Could Avandia’s safety risks be avoided just by lowering the dose? A new study suggests it. Published in the Lancet, the study tested half doses of Avandia in combination with the commonly used diabetes drug metformin against placebo–and it found that the drug combo cut the risk of developing diabetes by two-thirds. And the patients taking this low-dose cocktail didn’t develop the weight gain or heart problems associated with higher Avandia doses, the researchers say.

Of course, more study is needed to confirm that safety-risk news, the Lancet notes. “The side-effect profile for the low-dose combination looks favorable,” a commentary accompanying the study asserts. “However, that conclusion is not yet definitive.”

Even a suggestion of good news is a positive for Avandia. The drug has been on the decline since May 2007, when a New England Journal of Medicine report linked the GlaxoSmithKline drug to a 43 percent increased risk of heart attack. Since then, the drug has been slapped with FDA warnings, and GSK has launched a head-to-head safety study with Takeda’s rival drug Actos.

Now, that safety study is drawing criticism from medical ethicists and consumer advocates, while the FDA prepares for another advisory panel review of Avandia’s risks. Some are calling for Avandia to be withdrawn altogether. If dosing changes can mitigate the possibility of serious side effects, FDA and GSK could have themselves a solution.

Source: FiercePharma

Popularity: 3% [?]

Low doses of GlaxoSmithKline’s diabetes drug Avandia combined with metformin can prevent diabetes without causing the most common side-effects, Canadian doctors reported on Wednesday.

Taking half a dose of Glaxo’s combination pill reduced by two-thirds the risk that patients would go from having high blood sugar — pre-diabetes — to full type-2 diabetes, the researchers reported in the Lancet medical journal.

Fourteen percent of the patients treated with the drugs developed diabetes after four years, compared to 39 percent of those given placebo, the researchers found.

The effect would likely be the same with Avandia’s rival drug in the same class, Takeda’s Actos, said Dr. Bernard Zinman of Mount Sinai Hospital at the University of Toronto, who led the study.

“I think it is a class effect,” Zinman said in a telephone interview.

Actos, known generically as pioglitazone and Avandia, known generically as rosiglitazone, belong to a class of drugs called thiazolidinediones, which help the body better use insulin.

Type-2 diabetes is caused as the body gradually loses its ability to respond to insulin, a condition called insulin resistance. Overeating, a lack of exercise, genes and other factors all play a role.

As insulin works less and less well, levels of glucose rise in the blood, damaging blood vessels and organs. The beta cells in the pancreas begins to lose their ability to make insulin.

SIDE-EFFECTS

Avandia and Actos work well to help and even prevent diabetes. But they have side-effects, including fluid retention, heart failure and, possibly, heart attacks.

Glaxo said this week it had settled more lawsuits alleging Avandia caused heart attacks.

The U.S. Food and Drug Administration is reviewing data on possible heart risks from the drug.

Glaxo, which will be looking to save its faltering market for Avandia, paid for the study. Sales of Avandia topped $3 billion in 2006, but fell to $1.2 billion in 2009.

Metformin is an older drug that also helps the body use insulin, but it can cause upset stomach.

So Zinman decided to try a half-dose of both to see if that would be effective and cut back the side-effects.

His team recruited 207 patients with pre-diabetes and gave them either two pills a day of combined Avandia and metformin or placebos. They followed them for almost four years.

“The side-effects were not there — the weight gain, fluid retention, the gastrointestinal side-effects,” Zinman said.

The study has not lasted long enough to tell whether heart failure or heart attack rates would rise measurably, but Zinman said fluid retention often points to future potential heart effects.

Both Avandia and Actos will soon be available generically, and metformin has long been, meaning a potentially inexpensive way to prevent diabetes, he said.

Lifestyle changes like exercising and losing weight also work to prevent diabetes, but people do not follow them well, he noted.

“The concept of combining submaximum doses of effective drugs to maintain efficacy and reduce side-effects is an attractive one,” Dr. Thomas Buchanan of the University of Southern California wrote in a commentary.

The International Diabetes Federation estimates that 300 million people worldwide have pre-diabetes and 230 million have diabetes.

Source: Reuters

Popularity: 3% [?]

A period of careful eating and regular exercise can stave off diabetes for a decade, a study suggests.

US researchers followed up nearly 3,000 overweight people who had taken part in a three year diabetes prevention programme.

The group had initially been divided into three – assigned either to a diet and exercise programme, the diabetes drug metformin or a placebo.

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The Lancet report notes it was the dieters who reaped the most benefit.

All three groups were given access to ongoing lifestyle coaching once the initial three year trial had ended.

That trial, carried out by the US-based Diabetes Prevention Program Research Group, had shown a diet aimed at achieving 7% weight loss, combined with half an hour of exercise five days a week, reduced the risk of developing Type 2 diabetes by 58% compared with the placebo group.

The group on metformin, a drug which has been used to treat the condition since the 1950s, saw their risk decline by nearly a third.

In the seven years after the trial ended, both the drug and placebo groups – now also eating more carefully and exercising – saw the rate of diabetes fall.

