Metabolic effects of a conversion from rosiglitazone to pioglitazone in Native American patients with type 2 diabetes

Jodi Sparkman, PharmD, Jeffrey Stroup, PharmD, BCPS, Ryan Schupbach, PharmD, BCPS, and Ryan Carnahan, PharmD, MS, BCPP

In this retrospective electronic chart review, we evaluated the metabolic changes that occurred in Native American patients with type 2 diabetes who were treated with rosiglitazone and then converted to pioglitazone with no other changes in medication regimens for diabetes or dyslipidemia. Thirty-four patients were included in the analysis. After the conversion from rosiglitazone to pioglitazone, significant decreases in the levels of total cholesterol (10.1%), low-density lipoprotein cholesterol (11.7%), and triglycerides (15.3%) were seen. No significant changes occurred in weight, body mass index, fasting glucose, hemoglobin A1c, high-density lipoprotein cholesterol, blood pressure, or liver function tests. Significantly more patients achieved low-density lipoprotein cholesterol and triglyceride target goals when taking pioglitazone than when taking rosiglitazone. No drug discontinuations or adverse effects were reported among the evaluable population. These results are consistent with results of other studies evaluating these two drug therapies.

AHA: More Evidence Against Broad Cardiovascular Risk with Pioglitazone

ORLANDO, Nov. 9 -- Pioglitazone (Actos) appeared, at worst, neutral for cardiovascular risk, except heart failure, in yet another meta-analysis examining thiazolidinedione safety.
Action Points
Explain to interested patients that the thiazolidinediones pioglitazone and rosiglitazone do appear to carry a risk of heart failure, but this study supports that other cardiovascular risks may be different between the two.
Note that this study was published as an abstract and presented orally at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
Pioglitazone did not increase risk of MI, stroke, revascularization, death, or various combinations thereof, according to the five-trial meta-analysis reported here at the American Heart Association meeting.
But neither did it significantly reduce risk aside from unstable coronary syndromes (P=0.039) and stroke and MI combined (P=0.024), reported Nagapradeep Nagajothi, M.D., of the Rosalind Franklin University of Medicine and Science in North Chicago, Ill., and colleagues.
Nevertheless, they concluded that their findings supported those of a much larger but less specific meta-analysis that appeared in the September issue of the Journal of the American Medical Association.
The JAMA analysis suggested an 18% reduction in risk of MI, stroke, or death with the drug (P=0.02). (See: Ups and Downs of Thiazolidinediones for Diabetes Assessed by Dueling Meta-Analyses)
"These are two comparable studies that show similar results," Dr. Nagajothi said.
But despite the researchers' enthusiasm, the results were suggestive rather than confirmatory.
The meta-analysis included five randomized controlled trials with a total of 9,965 patients in which MI outcomes were reported for pioglitazone monotherapy.
The comparison drug was metformin or gliclazide in one trial, glyburide in another, and glimepiride (Amaryl) in a third. Two trials used placebo as the comparator arm. Study duration ranged from six to 34.5 months.
Comparing pioglitazone with controls, the findings included:
MI risk was 14% lower, though not significantly so (hazard ratio: 0.86, 95% confidence interval: 0.69 to 1.07, P=0.17).
Stroke risk was 21% lower with a trend for significance (HR: 0.79, 95% CI: 0.61 to 1.02, P=0.07).
Revascularization risk was 60% lower but still not significant (HR: 0.4, 95% CI: 0.13 to 1.23, P=0.11).
All-cause mortality was similar between treatment groups (HR: 0.94, 95% CI: 0.78 to 1.15, P=0.56).
The combined endpoint of stroke, MI, revascularization, and death was 37% lower (HR: 0.63, 95% CI: 0.376 to 1.06, P=0.08).
MI and unstable angina together were significantly reduced (HR: 0.83, 95% CI: 0.68 to 0.99, P=0.039).
Stroke and MI together were significantly reduced as well (HR: 0.83, 95% CI: 0.71 to 0.98, P=0.024).
The flurry of cardiovascular risk studies sparked by a meta-analysis in the New England Journal of Medicine that suggested rosiglitazone (Avandia) increased MI risk by 43% have consistently found an increased risk of heart failure, so the researchers did not look at that outcome.
However, the heart failure risk for pioglitazone may be related to fluid retention rather than damage to the heart muscle itself, other researchers have suggested. The differences seen in cardiovascular risk between the drugs suggest that there is not a class effect, which might be explained by pioglitazone's relatively more favorable effects on lipids, Dr. Nagajothi said.
"Thiazolidinediones turn on or off more than 100 genes each, which are not identical," he added.
The researchers reported no conflicts of interest.
Primary source: American Heart Association meetingSource reference: Nagajothi N, et al "Pioglitazone and cardiovascular outcomes" AHA meeting 2007; Abstract 3732.

