Archive for the ‘Diabetes drugs’ Category

Inhaled insulin Exubera may cause lung cancer

Thursday, April 10th, 2008

Exubera insulinUS drugmakers Pfizer Inc and Nektar Therapeutics on Wednesday warned of cases of lung cancer in clinical trials of their inhaled insulin Exubera.

The findings led Nektar to announce it was abandoning its search for a new marketing partner for the troubled drug, effectively signaling Exubera’s demise after entering the market in January 2006.

Pfizer, the world’s largest pharmaceutical company, announced last October it stopped marketing Exubera, saying it did not meet customer needs or the financial expectations of the company.

The rise in lung cancer apparently linked to Exubera led Pfizer to update the medication’s warning label to include information “about lung cancer cases observed in patients who used Exubera,” the company reported in a statement.

It said that over the course of the clinical trial, six out of 4,740 Exubera-treated patients developed lung cancer, versus one of the 4,292 patients not treated with Exubera.

An additional case of lung cancer in an Exubera-treated patient was discovered after the drug’s debut on the market following its approval by the US Food and Drug Administration.

The updated label states that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were “too few cases to determine whether the development of lung cancer is related to the use of Exubera.”

“Some patients continue to take Exubera, including those enrolled in extended transition programs or clinical trials,” Pfizer chief medical officer Joe Feczko said in the statement.

“We are working closely with patients and their physicians to ensure the continued orderly transition from Exubera to alternative therapies,” he added.

Nektar announced it was stopping all spending on the drug, including research and marketing.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Nektar president Howard Robin on the company’s website.

Diabetes affects 230 million people worldwide, including 21 million in the United States, according to Pfizer. Exubera is a short-acting insulin breathed in through an inhaler that helps control high blood sugar in people with diabetes.

Pfizer warns Exubera patients about risk

Pfizer Inc. said Wednesday it is warning patients using its inhaled insulin product Exubera about the risk of lung cancer, leading Nektar Therapeutics to terminate its inhaled insulin programs.

Nektar had been Pfizer’s partner on Exubera from 1995 until Pfizer discontinued the drug in October 2007 after lackluster sales. Some patients continue to take the drug, however, including some enrolled in extended transition programs or clinical trials.

On Wednesday, Pfizer said it updated the U.S. product labeling for Exubera Inhalation Powder to include a warning about lung cancer cases observed in patients who used the inhaled insulin treatment.

Over the course of Exubera’s clinical trial program, 6 of the 4,740 patients treated with Exubera developed lung cancer, compared with 1 of the 4,292 patients not treated with the drug.

There was also a post-marketing report of lung cancer in one Exubera-treated patient.

The label notes that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were too few cases to determine whether the cancer is related to use of Exubera.

Pfizer said the data was reviewed by the company and the Food and Drug Administration.

Nektar said it will stop all spending associated with its inhaled insulin programs and will not incur any additional charges related to the action.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Howard W. Robin, president and chief executive of Nektar, in a statement. “Fortunately, over the past year Nektar has significantly transformed its business, moving away from inhaled insulin.”

Exubera

Generic Name: insulin inhalation
Brand Names: Exubera

What is Exubera?

Insulin inhalation (Exubera) was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal.

Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the blood.

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Galvus (vildagliptin) improves glucose control

Thursday, February 21st, 2008

GalvusFor people with type 2 diabetes and moderately elevated blood glucose levels, the medication vildagliptin, sold under the brand name Galvus, can produce long-term improvements in the functioning of the insulin-secreting beta cells in the pancreas along with better glucose control, researchers report.

“Improvement of glucose control, which was a known fact for vildagliptin, is paralleled, and likely caused, by an improvement of beta-cell function,” Dr. Andrea Mari told Reuters Health.

Mari, from the National Research Council, Padova, Italy, and colleagues put 306 patients with type 2 diabetes on vildagliptin or an inactive placebo for a year. The participants had an A1C in the range of 6.2 percent to 7.5 percent, indicating only mild hyperglycemia.

Vildagliptin significantly increased the secretion rate of insulin by 17 percent compared to placebo, the investigators report in the Journal of Clinical Endocrinology & Metabolism.

The spike in glucose levels after a meal improved for patients on vildagliptin treatment but worsened somewhat for those given placebo, as did A1C levels, the researchers found.

The improvements with vildagliptin were fully apparent within 24 weeks of treatment, the investigators say, but none of the effects on beta-cell function remained after 4 weeks once the medication was stopped.

Because of this, Mari’s team concludes that longer studies are needed to see if vildagliptin modifies the progression of type 2 diabetes.

