Research - Diabetes Drugs
Actos - Diabetes Medication
Every medication is capable of causing side effects and potential complications, but some medications cause side effects and complications that are more harmful or even deadly in nature. The diabetes medication known as Actos has been approved for use by the Food and Drug Administration, and therefore was considered to be safe. Unfortunately, recent studies have revealed that there is link between Actos and bladder cancer. Actos has also been linked with a number of other serious or potentially serious side effects.
As a result of these recent studies, the Food and Drug Administration is now monitoring two long-term studies on the impact on Actos on the body. While this drug is an effective diabetes treatment, the implications of the drug's potential side effects simply cannot be ignored. This is not the only drug that is currently being scrutinized by the Food and Drug Administration because there are other drugs that contain the primary ingredient, pioglitazone hydrochloride.
Some of the most common side effects associated with the use of pioglitazone hydrochloride include: upper respiratory infections, headache, sinus infection, muscle pain, dental problems, sore throat and swelling.
* Upper respiratory infections, for example, are estimated to occur in as many as 13.2 percent of all people taking the drug.
* Headache occurs in as many as 9.1 percent of all users and sinus infections occur in as many as 6.3 percent of all users.
* Muscle pain impacts up to 5.4 percent of all users and dental problems impact as many as 5.3 percent of all users.
* Sore throat and swelling or edema can affect as many as 4.8 to 5 percent of all users, and there is a direct relationship between Actos and weight gain for many users of the drug.
The most devastating complication associated with Actos is that when used for longer than one year, this diabetes medication is capable of significantly increasing the risk of developing bladder cancer. People who have taken the drug for longer than one year have experienced bladder cancer symptoms or a bladder cancer diagnosis. This has lead many Actos users to file an Actos lawsuit.
This medication is currently being investigated not only for the bladder cancer risk that it may be increasing, but also for a potential in causing other types of cancer as well. Actos may also be linked to liver cancer, prostate cancer and kidney cancer as well though there are no definitive answers yet and it will be some time before these studies reveal any hard evidence in either direction.
People with diabetes who are currently taking this drug or who have taken it in the past for a period of longer than one year are urged to consult a physician and to be on the lookout for symptoms relating to bladder cancer. The most common symptoms pointing to bladder cancer include difficulty urinating, pain while urinating, red coloration in the blood, urine in the blood and unexplained abdominal pain.
If someone who is taking Actos or who has taken it in the past is experiencing any of these symptoms, the Food and Drug Administration urges that patient to seek assistance from a physician as soon as possible.
Source : drugwatch.com
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FDA reviewing safety of Actos diabetes drug
The Food and Drug Administration said on Friday it was reviewing if Takeda Pharmaceutical Co Ltd's blockbuster diabetes drug Actos may be linked to bladder cancer.
Actos is the Japanese drugmaker's top-selling product with sales of about $4 billion a year, but the pill is due to face generic competition after it loses U.S. patent protection in January 2011.
The FDA said early data from an ongoing Takeda study showed no overall association with Actos and bladder cancer. But an increased risk of bladder cancer was seen among patients with the longest Actos exposure and the highest cumulative doses.
The preliminary results are based on 5-year data from an ongoing 10-year trial by Takeda.
"At this time, FDA has not concluded that Actos increases the risk of bladder cancer," the agency said in a statement.
Patients should not stop taking Actos unless told to do so by their doctor, the agency said.
Takeda said the results were early, and the company was committed to completing the 10-year study to get a better picture of bladder cancer rates.
"Looking at the completion of the study will give us the most accurate look at that," Dr. Robert Spanheimer, Takeda medical director for Actos, said in an interview.
Actos is in the same class of drugs as GlaxoSmithKline PLC's Avandia, which has not been associated with bladder cancer but has been linked to heart risks in some studies. Glaxo has said overall scientific evidence does not show that the drug increases heart attack risk.
The FDA is weighing whether Avandia should stay on the market with new restrictions or be removed. In July, an advisory panel voted 20-12 in favor of keeping the drug on the market, although many urged tight restrictions.
Avandia's opponents have argued that the drug is too dangerous to be sold and they have pointed to Actos as a safer alternative. Actos sales have grown while use of Avandia, or rosiglitazone, fell amid a debate about risks.
Concerns about bladder cancer arose with Actos, or pioglitazone, from cases seen in male rats. The drug's prescribing instructions mention those findings.