But the most significant drop was among those who had started out on a diet and exercise regime – their risk was over a third lower than the placebo group.

In an accompanying editorial, Dr Anoop Misra, a specialist in diabetes in New Delhi, described the prevention of the disease as “a long and winding road”.

‘No short cut’

Dr Misra said: “There seems to be no short cut, and a persistent and prolonged intensive lifestyle intervention seems to be the most effective way to travel on it.”

But he warned it could not be the only measure: “We need more effective drugs for those who cannot follow intensive lifestyle therapy because of infirmity.”

Type 2 diabetes usually appears in people over the age of 40, however increasing numbers of children are being diagnosed with the condition, some as young as seven.

Although obesity is a risk factor, not all people with type 2 diabetes are overweight.

Dr Iain Frame, head of research at Diabetes UK, said: “It is fascinating to read about the 10-year follow up studies and of the importance of lifestyle interventions, with or without metformin, in the prevention of Type 2 diabetes even after 10 years.

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“There is clearly no easy route to take to prevent Type 2 diabetes but indications are that with further research into the long-term benefits of good dietary advice, physical activity and, where necessary drug therapies, we may be a step closer into helping people at high risk of developing Type 2 diabetes modify their lifestyle choices that are sustainable in the longer term.”

Source: BBC NEWS

Popularity: 3% [?]

In the first Phase III study of Bristol-Myers Squibb and AstraZeneca’s diabetes drug, dapagliflozin met both primary and secondary endpoints. When used with the common diabetes drug metformin, the drug reduced blood glucose levels and fasting plasma glucose  in patients with type 2 diabetes inadequately controlled with metformin.

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Dapagliflozin is part of a new class of drugs called SGLT2 inhibitors. The protein SGLT2 helps the body retain glucose for its energy requirements. But for patients with diabetes, glucose retention leads to persistent high blood sugar. SGLT2 inhibitors suppress this protein so that excess glucose is excreted from the body rather than reabsorbed.

Analysts project dapagliflozin sales at $1.5 billion, though they will keep an eye on potential safety issues with the drug. “Dapa’s (dapagliflozin’s) unprecedented efficacy offering for an oral anti-diabetic agent–with what we see as a manageable safety profile–puts it on a trajectory to be a risk-adjusted global blockbuster,” UBS said in a research note, as quoted by Reuters. Barring any problems, approval is anticipated in 2010 or early 2011.

Source: FierceBiotech

Popularity: 2% [?]

The FDA said today that Merck’s diabetes drug Januvia may be associated with pancreatitis, a serious inflammation of the pancreas that can lead to hospitalization and, in rare cases, death. Merck said that the data suggest the drug doesn’t cause pancreatitis.

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This is the second time in just over a year that a popular, new-ish diabetes drug has been linked to pancreatitis — the previous case was Byetta, which is co-marketed by Amylin and Eli Lilly. In that instance, several deaths were reported.

The FDA said today it had received 88 reports of pancreatitis in patients taking Januvia and Janumet, a related drug that combines Januiva with the diabetes medicine metformin. The agency didn’t report any deaths in cases of pancreatitis in patients taking the drugs, but 66% of the cases did require hospitalization. In 21% of cases, pancreatitis occurred within 30 days of starting Januvia or Janumet; 53% of the cases resolved once after the drug was discontinued.

Merck said that data from clinical trials that included more than 6,000 people, as well as reports that have emerged since the drug has been on the market, don’t show an increased risk of pancreatitis associated with Januvia. The statement notes that simply having diabetes increases the risk of the disorder.

Amylin and Lilly have been named as defendants in Byetta cases brought by 110 plaintiffs in cases primarily related to pancreatitis, Amylin said in its most recent quarterly report. Byetta sales fell slightly in the first half of this year, to $332.8 million from $336 million in the year-earlier period.

Byetta and Januvia are different classes of drugs. But they work in related ways. Januvia slows the breakdown of a hormone known as GLP-1 and a related hormone; Byetta mimics naturally occurring GLP-1.

Merck’s sales of Januvia and Janumet totaled more than $1 billion in the first six months of this year.

Source: The Wall Street Journal

Popularity: 4% [?]

Eli Lilly, Amylin and Alkermes reported Monday that patients with type 2 diabetes who took exenatide once weekly had a significant reduction in A1C levels compared with those who took sanofi-aventis’ Lantus (insulin glargine). The companies also said that use of the long-lasting GLP-1 analogue in the head-to-head trial resulted in a significant reduction in weight versus sanofi-aventis’ product.

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The DURATION-3 study enrolled 467 patients with type 2 diabetes who were not achieving adequate glucose control with metformin alone or in combination with a sulphonylurea. Patients were randomly assigned treatment with either exenatide once weekly, or once-daily doses of Lantus. Following the 26-week treatment period, data for the primary endpoint showed that A1C levels were reduced by 1.5 percentage points from baseline among those administered exenatide once weekly, compared to a drop of 1.3 percentage points for Lantus-treated patients. Both groups started with a baseline A1C level of 8.3 percent.