AHA: Doctors Dispute 'Bad News' About Thiazolidinediones

By Ed Susman, Contributing Writer, MedPage TodayNovember 06, 2007
ORLANDO, Nov, 6 -- Media hysteria rather than hard science resulted in black box warnings on supposed dangers of thiazolidinediones for treatment of patients with diabetes, some doctors here suggested.
In an industry-sponsored symposium held in conjunction with the American Heart Association meeting, Burton Sobel, M.D., of the University of Vermont in Burlington, noted that the drugs -- specifically rosiglitazone (Avandia) and pioglitazone (Actos) -- have been at the center of a "maelstrom of controversy that has come about for whatever reason."
Particularly singled out for criticism was the recent meta-analysis authored by Steve Nissen, M.D., director of cardiology at the Cleveland Clinic (NEJM, May 21, 2007).
The validity of Dr. Nissen's findings was challenged by Silvio E. Inzucchi, M.D., clinical director of the Section of Endocrinology at Yale. "Any minor manipulations to this information can be done to show either how much harm rosiglitazone is doing, or how much good it has done," Dr. Inzucchi claimed.
He said that in the Nissen paper researchers "took results from small trials, calculated the odds and they came up with a 43% increase in myocardial infarction."
In a follow-up analysis, he said, researchers used the "faulty" Nissen data. "This is why they had a similar outcome," he said.
Dr. Inzucchi agreed there was some data that indicated rosiglitazone patients appeared to experience a "modest increase in heart failure." But, he said, the news accounts of these studies created an atmosphere that made it necessary for the Food and Drug Administration to require black box labeling for the drugs. "That label is an FDA reaction to the media hysteria surrounding thiazolidinediones," he said.
Another speaker at the symposium, sponsored by Takeda Pharmaceuticals, the developer of pioglitazone, William Chutkow, M.D., Ph.D., of Harvard and Brigham and Women's Hospital, reviewed data on drugs used in treatment of diabetes, including the thiazolidinediones. "[Thiazolidinediones] seem capable of improving all of the insults a diabetic patient would have to face," he said.
Although he discussed metformin, niacin, and other medications, Dr. Chutkow said, "there is still a lot of confusing data, even as late as the year 2007, out there about these drugs to figure out which amongst them is the 'safe' one."

This Time It's A Draw for Rosiglitazone (Avandia) and Pioglitazone (Actos)

BURLINGTON, Mass., Sept. 28 -- Pooled data from seven randomized trials of thiazolidinediones for type 2 diabetes confirmed a significant risk of congestive heart failure with either pioglitazone (Actos) or rosiglitazone (Avandia), but neither increased the risk of cardiovascular death.Compared with controls patients treated with either drug an a 72% increase in risk of congestive heart failure (RR 1.72, 95% CI 1.22-2.42, P=0.002), but the pooled risk for cardiovascular death was 0.91 (95% CI 0.63-1.32, P =0.063) with rosiglitazone and 1.01 (95% CI 0.51-2.01 P =0.98) with pioglitazone,
So found Rodrigo M. Lago, M.D., of the Lahey Clinic Medical Center here, and colleagues. They reported the data in the Sept. 29 issue of The Lancet.
"The pooled RR for development of congestive heart failure was 2.18 (95% CI 1.44 -3.32, P =0.0003) in the five trials of rosiglitazone, and 1.32 (1.04-1.68, P =0.02) in two studies with pioglitazone," they wrote.
The seven studies enrolled 20,191 patients who were followed for a mean of about 30 months. During that time 360 patients, including 214 who were given either rosiglitazone or pioglitazone, developed congestive heart failure. The congestive heart failure rate was 2.3% among patients treated with thiazolidinediones versus 1.4% for controls.
The estimated number-needed-to-harm for congestive heart failure was 107 across all seven studies but that number varied from 35 patients in one rosiglitazone trial to 491 to another rosiglitazone trial.
Absence of increased risk of cardiovascular mortality in the face of significant increase in the risk of congestive heart failure, suggests that thiazolidinedione-related fluid retention is more benign than other causes of heart failure, but the investigators said that hypothesis cannot be confirmed with a meta-analysis.
They noted that one trial initially found more heart failure and heart failure mortality for patients treated with pioglitazone, but subsequent analyses found that although more cases of heart failure were associated with pioglitazone than with controls, the number of primary and secondary events were similar in each group.
One interpretation of those data would be that pioglitazone-associated heart failure was indeed more benign that that caused by other factors, they wrote. But another, just as likely, interpretation was that "despite the potential for more adverse cardiovascular events associated with congestive heart failure, pioglitazone could have a cardioprotective effect compared with placebo."
The authors said their analysis was subject to all the limits of the meta-analysis methodology-reliance on aggregated data, varying definitions of heart failure, control groups that included both placebo and active treatments, and a lack of patient-specific outcome information.
Randomized trials of these two drugs is proving to be a mother-lode for data-mining researchers and this analyses is the latest in along line of meta-analyses, post-hoc analyses, and systemic reviews of the two drugs, most of which have been published in the four months since the New England Journal of Medicine published a meta-analysis of 42 trials by Cleveland Clinic investigators, which found a 43% increase in risk of myocardial infarction with rosiglitazone.
Earlier this month the Journal of the American Medical Association published a second rosiglitazone analysis that appeared to confirm the Cleveland Clinic paper along with a meta-analysis of pioglitazone studies that revealed an 18% reduction in cardiovascular mortality with pioglitazone.
A commentary and editorial in The Lancet offerred weary and wary advice about the interpreting the new paper by Dr. Lago and colleagues.
John G. F. Cleland, MD., and Stephen L. Atkin, M.D., of Castle Hill Hospital at the University of Hull in England, pointed out that although the analysis suggested that neither drug was associated with increased cardiovascular deaths "the confidence interval cannot exclude a 25% increase."
But the real problem-the elephant in the room-they wrote was that treatment should be "effective rather than merely innocuous." Both agents are most effective at improving glycemic control, but improved "glycemic control is not a surrogate for effective care of patients who have diabetes, which should be to reduce disability and increase lifespan."
The Lancet's editors pointed out shortcomings of meta-analyses. But they agreed that the reliance on surrogate markers-in this case hemoglobin A1C-"skirts the outcomes that matter most to patients-microvascular and macrovascular complications, quality of life, and survival."
The editors concluded with advice to the FDA and other regulatory agencies to demand better safety data or face the consequences, i.e. that "thiazolidinediones might simply become the latest in a series of preventable drug disasters."
Richard W. Nesto of the Lahey Clinic, senior author of the meta-analysis, disclosed financial support from GlaxoSmithKline and Takeda. No funding source was revealed for the study. Dr. Cleland disclosed support from the British Heart Foundation, GlaxoSmithKline, Roche, AstraZeneca, Pfizer, Sanofi, and Servier. Dr. Atkin disclosed support from GlaxoSmithKline, Takeda, and the British Heart Foundation. Primary source: The LancetSource reference: Lago RM "Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomized clinical trials." The Lancet 2007;370:1129-36
Cleland JGF and Atkin SL "Thiazolidinediones, deadly sins, surrogates, and elephants" The Lancet 2007; 370: 1103-1104
Editorial: "Ensuring drug safety: lessons from the thiazolidinediones" The Lancet 2007; 370: 1101

