups (chart 1, study 1).

The baseline A1C-dependent effect on free fatty acid levels may be more pronounced with Lantus®, possibly reflecting greater A1C reductions in patients with higher baseline A1C.

In the comparison between Lantus® and rosiglitazone, free fatty acid decrea