A guide for patients also notes that bladder cancer occurred in "a few more people who were taking pioglitazone than in people who were taking other diabetes medicines," but adds, "There were too few cases to know if the bladder cancer was related to pioglitazone."
Bladder cancer occurs in an estimated 20 per 100,000 people per year in the United States and is thought to be higher in diabetics, the FDA said.
Source: Reuters 17/9/2010
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Diabetes drug Avandia still available despite suspension advice
A drug for type two diabetes is still being prescribed in the UK despite being recommended for withdrawal two months ago, BBC Panorama has found.
Avandia has been linked to a raised risk of heart attacks and heart failure and is under a Europe-wide review.
An expert panel of the UK Medicines and Healthcare products Regulatory Agency (MHRA) said its use should be suspended but it is still available on the NHS.
Manufacturer GlaxoSmithKline (GSK) said it was safe if properly monitored.
'Alternative treatments' Tens of thousands of patients take Avandia, also known as Rosiglitazone. It was prescribed more than one million times in the UK last year alone.
Pharmaceutical giant GSK said its research programme proved the drug was "safe and effective when it is prescribed appropriately".
Clinicians at the MHRA's advisory body, the Commission on Human Medicines (CHM), voted unanimously in July for Avandia's withdrawal from the UK. But the recommendation was not made public.
The MHRA said following the advice it sent letters to healthcare professionals asking them to "consider alternative treatments where appropriate".
It also said it used the information to push for a UK withdrawal as part of the Europe-wide review by the European Medicines Agency.
The drug is meant to improve life for type two diabetics by helping to regulate blood sugar levels but there is also evidence it could increase the risk of heart failure and heart attacks.
Swelling "Doctors were advised not to use the tablet in anyone who was at risk of heart failure," said Prof Edwin Gale, a leading UK diabetes expert.
Prof Gale, who chairs the European Medicines Agency scientific advisory group on diabetes, said Avandia should be withdrawn entirely.
"How long do you wait? How important is it to be absolutely certain and at what point do you start saying - this game isn't worth it, people's lives may be at risk, something should be done about it?" he said.
Clinical pharmacologist Dr Yoon Loke, of the University of East Anglia, said his analysis of the class of drug showed that it doubled the risk of heart failure, regardless of whether or not the patients were considered at high risk before they took the drug.
"Even if you restricted it to patients who don't have heart failure, you will still get patients who newly develop heart failure as a result of Avandia," Dr Loke said.
He has calculated that annually in the UK patients could suffer "about 1,000 extra heart attacks and possibly 600 extra cases of heart failure too as a result of using Avandia".
Launched in Europe 10 years ago, Avandia quickly became the market-leading diabetes tablet, earning GSK billions of pounds.
Usha Patel has diabetes and used the drug to manage her condition. But when she developed painful conditions including swelling in her legs and further tests showed that she had developed heart problems, her GP advised her to stop taking Avandia.
"Because of your heart problems, we don't want you to take any more tablets," her GP told her. "Stop it the next day. Don't take it any more."
'First priority' Other patients Panorama spoke to have had a more positive experience with their Avandia prescription.
Helen Lovatt was first prescribed the drug by her GP six years ago and thinks that, together with her recent weight loss, it has helped bring her diabetes under control.
"It suits me, doesn't upset me in any way so if it's not broken why mend it?
"I saw in the paper about the possible side effects, but if my doctor's keeping a good check on me, I'm not going to sit and worry about it," she said.
In response to Panorama's findings, GSK said: "Patient safety is our first priority.
"We have carried out an extensive research programme, involving more than 50,000 patients to analyse the safety and benefits of Avandia and continue to believe it is safe and effective when it is prescribed appropriately."
The Europe-wide review by the European Medicines Agency into Avandia will announce findings whether to restrict its prescription or withdraw it completely later this month.
Panorama: A Risk Worth Taking? is broadcast on BBC One, Monday 6 September at 2030 BST.
Source : BBC News 5/9/2010
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Avandia trial "risky", group claims
An ongoing trial of GlaxoSmithKline's Avandia puts patients' lives at risk and should be stopped immediately, a US pressure group has claimed.
Public Citizen said the diabetes drug, which has been investigated by the Food and Drug Administration (FDA) in the past over allegations it increased the risk of heart attack and chest pain, had an "unfavourable" risk profile and it urged the regulator to bring an end to the test.
Major concerns about Avandia were first raised in 2007. An FDA investigation of the treatment at the time noted its safety risks but decided to keep in on the market.
A later probe into the drug called for a "black box" warning on the product's packaging after a review of 42 studies linked it to an increased likelihood of heart problems.