About Galvus

In clinical studies, Galvus has demonstrated significant reductions in blood sugar for one year. Galvus is suitable for once-daily dosing and has been evaluated both as monotherapy and in combination with other anti-diabetes agents. Galvus was not associated with overall weight gain, a key benefit for people with diabetes who struggle to keep their weight under control. The overall incidence of side effects with Galvus including hypoglycemia (excessively low blood sugar) and edema (fluid retention) was similar to placebo. Galvus lowers blood sugar by targeting islet dysfunction, i.e., it improves the ability of the islet’s alpha- and beta-cells to appropriately sense and respond to sugar in the blood.

Metformin is effective in reversing weight gain

Sunday, January 20th, 2008

MetforminTreatment with metformin or lifestyle changes promoting exercise and a healthy diet are both effective in reversing the weight gain associated with antipsychotic medications, according to a clinical trial conducted in China. However, a combination of the two approaches is even better.

Metformin, sold under various trade names such as Glucophage, is primarily used to lower blood sugar in patients with type 2 diabetes.

Dr. Jing-Ping Zhao and associates at the Mental Health Institute of the Second Xiangya Hospital in Changsha note that by lowering glucose production in the liver, metformin prevents weight gain and decreases insulin resistance.

However, its effect on the metabolic complications of antipsychotic medication has not been established, the researchers point out in the Journal of the American Medical Association.

Zhao’s group enrolled 128 adults with schizophrenia who gained more than 10 percent of their body weight after taking an antipsychotic drug for 1 year. They were randomly assigned to receive metformin, placebo, lifestyle interventions plus metformin, or lifestyle interventions plus placebo.

The lifestyle intervention included an educational program, the American Heart Association’s step 2 diet and daily moderate exercise for at least 30 minutes.

“To keep patients with schizophrenia compliant with treatment, they all had to be under the care of their parents or another adult caregiver,” Zhao told Reuters Health.

The subject’s average body mass index was 24.5 at the beginning of the study and the average weight was 64.6 kg (142.4 lbs).Body mass index (BMI) is the ratio of height to weight commonly used to classify individuals as underweight, overweight or in a normal weight range. A BMI of 24.5 is at the top end of the normal range.

After 12 weeks, all measured outcomes had worsened in the placebo group, including a weight gain of 3.1 kg (6.8 lbs).

In the metformin group, all outcomes had improved; subjects lost an average of 3.2 kg (7.1 lbs). Subjects in the lifestyle intervention group lost 1.4 kg (3.1 lbs).

However, the benefits of combined treatment were significantly greater than those achieved by either intervention alone. Weight loss in the combined treatment group averaged 4.7 kg (10.4 lbs).

“We recommend that lifestyle intervention plus metformin be considered first for those with weight gain. If patients cannot tolerate or adhere poorly to lifestyle intervention, they should consider metformin alone,” Zhao advised.

“Of course, the safety of metformin must be ensured,” Zhao stressed.

The team is currently engaged in the next stage of their research, he added. “We are studying the efficacy of long-term metformin and lifestyle intervention, and different doses of metformin, on antipsychotic-induced weight gain.”

Diabetes Drug May Cut Med-Related Weight Gain

Improved diet, more exercise and the diabetes medication metformin can help people suffering with schizophrenia control the weight gain that typically accompanies their medications, a Chinese study suggests.

Three months of both medication and lifestyle change resulted in a loss of two centimeters around the waist as well as improvement in other health measures, such as insulin resistance, the researchers report in the Jan. 9/16 issue of the Journal of the American Medical Association.

Metformin is typically prescribed to help control blood sugar levels in people with diabetes. Previous research has shown that metformin can prevent weight gain in people with diabetes and may help manage weight in some overweight people.

Doctors prescribe atypical antipsychotic (AAP) medications to manage a variety of psychotic disorder and behavioral disturbances, including schizophrenia. However, the drugs often also affect the body’s metabolism, resulting in unhealthy cholesterol levels, weight gain and glucose intolerance.

A team based at the Mental Health Institute of the Second Xiangva Hospital, Central South University, China, tested the effect of metformin and lifestyle changes, together and separately, on the weight and insulin levels of 128 adults with schizophrenia. All the participants had gained at least 10 percent of their body weight after starting antipsychotic medications.

The participants were randomly assigned to one of four groups for 12 weeks, while continuing their medication: One group received a placebo or sugar pill; the second one received 750 milligrams per day of metformin; the third received 750 milligrams per day of metformin with lifestyle intervention; and the fourth went through the lifestyle intervention alone. The lifestyle interventions included health education, diet and exercise.

An analysis of the data found that patients in the combination group and patients who took either metformin or engaged in lifestyle change all reduced their weight, body-mass index (a measure of height and weight), waist circumference, insulin levels and insulin resistance.