Furthermore, findings at 26 weeks showed that treatment with exenatide once weekly resulted in a mean weight loss of 5.8 pounds, compared with a mean weight gain of 3.1 pounds in the Lantus group, the companies stated. Eli Lilly, Amylin and Alkermes submitted the treatment for review by US regulators earlier this year.

The twice-daily version of the diabetes drug, Byetta, was approved in 2005 and generated global sales of $751 million last year.

Source: FirstWord

Popularity: 5% [?]

AstraZeneca and Bristol-Myers Squibb announced Thursday that their application for Onglyza (saxagliptin) received a positive opinion from the EMEA’s Committee for Medicinal Products for Human Use for the treatment of type 2 diabetes. The DPP-4 inhibitor has been recommended for adults as an add-on therapy with metformin, a thiazolidinedione or a sulphonylurea.

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The companies said the positive opinion was reached after the CHMP reviewed data from a clinical development programme that included six Phase III trials assessing the safety and efficacy of Onglyza as a once-daily therapy. These studies involved 4,148 patients with type 2 diabetes, including 3,021 patients treated with Onglyza.

In the US, the drug received backing from an FDA advisory panel in April. Later that month, the agency announced that it was extending its review of the drug by three months to July 30.

Source: FirstWord

Popularity: 4% [?]

Takeda announced Thursday that it will delay the EU filing of experimental type 2 diabetes drug alogliptin, as well as a treatment combining the compound with Actos (pioglitazone), by about two and a half years to 2012 in order to conduct an additional long-term clinical study on the DPP-4 inhibitor. Company spokesperson Toshiyuki Ikeuchi said “the test would help us win approval with more certainty.”

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The two-year study will enrol almost 2500 subjects with type 2 diabetes, whose blood glucose level is inadequately controlled with metformin, and will evaluate “alogliptin compared to glipizide when used in combination with metformin.”

The move follows an announcement earlier this year that the FDA, which is currently reviewing alogliptin and is scheduled to render a decision by June 26, requested more data for the drug. A Takeda spokesperson specified that the decision to conduct a new trial was made without prompting by EU regulators and said the trial will be separate from an additional study planned for the US market.

Commenting on the development, analyst Yo Mizuno of the Daiwa Research Institute said “the delay in Europe is not a surprise… It has been largely expected, as a delay in the US of one to two years has become the market consensus.”

Source: FirstWord

Popularity: 4% [?]

A common anti-diabetes drug may boost the potency of vaccines against cancer, research suggests.

Tests on mice found metformin, used for Type 2 diabetes, helps the body’s T-cells work more effectively.

These cells, the body’s key defenders against disease, “remember” former infections or vaccinations, enabling them to fight subsequent illness.

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Writing in the journal Nature, a US team said metformin appeared to improve this important memory of disease.

This ability to remember disease has been the subject of much research, but there has been little understanding of the cellular mechanisms behind it.

The team from McGill University and the University of Pennsylvania used an experimental cancer vaccine and found that when administered in mice, the diabetes drug appeared to improve the strength of the inoculation.

Diseases ‘linked’

Several studies in recent years have shown that people with diabetes may be more likely to develop certain cancers, although the exact nature of the relationship is unclear. Type 2 diabetes is associated with extra weight for instance, as are certain types of cancer.

But there also appear to be similarities between the basic chemical reactions which happen in the cells when affected by either of these diseases.

“Many genes involved in diabetes regulation also play a role in cancer progression,” said Dr Russell Jones of McGill’s Goodman Cancer Centre, one of the report’s author.

“There is also a significant body of data suggesting that diabetics are more prone to certain cancers. However, our study is the first to suggest that by targeting the same metabolic pathways that play a role in diabetes, you can alter how well your immune system functions.”

This is turn could help the body fight cancer more effectively with a vaccine.

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Cancer vaccines are still at an early stage, but ideally could help both stop the disease developing in the first place or treat it when it arises.

Dr Kat Arney, Cancer Research UK’s senior science information officer, said: “This is a fascinating piece of research, which sheds light on the complex links between the immune system, cell metabolism and cancer.

“At the moment, this research has only been done in mice and there is a long way to go before it can be applied to cancer patients, but it certainly holds promise for the future.”

Source: BBC NEWS

Popularity: 4% [?]

GlaxoSmithKline announced Tuesday that the company began late-stage testing of experimental GLP-1 agonist Syncria (albiglutide) for the treatment of type 2 diabetes. The Phase III programme will involve five studies and more than 4000 patients.

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The primary endpoint for all the studies will be the change from baseline in HbA1c compared with placebo and/or active comparators, such as metformin, sulphonylurea, thiazolidinedione, insulin and a dipeptidyl peptidase four inhibitor.

Other GLP-1 agonists include Eli Lilly and Amgen’s Byetta (exenatide) and Novo Nordisk’s experimental liraglutide, and WestLB analyst Simon Mather suggested that if both these drugs “swallow up the market then it might be quite hard to get market share, but if (Syncria is) shown to have a better safety profile and better efficacy, then potentially it could generate quite good revenue.”

Source: FirstWord

Popularity: 5% [?]