FDA officials are believed to be taking a closer look at Avandia ahead of their scheduled summer meeting.
A spokesman for Glaxo said the company stood by the treatment.
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Ongoing review of Avandia and cardiovascular safety
The U.S. Food and Drug Administration (FDA) is reviewing data, submitted in August 2009, from a large, long-term clinical study on possible cardiovascular risks with the diabetes drug, Avandia (rosiglitazone).
FDA previously communicated to the public about the possible association between rosiglitazone and increased cardiovascular risk in a2007 safety alert. The agency also sought advice from external experts at the July 30th 2007 joint meeting of the FDA Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees. The RECORD study data represent the only new information from a completed randomized, controlled clinical trial of rosiglitazone received by FDA since the 2007 announcements.
The RECORD study was part of a post-approval commitment between the European Medicines Agency (EMA) and the manufacturer. The study was designed to evaluate cardiovascular safety outcomes in 2,220 patients with type 2 diabetes taking rosiglitazone plus metformin or a sulfonylurea compared to 2,227 patients taking metformin and a sulfonylurea. The RECORD study findings were published in the June 2009 issue of Lancet1.
Patients in the study were followed on average 5.5 years and were monitored for the occurrence of the primary endpoint (cardiovascular death and cardiovascular hospitalizations). There were several secondary endpoints including the composite endpoint for major cardiovascular events (cardiovascular death, heart attack or stroke). All cardiovascular endpoints were determined by a team of cardiologists who were unaware of which patients were receiving rosiglitazone.
The study reported no statistically difference in the primary endpoint in the rosiglitazone group compared to combined use of metformin and a sulfonylurea. In addition, there was no significant treatment difference in any of the secondary composite endpoints except for an increase in heart failure, which is a well-known side effect of drugs in this class, including Actos (pioglitazone). The increase in risk of heart failure is consistent with the warnings contained in the current drug label.
FDA is now reviewing the primary data from the completed RECORD study, conducting follow-up audits, and reviewing additional studies. This work is ongoing and no new conclusions or recommendations about the use of rosiglitazone in the treatment of type 2 diabetes have been made at this time.
In addition to the RECORD study, a number of observational studies of the cardiovascular safety of rosiglitazone have been published. FDA has been reviewing these on an ongoing basis.
The RECORD study was designed to evaluate the cardiovascular safety of rosiglitazone, which is consistent with FDA's December 2008 Guidance for Industry recommending that manufacturers of new treatments for diabetes carefully design their clinical trials to include an evaluation of cardiovascular safety. The RECORD study will be evaluated in the context of this recent Guidance.
Once FDA completes its review of the data from the RECORD study, the agency will present the totality of new and existing cardiovascular safety data on rosiglitazone at a public Advisory Committee meeting in July 2010. At that meeting, the Advisory Committee will provide an updated assessment of the risks and benefits of rosiglitazone in the treatment of type 2 diabetes.
At this time, FDA recommends that healthcare professionals:
- Follow the recommendations in the drug label when prescribing rosiglitazone. This includes a Boxed Warning stating that:
- Use of rosiglitazone in patients with established NYHA Class III or IV heart failure is contraindicated.
- Rosiglitazone is not recommended in patients with symptomatic heart failure.
- Rosiglitazone causes or exacerbates congestive heart failure in some patients, therefore healthcare professionals should monitor for the signs and symptoms of heart failure after starting treatment and after dose increases of rosiglitazone. If heart failure signs and symptoms occur, the heart failure should be managed appropriately and discontinuation or dose reduction of rosiglitazone must be considered.
- Available data on rosiglitazone and risk of myocardial ischemia are inconclusive. A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared rosiglitazone to placebo, found an association between rosiglitazone use and an increased risk of myocardial ischemic events such as angina or heart attack. Three other studies (mean duration 41 months; 14,067 total patients), comparing rosiglitazone to other oral diabetes medications or placebo, have not confirmed or excluded this risk. The recently completed RECORD study, currently being reviewed by FDA, is one of these three studies.
- Discuss with patients the risks of rosiglitazone, taking into account the clinical utility of rosiglitazone, the risks/benefits of other antidiabetic medications, and the risks associated with poorly controlled blood glucose.
- Discuss with patients the importance of adhering to their diabetes medication regimen.
- Report any adverse events associated with the use of rosiglitazone to FDA's MedWatch program at www.fda.gov/medwatch.
