Type 1 Diabetes Drug Proves Effective in Clinical Trial

An experimental drug designed to block the advance of type 1 diabetes in its earliest stages has proven strikingly effective over two years in about half of the patients who participated in the phase 2 clinical trial.

Jeffrey Bluestone, PhD

Patients who benefited most were those who still had relatively good control of their blood sugar levels and only a moderate need for insulin injections when the trial began. With the experimental drug, teplizumab, they were able to maintain their level of insulin production for the full two years – longer than with most other drugs tested against the disease.

Results are published online in the journal Diabetes, and will appear in the November issue of the print edition.

The treatment did not benefit all patients. Some lost half or more of their ability to produce insulin – a drop similar to many of the controls not receiving the drug. Reasons for the different responses are unclear, but likely involve differences in the metabolic condition of the patients and in the severity of their disease at the trial’s start, the researchers said.

Kevan Herold, MD, PhD

“The benefits of treatment among the patients who still had moderately healthy insulin production suggests that the sooner we can detect the pre-diabetes condition and get this kind of drug onboard, the more people we can protect from the progressive damage caused by an autoimmune attack,” said Jeffrey Bluestone, PhD, co-leader of the research and A.W. and Mary Clausen Distinguished Professor at UC San Francisco, who collaborated in developing the drug. 

The clinical trial was led by Kevan Herold, MD, PhD, a professor of immunobiology and deputy director for translational science at Yale University. He and Bluestone have collaborated on four previous clinical trials of the experimental drug.

“We are very excited by the efficacy of the drug,” Herold said. “Some of our patients and families have described a real impact on their diabetes.”

Bluestone, an immunologist who is now executive vice chancellor and provost at UCSF, developed teplizumab in collaboration with Ortho Pharmaceuticals in 1987. He is a leader in research that aims to understand how and why the immune system attacks the body’s own tissues and organs, and to develop drug strategies to eliminate the autoimmune response without producing severe side effects.

Catching Diabetes in Earliest Stages

The results underscore the importance of diagnosing and treating diabetes in its earliest stages, the researchers said. Current treatment studies include “pre-diabetes” patients who have abnormal blood sugar levels but do not need to take insulin.

Formerly referred to as juvenile diabetes because it disproportionately strikes children, type 1 diabetes is caused by an autoimmune condition in which the body’s immune system destroys insulin-producing beta cells in the pancreas. Even with insulin treatments, the blood glucose levels fluctuate abnormally, and as the disease progresses, diabetes increases the risk of kidney failure, heart disease and other serious disorders.

According to JDRF, as many as 3 million American have type 1 diabetes, and each year, more than 15,000 children and 15,000 adults are diagnosed with the disease in the United States. For reasons still unknown, the incidence of type 1 diabetes is increasing, and the age of onset is decreasing.

Controlling Autoimmune Reactions

Teplizumab is one of a number drugs under active investigation to control autoimmune reactions. Teplizumab uses an antibody targeted against a molecule called CD3 to bind to the immune system’s T-cells and restrain them from attacking beta cells.

Immunotherapies are designed to treat organ transplant rejection and autoimmune diseases, including multiple sclerosis, Crohn’s disease, rheumatoid arthritis and asthma. The use of these agents in type 1 diabetes is emerging based on work in preclinical models and clinical trials.

The journal’s print edition will include a commentary by Jay S. Skyler, MD, chairman of the National Institutes of Health-funded Type 1 Diabetes Trial Net, an international network of researchers that also studies teplizumab for prevention of type 1 diabetes. Skyler writes that the new results make a compelling case for U.S. Food and Drug Administration approval to launch a much larger-scale, phase 3 clinical trial of the drug’s effectiveness.

The study focused on 52 participants, most of whom were less than 14 years old, who had been diagnosed with “new-onset type 1 diabetes” within eight weeks of the trial’s start. All 52 were treated with the experimental drug for two weeks at diagnosis and again one year later, and their capacity to produce their own insulin to control their blood sugar was compared with a non-treated group.

