Nissen would later pool the data from both the DREAM and ADOPT trial, as well as a number of smaller trials, to show Avandia was consistently associated with an increased incidence of adverse cardiovascular events even if no single trial reached statistical significance. Also concerning, there was a higher incidence of fractures associated with Avandia in women though, quite peculiarly, not in men.
Following the discovery that Avandia may increase the risk of fractures in women, the FDA asked Takeda Pharmaceuticals, the maker of Actos the other TZD , to investigate the rate of fractures in patients taking Actos.
Takeda issued the so called "Takeda Letter" that indicated that, like Avandia, Actos increased bone fracture rate in women, particularly in the lower and upper limbs. The increased risk of fracture for both drugs appears to start after about one year of treatment. The concerns about the cardiovascular risks of Avandia left a dark cloud over Actos. Both drugs have similar efficacy in controlling blood glucose and generally have the same side effects including fluid retention, leading to swelling and weight gain.
However, one intriguing difference between Actos and Avandia is their effect on lipid profiles. Avandia increases LDL cholesterol the bad cholesterol and increases triglycerides, while Actos has the opposite effect. If Avandia's effects on lipids are causing the potential increase in cardiovascular risk, then Actos would not be expected to share this risk.
Nissen published another pooled analysis indicating that unlike Avandia, Actos is not associated with increased heart attack risk. This was particularly significant given that it was Dr. Nissen who originally sparked fears about Avandia. Nissen believes that the difference between Avandia and Actos is due to their difference on lipids.
Nissen and others maintain that Actos and Avandia are completely different drugs and should not be considered equals. Many disagree both with Dr. Nissen's analysis and his conclusions. As the maker of Avandia and others contend, there are no head-to-head comparisons of Actos and Avandia, and it is very difficult to compare their respective risks. It is conceivable that Actos and Avandia actually have identical risks. Nissen's analysis of pioglitazone was based on a relatively small number of studies, and a single study - the PROactive study - contributed most of the data, and the patients in this trial were at a high risk of cardiovascular disease.
Controversy continues to surround Avandia and Actos. Some health care providers believe that only Avandia increases cardiovascular risk, some say both Avandia and Actos do; others argue that neither significantly increases cardiovascular risk - or that any risk is highly outweighed by the potential benefits. So if you have a history of bladder cancer, or have other risk factors for bladder cancer, you also may want to avoid the drugs.
Still, pioglitazone works so well in older patients that, in my judgment, the benefits outweigh the possible risks for most people. For the reasons mentioned above, if you take pioglitazone, you and your doctor or other health professional should carefully watch for signs or symptoms of heart failure.
These include shortness of breath dyspnea when you exert yourself or when you lie down, sudden weight gain, or swelling in your legs, ankles and feet. This is especially important when you start taking the drug and whenever there is a change in dosage.
Your physician or other health professional should see you on at least a monthly basis until your optimal dose is reached, and after that evaluate your hemoglobin A1c and physical condition at day intervals. Patients who take pioglitazone also should do a couple of simple self-checks every day. The first is to press a finger into one of their ankles and make sure that there's no indentation left behind when they lift it.
If the indentation remains, it's a sign of edema. The second is to make sure they're able to breathe freely when lying down without having to use a pillow to elevate their head. If they should experience trouble breathing, they should get to an emergency room right away.
Fnally, it's important to remember that older patients do not need to keep their blood glucose levels quite as low as younger patients need to. While the American Geriatrics Society recommends that "a reasonable goal for A1c in relatively healthy adults with good functional status is 7 percent or lower," I find that an appropriate target for older people is 7 or to 9 percent.
Although metformin — either alone or with glipizide or glimepiride — is often cited as the treatment of choice for people with type 2 diabetes, it's nearly always the wrong treatment for older patients, who typically lack the ability to flush the drugs out of their kidneys before they accumulate at toxic levels. Because pioglitazone is metabolized in the liver, not the kidneys, it's typically the best way to control type 2 diabetes in older patients.
Ask the Pharmacist is written by Armon B. Neel Jr. Remember to go to the AARP home page every day for tips on keeping healthy and sharp, and great deals. Information contained in the Ask the Pharmacist column by Dr. Armon B. June — France announced discontinued Actos prescriptions and sales as a result of data gathered in an Actos study conducted by the French Medicines Agency from to , which revealed a strong link between Actos and the development of bladder cancer. The FDA warning mentioned that when Actos is taken for more than 12 months, there is an increased risk of developing bladder cancer.
The FDA demanded the Actos label be updated with information about the bladder cancer risks. July 12, — Takeda Pharmaceuticals issued an Actos recall in France. July 21, — The European Medicines Agency ruled to keep Actos on the drug market, but made a recommendation that healthcare providers closely monitor patients taking Actos for any signs of bladder cancer.
The EMA also recommended that a thorough screening process be established when considering prescribing Actos to new patients. August 4, — The FDA approved new warning label information about the risk of developing bladder cancer while taking Actos. September — The first Actos class action lawsuit is filed in Louisiana.
0コメント