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GSK Knew Avandia's Risks for Years
A Senate report said Saturday that drug maker GlaxoSmithKline knew of possible heart attack risks tied to Avandia, its diabetes medication, years before such evidence became public.
The report was released on the heels of an article in The New York Times saying that confidential government reports show diabetes patients would suffer 500 fewer heart attacks and 300 fewer cases of heart congestion each month if they took a similar pill named Actos instead of Avandia.
Sen. Max Baucus, chairman of the Senate Finance Committee, and Chuck Grassley, the committee's ranking Republican, released the report, which follows a two-year inquiry, on Saturday. They are also asking the U.S. Food and Drug Administration why it allowed a clinical trial of Avandia to continue even after the agency estimated that the drug caused 83,000 heart attacks between 1999 and 2007.
Read the Finance Committee Report
CBS News Medical Correspondent Dr. Jennifer Ashton told CBS Radio News that the risks associated with the drug aren't exactly new.
"It should be re-emphasized that in 2007 the FDA issued a black-box warning against Avandia for an increased risk of heart attack and congestive heart failure," Ashton said, "so it's not new that patients who are on this drug or this class of drug should have very involved discussions with their health-care provider about their risks verses the benefits when it comes to taking those medications."
GlaxoSmithKline said in a statement the drug is safe. It said the committee report took data out of context from analyses of Avandia.
In 2007, the FDA ordered a warning to be included on Avandia's label warning that it might increase the risk of heart attacks. But the label also says data on the risks are inconclusive.
CBS NEWS HEALTH
20 February 2010
Staff Report on Glaxosmithkline And The Diabetes Drug Avandia
Four More Deaths Associated with Diabetes Drug Byetta
Lilly and Amylin Pharmaceuticals are saying there have been four deaths among patients with pancreatitis who took their Byetta diabetes drug, in addition to the two deaths reported last week by the FDA. Amylin says the four cases were not captured by the FDA, which received six reports of patients who developed hemorrhagic or necrotizing pancreatitis that required hospitalization. Two of those died. The additional four cases reported today did not involve patients with the necrotizing form of the disease, which affects 15 percent to 20 percent of patients with inflammation of the pancreas.
“It appears the FDA focused on necrotizing and hemorrhagic pancreatitis, whereas these other four cases only had pancreatitis in their history,” Orville Kolterman, Amylin’s senior vice president of research and development, tells Reuters.
In the necrotizing form of pancreatitis, enzymes digest the pancreas, which can lead to a hemorrhage. However, Kolterman says the deaths were not considered related to the pancreatitis. Even so, he said the company was reporting them “in the interests of transparency.”
The prescribing information for Byetta, which has been taken by an estimated 1 million patients, was updated to include the risk of pancreatitis last October. The FDA cited 30 reports of pancreatitis in Byetta patients and said the drug was suspected in some cases. One of the four deaths reported on Tuesday was known at that time, Kolterman says.
News of the deaths that were reported by the FDA on Aug. 18 sent Amylin’s shares down 13 percent, and investors questioned the company’s failure to issue a news release or hold a conference call to discuss it. Now, Amylin says it is providing all info possible to ensure patients are not confused by what they read and that future cases of pancreatitis are not necessarily interpreted as being related to treatment with Byetta.
Kolterman adds they don’t expect any link to Byetta LAR, a once-weekly updated formulation that Wall Street is excited about. He says no cases of pancreatititis have been seen in patients being tested with the new version.
SOURCE Pharmalot (Aug 26th 2008)
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Diabetes Medication - Byetta (exenatide) + Renal Failure
FDA notified healthcare professionals of revisions to the prescribing information for Byetta (exenatide) to include information on post-marketing reports of altered kidney function, including acute renal failure and insufficiency. Byetta, an incretin-mimetic, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency), in patients using Byetta. Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems. Labeling changes include:
- Information regarding post-market reports of acute renal failure and insufficiency, highlighting that Byetta should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
- Recommendations to healthcare professionals that caution should be applied when initiating or increasing doses of Byetta from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).
- Recommendations that healthcare professionals monitor patients carefully for the development of kidney dysfunction, and evaluate the continued need for Byetta if kidney dysfunction is suspected while using the product.
- Information about kidney dysfunction in the patient Medication Guide to help patients understand the benefits and potential risks associated with Byetta.
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Experimental diabetes treatment Taspoglutide stopped due to high rate of adverse reactions
Roche Holding has stopped giving patients its experimental diabetes treatment taspoglutide in late stage clinical trials due to a high rate of adverse reactions, marking a major blow to drug once seen to have $2 billion a year potential.