Because the participants received daily insulin injections before and throughout the trial, researchers instead monitored their blood levels of C-peptide, a molecule produced in the pancreas at the same rate as insulin.

Watch this video to learn more about the groundbreaking work of the UCSF

Diabetes Center.

This research was a project of the Immune Tolerance Network (NIH contract #NO1 AI15416), an international clinical research consortium supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation. It also was supported by NIH grants UL1 RR024131 and UL1 RR024139.

Co-authors on the paper and collaborators in the clinical trial with Herold and Bluestone include Stephen E. Gitelman, MD, UCSF; Mario R. Ehlers, PhD, and Peter H. Sayre, MD, of the Immune Tolerance Network (ITN), San Francisco; Peter A. Gottlieb, MD, University of Colorado;  Carla J. Greenbaum, MD, Benaroya Research Institute, Seattle; William Hagopian, MD, Pacific Northwest Diabetes Research Institute, Seattle; Karen D. Boyle, MS, and  Lynette Keyes-Elstein, DrPh, Rho Federal Systems Division, Chapel Hill; Sudeepta  Aggarawal, PhD, and Deborah Phippard, PhD, ITN, Bethesda; James McNamara, MD, National Institutes of Allergy and Infectious Diseases.

Conflict of interest statement: Jeffrey Bluestone has a patent on the teplizumab molecule. Kevan Herold has received grant support from MacroGenics, Inc., a company that owns rights to the drug.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Diabetes drug back with warning, but will patients swallow the pill?

Govt directive warns that Pioglitazone should not be first line of therapy

Diabetes drug pioglitazone and its combinations are back, but with a box warning in “bold red letters” to caution patients.

For a drug suspended a month ago for its possible links to urinary bladder cancer, its revocation could end up being a tough pill to swallow, especially for new patients with type II diabetes, say doctors.

Patients who have controlled diabetes with pioglitazone may still go back to the drug, says diabetologist Rajiv Kovil.

But putting new patients on pioglitazone may fall by at least two-thirds, he says, as they would be “extremely anxious”.

An engineer by profession, 43-year-old Rishi Kumar, for instance, would not like to take the medicine, now that he has doubts about its safety. He would, in fact, go for a second opinion if he is prescribed the medicine again.

Warnings

Pioglitazone is used as a third line of treatment. In its latest directive, the Government has emphasised the need for caution, insisting that the drug not be used as the first line of therapy, says Kovil.

The Government has brought back pioglitazone with several riders. Doctors need to run tests on the patient before initiating treatment, restrict use of the drug in elderly patients and prescribe it only after knowing the patient’s history.

It also requires patients on pioglitazone to be put through 3-6 monthly reviews.

Diabetologist V. Mohan is happy that, after much discussion, the Government has laid down several conditions on the use of pioglitazone. He was also involved in the discussions on pioglitazone and its suspension.

Patients will go by what the doctor says, and the doctor needs to share all these risks with the patient before starting the drug, he points out.

Precisely the sentiment of 69-year-old A.N. Dutta, suffering from type-2 diabetes for 10 years.

“I would not like to second-guess my doctor on this issue. Ultimately, it is about having faith in your doctor’s judgment. Now that the ban has been revoked, if he prescribes the medicine (piloglitazone) again, I will take it,” he says.

jyothi.datta@thehindu.co.in

aesha.datta@thehindu.co.in

Ban on diabetes drug leaves patients crippled

After the government imposed a ban on widely used anti-diabetes drug pioglitazone, city patients and diabetologists are in the dock.
The drug, which is quite popular with Type 2 diabetes patients, is consumed by about 10% of city’s population, claimed city diabetologist Dr Abhay Mutha at a press conference on Friday.