The participants who took metformin and changed their diet and exercise saw a decrease of 1.8 in their body-mass index, 3.6 in insulin resistance and lost two centimeters in waist circumference. Metformin alone resulted in an average loss of 1.2 in body-mass index, 3.5 in insulin resistance and 1.3 centimeters from the waist. Those who only exercised and changed their diet saw a loss of 0.5 in body-mass index and 1.0 in insulin resistance, but they were no slimmer at the waist. People who took the placebo continued to increase in body mass, waist and insulin resistance, said the researchers.

Metformin

Brand Names: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet

What is metformin?

Metformin is an oral diabetes medicine that helps control blood sugar levels.

Metformin is for people with type 2 (non-insulin-dependent) diabetes.

Metformin is sometimes used in combination with insulin or other medications, but it is not for treating type 1 diabetes.

Metformin may also be used for purposes other than those listed in this medication guide.
What is the most important information I should know about metformin?
Do not use metformin if you have kidney disease, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

Before taking metformin, tell your doctor if you have liver disease or a history of heart disease.
Some people have developed a life-threatening condition called lactic acidosis while taking metformin. Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting.

If you need to have any type of x-ray or CT scan using a dye that is injected into a vein, you may need to temporarily stop taking metformin. Be sure the doctor knows ahead of time that you are using metformin.
Know the signs of low blood sugar (hypoglycemia) and how to recognize them, including hunger, headache, confusion, irritability, drowsiness, weakness, dizziness, tremors, sweating, fast heartbeat, seizure (convulsions), fainting, or coma (severe hypoglycemia can be fatal). Always keep a source of sugar available in case you have symptoms of low blood sugar.

What should I avoid while taking metformin?

Avoid drinking alcohol while taking metformin. Alcohol lowers blood sugar and may increase the risk of lactic acidosis while you are taking this medicine.

Metformin side effects
Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting. Stop using metformin and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling short of breath, even with mild exertion;
  • swelling or rapid weight gain; or
  • fever, chills, body aches, flu symptoms.

Less serious side effects may include:

  • headache or muscle pain;
  • weakness; or
  • mild nausesa, vomiting, diarrhea, gas, stomach pain.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.

Avandia heart risks

Wednesday, December 12th, 2007

Avandia risksThe findings of clinical trials have linked the use of thiazolidinediones, a class of diabetes drugs, with congestive heart failure and possibly heart attacks. Now, new research indicates that these associations, at least with Avandia, also apply to individuals in the community, and not just clinical trials.

Dr. Lorraine L. Lipscombe, from the Institute for Clinical Evaluative Sciences in Toronto, and colleagues analyzed data for 159,026 older adults who were treated with at least one oral diabetes drug between 2002 and 2005 and were entered in an Ontario healthcare database. The subjects were followed through March 2006.

During an average follow-up period of 3.8 years, 7.9 percent of the patients were hospitalized for congestive heart failure, 7.9 percent were hospitalized for a heart attack, and 19 percent died, according to the researchers’ report in Journal of the American Medical Association.

Current thiazolidinediones use increased the risks of heart failure, heart attack and death by 60 percent, 40 percent, and 29 percent, respectively, compared with the use of other types of oral diabetes drugs.

Further analysis revealed that the risks were largely confined to patients who were using Avandia, known generically as rosiglitazone.

“These findings provide evidence from a real-world setting and support data from clinical trials that the harms of thiazolidinediones may outweigh their benefits, even in patients without obvious…cardiovascular disease,” the authors write.

More studies are needed to better define the risk-benefit ratio and the trade-offs associated with thiazolidinedione therapy and to explore if the treatment risks are confined specifically to rosiglitazone.

Avandia risks highlighted

Canadian researchers furnished the strongest evidence to date linking the popular diabetes drug Avandia to an increased risk of heart attack in a scientific study released yesterday.

Compared with other diabetes pills, Avandia’s use was associated with a 60 percent higher risk of heart failure, 40 percent higher risk of heart attack and 30 percent higher risk of death in patients 65 and older, the researchers found.

“The risks associated with these drugs may outweigh the benefits, at least for older populations,” said Dr. Lorraine L. Lipscombe, the lead author of the study and a researcher at a health research agency funded by the Ontario government.

The findings, published in the influential Journal of the American Medical Association, will probably intensify pressure on the government to restrict sales of the oral diabetes medicine.

“It should come off the market,” said Dr. Sidney M. Wolfe, director of health research at Public Citizen, a liberal interest group preparing to petition the Food and Drug Administration to pull the drug.

Sales of Avandia have plummeted since Dr. Steven Nissen, a prominent cardiologist, reported in May that it raised the risk of heart attack. His report prompted congressional hearings and demands to stop sales.

The FDA decided against that last month, instead adding a label warning that urges users to consult a doctor if they have serious heart problems.