The Swiss drugmaker said on Friday that the decision was based on a higher-than-expected rate of discontinuations due to gastrointestinal (GI) intolerability, and due to serious hypersensitivity reactions experienced by some patients, according to 52-week data from the trials.
"These discontinuation rates compromise interpretation of the long term safety data from the T-emerge studies, therefore continuing treatment with the current taspoglutide formulation is not considered to be in the best interest of patients," Roche said in a statement.
Leerink Swann analyst Joshua Schimmer said in a research note that if Phase III dosing has been suspended "we believe that this is the final blow for what was perceived as a compound in trouble after the disappointing data on hypersensitivity and nausea/vomiting presented at the American Diabetes Association (meeting) this year."
The drug, given once weekly by injection, suffered a serious setback in June after reports surfaced that there were cases of patients suffering hypersensitivity reactions to the medicine in clinical trials.
The latest blow to Roche is seen as a boon to Amylin Pharmaceuticals Inc and Eli Lilly and Co, which are awaiting a U.S. approval decision for their once-weekly injectable diabetes drug Bydureon.
Amylin shares closed up 1.9 percent, while Lilly shares finished up 0.8 percent.
Roche said it was not abandoning its drug, but was considering a reformulation of the medicine. Any reformulation would likely cause a significant delay beyond the one Roche signaled in June when the hypersensitivity data was revealed at the diabetes meeting.
At that time Roche said the setback would likely cause a delay in filing for approval of a minimum of 12 to 18 months. It had previously been aiming to apply for taspoglutide approval worldwide in 2011.
"Roche is assessing approaches to identify the root cause of the serious hypersensitivity reactions and to optimize the taspoglutide formulation to improve GI tolerability," Roche spokesman Terrence Hurley said.
"Upon review of options available, Roche will communicate about the next steps of the overall taspoglutide program by year end," he added.
"Amylin's Bydureon is expected to be the only weekly GLP-1 in the near-term," said ISI Group analyst Mark Schoenebaum in a research note. Schoenebaum was referring the class of drugs to which the Amylin/Lilly and Roche drugs belong.
Roche, which licensed taspoglutide from France-based Ipsen, once had high hopes for the drug. It had said in the past that taspoglutide could garner peak sales of at least 2 billion Swiss francs ($1.77 billion).
However analysts had already sharply lowered their sales projections for the drug following the previous clinical setbacks.
SOURCE : Reuters 10/9/2010
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Diabetes Drug Mediator/Benfluorex linked to 500 deaths in France
A diabetes drug called Mediator that had been used for decades - but was banned just a year ago over links to heart-valve damage - is now being linked by French authorities to some 500 deaths. Mediator, which is also known as benfluorex and was sold by Servier, was also used as an appetite supressant and had already been banned in the US, Spain and Italy.
“Our message to all those who took Mediator is that they must see a doctor, particularly those who took it for three months over the past four years,” Health Minister Xavier Bertrand told journalists in France after the French regulatory agency, Afssaps, issued its warning and recommendations (see this).
For its part, Servier rejected the estimated number of deaths as “theories founded on extrapolation” and argued that 2.5 percent of the population had valve trouble, adding that age and diabetes heightened the risk. “Simply observing a valve problem in a diabetic person does not allow it to be attributed to medicinal treatment which remains a very rare cause,” the drugmaker says in a statement (which apparently has not yet been placed on its web site). A Servier spokesman tells Agence France-Presse just four patients had lodged complaints about Mediator since 2009 and that 500 deaths represented a tiny risk compared to the number of people who took the drug. “But in terms of brand image, it’s disagreeable,” he adds.
Irene Frachon, a doctor who earlier this year published a study warning about the drug, told AFP that “Mediator is responsible for a health disaster…The health authorities were late in withdrawing this drug despite several alerts” about threats it posed to the heart valves. I know personally some of the victims and what they have suffered. Some of them have undergone open heart surgery and they have to take lots of medication.” She estimates 80 percent were women.
A similar Servier drug, the appetite-suppressor Isomeride, was withdrawn in 1997 after tests showed it raised the risk of high blood pressure, AFP writes. The drug spawned several lawsuits against Servier. Afssaps adds that 11 cases of valve damage in patients taking Isomeride were reported to drug safety authorities in France between 1997 and 2006. As it so happens, AFP notes that was the same year in which the confirmed case of heart valve damage caused by Mediator was confirmed.
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