Chief diabetologist at Ruby hall Clinic, Mutha said, “The ban of pioglitazone came as a rude shock to us. It is one of the most prescribed medicines to our patients suffering from Type 2 diabetes. The medicine, being cheap and highly effective with minimum side effects is also used widely in western countries.”
Mutha said that the reasoning for the ban wasn’t clear and that government officials should consult the medical practitioners and reconsider the decision.

Diabetologist Dr Shrirang Godbole said that with the ban, the only available option that doctors have for the patients is to prescribe alternative medication or initiate the use of insulin. “I have been receiving frantic calls from my patients regarding the same,” he said.

There are other drugs available in the market with varying pioglitazone combination, but they are less effective, said Mutha.

US considers lifting safety limits on blockbuster diabetes pill

A former blockbuster diabetes pill which was subjected to major US safety restrictions in 2010 may not be as risky as once thought, according to the latest analysis of the much-debated GlaxoSmithKline drug Avandia.

The Food and Drug Administration is reviewing a new interpretation of the key study of Avandia’s heart attack risks, which suggests the drug is as safe as older diabetes drugs. At a highly unusual meeting this week, the FDA will ask a panel of experts to vote on a range of options for the drug, including lifting restrictions on its use.

The positive safety review from Duke University researchers is the latest twist in a years-long debate over Avandia, which has divided medical experts, cost Glaxo billions of dollars and possibly resulted in an unknown number of patient heart attacks.

First approved in 1999, Avandia became the top-selling diabetes pill in the world by 2006 with sales of $3.4 billion. But prescriptions plummeted the following year after an analysis of dozens of studies suggested Avandia could raise the risk of heart attack.

For three years the FDA struggled to answer a seemingly simple question: Does Avandia increase the risk of heart attacks? A definitive answer has never been reached, in part because patients with diabetes are already predisposed to heart problems. That makes it extremely difficult to tell which heart attacks are drug-related and which are simply a result of the underlying disease.

Finally in 2010 the FDA decided to restrict the drug’s use to all but the rarest of cases. Regulators in Europe banned the drug outright.

FDA critics have speculated that the real purpose of this week’s meeting is to vindicate FDA officials who kept Avandia on the market for so many years. They say regulators appear poised to roll back safety limits on the drug.

… contd.


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Billy Ray ‘so sad’ about Miley Cyrus bong video

Country singer Billy Ray Cyrus took to his Twitter to express his dissappointment about the video of his daughter Miley that is circulating the internet.

The clip, which was posted by TMZ.com, was filmed at a belated birthday party for the 18-year-old star at the family’s Los Angeles mansion last month and shows her smoking a bong.

“Sorry guys,” he wrote to his followers. “I had no idea. I’m so sad. There is much beyond my control right now.”

Miley is seen in the clip taking a hit of what is reportedly Salvia, a natural but powerful hallucinogenic drug, and almost instantly she starts giggling uncontollably and rambling incoherently.

At one point the singer then turns to camera and laughs: “OK, I’m about to lose it now.”

Shortly afterwards Miley says: “[I’m] having a little bit of a bad trip,” and then she asks “Is that a f***ing Liam lookalike or what the hell is that? Is that my boyfriend?

“Oh my God, he looks so much like him. Is that me tripping?”

A friend filming her says: “You’re gonna sh*t a brick when you see this,” to which a very high Miley replies: “Oh no. I want more of this sh*t, I swear.”

The video was reportedly stolen or copied from the friend’s camera.

Anthony Adams, a former CA State Assemblyman told TMZ it was irresponsible of the young star to smoke the drug — legal in California and some other states in America — which he said can make “you do incredibly crazy things.” Do you think it should be banned?

Read here about the effects of Salvia divinorum.

Images: PR Photos and Wikimedia Commons

Greg Giraldo critical after prescription drug overdose

Comedian and judge of the show ‘Last Comic Standing’, Greg Giraldo is in a critical condition following an overdose of prescription drugs on Saturday night, says a report published in www.msnbc.com. He was staying in a hotel in New Jersey when the incident took place.