The decision divided agency staff. Ultimately, FDA officials decided the scientific evidence wasn’t conclusive, and they asked Avandia’s manufacturer to conduct a long-term study.

In a statement, the FDA said it would review the results from the Canadian study, but it needs more evidence before taking any further action. “This new study we have just seen today does not change FDA’s recommendations,” the agency said.

GlaxoSmithKline, Avandia’s maker, dismissed the Canadians’ findings as limited and misleading because the elderly studied might have been at higher risk of heart problems.

The Philadelphia company, which is conducting a long-term study of Avandia’s side effects, said in a statement that many other studies show Avandia is safe and effective.

The new study is the first to review side effects in real patients, rather than test subjects, according to Lipscombe, a researcher at the Institute for Clinical Evaluative Sciences in Toronto.

Beginning in March, Lipscombe and her colleagues analyzed health care records for all elderly Ontario residents who took an oral diabetes medicine between 2002 and 2006.

Lipscombe said they focused on the elderly because 40 percent of diabetes patients in Ontario are 65 and older, but the elderly tend to be underrepresented in scientific drug studies.

The researchers didn’t find a higher heart risk among users of Actos, an Avandia competitor that belongs to the same class of diabetes drugs, but Lipscombe said there weren’t enough Actos users to draw a firm conclusion.

Older Diabetics Using Avandia Face Increased Death Risk

Older patients using the diabetes drug Avandia faced an increased risk of heart attack, heart failure and even death, new research shows.

According to the Canadian authors of the study, which is published in the Dec. 12 issue of the Journal of the American Medical Association, this is the first population-based look at the class of drugs to which Avandia belongs and the first report to find an increase in mortality rates.

“Our study looked at an older population in the real world who tend to be underrepresented in research trials and are at higher risk,” said study author Dr. Lorraine L. Lipscombe, a researcher with the Institute for Clinical Evaluative Sciences in Toronto. “While the overall risk versus benefit is difficult to interpret in all people, in older people, the risks may outweigh the benefit.”

“This is very striking data,” added Dr. Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation. “This and other studies are going to put tremendous pressure on the FDA [U.S. Food and Drug Administration] to act more forcefully with regard to Avandia.”

But the maker of Avandia (rosiglitazone), GlaxoSmithKline, took issue with the findings.

In a prepared statement, the company said the Canadian study “has significant limitations and generates misleading conclusions regarding acute myocardial infarction and death. These conclusions are inconsistent with a more robust body of evidence from large, long-term, prospective, well-designed clinical studies, including ADOPT and RECORD. These long-term trials in diabetic patients comparing rosiglitazone 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 thiazolidinedione (TZDs).”

Nissen was the first scientist to publish concerns about Avandia and increased heart risks in a study last May.

After that and other research was released, the FDA added a “black box” warning to all drugs in the class. An FDA advisory panel voted against removing the drug from the market, citing inconclusive evidence.

The Canadian label for Avandia carries a stronger message: The drug is not to be used as the sole medication for type 2 diabetes unless the patient cannot take another drug to lower blood sugar and that the drug should not be used by any patient with heart failure.

People with type 2 diabetes are already at heightened risk for cardiovascular disease.

Thiazolidinediones including Avandia and Actos (pioglitazone) heighten the body’s sensitivity to insulin. Some 3.5 million U.S. patients take Avandia, which has also been linked to bone loss in some patients.

The current study involved an older (66 and over), “real-world” population consisting of more than 159,000 residents of Ontario in this age group who were treated with at least one oral diabetic medication. The patients were followed for about four years.

Compared to individuals taking more than one oral hypoglycemic agent, people using Avandia on its own had a 60 percent increased risk of congestive heart failure, a 40 percent increased risk of heart attack, and a 29 percent increased risk of dying.

The increased risks were associated with Avandia only, but fewer people in the study took Actos, so the results could be skewed, the researchers noted.

“It looks like the results were limited to Avandia, but 50 percent fewer people were on Actos, so you can’t rule out an increased or decreased risk with Actos,” Lipscombe said. “We need more studies.”

“It’s an observational study and, like all observational studies, this has strengths and weaknesses. These studies do not provide the strength of evidence of a prospective, randomized trial,” Nissen pointed out. “But as observational studies go, this one is very helpful, because it is quite large, and it is independent, not sponsored by any company. Remarkably, with Avandia, the increased risk of heart attack is very similar to what we reported in our meta-analysis last May.”

In related research appearing in the same issue of JAMA, a review of 25 studies found that current smokers have a 44 percent increased risk of developing type 2 diabetes compared with nonsmokers.

The degree of risk was linked to the level of smoking — there was a 61 percent increased risk for those smoking 20 or more cigarettes a day and a 29 percent increased risk for those who smoked less, said the Swiss researchers. Former smokers had a 23 percent increased risk.