Earlier in the day, he had to perform at an event to support the Drug Addiction Recovery Month. Earlier, at a party at the hotel where he was staying, according to an eye witness, Greg was found to be unresponsive. The eye witness described the bash as being like a zoo. Greg was resuscitated by the medical team that arrived at the site and took him to Robert Wood Johnson University Hospital, which is located near Brunswick.

The drug overdose was an accident and not a suicide attempt, says a report in www.popeater.com. His condition is believed to be stable. The provocative and wildly funny comedian was performing at the Stress Factory comedy club and was staying at the hotel when the incident took place. People who came to attend the show were told that Giraldo has been rushed to the hospital but the reason was kept undisclosed.

Celebrities who have died from a drug overdose include Anna Nicole Smith, Brittany Murphy, John Belushi, Heath Ledger and River Phoenix

Images: http://www.sxc.hu/browse.phtml?f=download&id=1095556, http://upload.wikimedia.org/wikipedia/en/5/53/Ggiraldo_SF.jpg

Lindsay Lohan fails drug test

Lindsay Lohan has failed her most recent drug test, and claims she is “ready to face the consequences”. In a series of messages on her Twitter account, Lindsay wrote:

“Regrettably, I did in fact fail my most recent drug test.

“Substance abuse is a disease, which unfortunately doesn’t go away over night. I am working hard to overcome it and am taking positive steps forward every day. I am testing every single day and doing what I must do to prevent any mishaps in the future.

“This was certainly a setback for me but I am taking responsibility for my actions and I’m prepared to face the consequences.

“I am so thankful for the support of my fans, loved ones and immediate family, who understand that i am trying hard, but also that I am a work in progress, just as anyone else. I am keeping my faith, and I am hopeful….Thank you all!!!”

Lindsay has only just been released from her sentence that saw her spend nearly two weeks in a prison and just over three weeks in rehab following violations she committed in regards to a 2007 DUI case.

She is currently receiving intense outpatient treatment after leaving the facility two months earlier than was initially ordered. A part of her outpatient program includes two random drug tests every week until her next hearing in November.

The new judge in the case had warned Lindsay that failed drug tests would immediately see her land back in jail for another 30 days. Lindsay said she is ready to face Judge Fox: “If I am asked, I am prepared to appear before judge Fox next week as a result,” she tweeted.

Read our complete coverage on Lindsay Lohan, including Lindsay’s release from rehab, Lindsay turning herself in for prison, what addictions Lindsay has, and whether Lindsay battled an eating disorder.

Images: PR Photos

Paris Hilton makes excuses after being caught with cocaine

Friday night saw the arrest of Paris Hilton in Las Vegas as she was convicted of carrying cocaine, says a report in www.people.com.  The police stopped her car on the way as they noticed marijuana smoke coming out of it when the car was in front of the Wynn Hotel.

The police conducted a search and found cocaine in Paris’s purse. According to reports, a small pouch containing cocaine fell out of the purse when she was looking for some lip balm. Paris then reportedly didn’t recognize the cocaine, and asked if it was gum.

According to the report published in www.eonline.com, the small bag that fell out of her bag contained .8 grams of cocaine. Hilton is now being charged for felony drug possession and the arrangement has been set for October 27. She could face up to four years in prison.

She denied owning the baggie and said that the purse was not hers. She said that she had borrowed the purse from a friend and the content in the purse was not all hers. There was an Albuterol pill, zig-zag wrappers, $1300 cash and credit cards in the purse that she said were hers. There were some cosmetics inside the purse that she said belonged to her friend.

She was first arrested early in the morning but was released later. This was the third time that Paris had been involved in a drug related case.

Celebrities who have admitted to taking drugs include Kendra WilkinsonDrew BarrymoreCharlie Sheen and Mickey Rourke.

Images: PR Photos