EASD: Retrospective Review Suggests Cardioprotective Benefit with Pioglitazone (Actos)

AMSTERDAM, Sept. 19 -- Treatment regimens for type 2 diabetes that include pioglitazone (Actos) were associated with lower risk of stroke and myocardial infarction, claimed investigators for the drug's maker.
The analysis of insurance claims for more than 66,000 patients with type 2 diabetes revealed a relatively low incidence of both stroke (3.36% in the pioglitazone patients versus 4.22% in patients on other therapies) and MI (0.86% in the pioglitazone group versus 1.42% in controls), according to findings reported at the European Association for the Study of Diabetes meeting here.
Those differences, however, translated into adjusted relative risks among patients on pioglitazone of 0.80 (95% confidence interval, 0.7158 to 0.8932, P<0.0001) for stroke, and 0.62 (95% CI, 0.5031 to 0.7661, P<0.0001) for MI, reported Robert Spanheimer, M.D., senior director of diabetes and metabolism at Takeda, and colleagues, from the company.
Moreover, the retrospective findings appear to confirm a meta-analysis published earlier this month in the Journal of the American Medical Association. (See: Ups and Downs of Thiazolinediones for Diabetes Assessed by Dueling Meta-Analyses) In that study, pioglitazone appeared to reduce the risk of stroke, MI, or death by 18% (P=0.02).
A meta-analysis of rosiglitazone (Avandia) published in the same issue of JAMA revealed a 42% increased risk of non-fatal MI (P=0.02) among patients with type 2 diabetes who used rosiglitazone.
But both drugs were associated with significant increases in the risk of heart failure. For rosiglitazone, the increased risk was more than 200% (P<0.005) and for pioglitazone it was 41% (P=0.002).
Commenting last week on the JAMA papers, Dr. Spanheimer said the benefit reported for pioglitazone, "confirms the results of the prospective PROactive study and expands the patient population."
But he also cautioned that, because the 10% reduction in MI and stroke in the PROactive study was not statistically significant, the trial did not meet its primary endpoint. "Therefore, we cannot talk about efficacy in reducing macrovascular events."
In the current study, Dr. Spanheimer and colleagues searched the i3 Innovus database, which includes data on more than 27 million patients in managed care plans to identify patients treated for type 2 diabetes from 2003 through 2006.
They compared outcomes for 11,433 patients treated with pioglitazone with or without other therapies to 55,273 patients who received any antidiabetes therapy other than pioglitazone or rosiglitazone.
The outcome was the incidence of stroke or MI as defined by ICD-9 codes.
The index date was defined as the start date for the initial antidiabetes medication. Patients were included if they were 45 or older at the index date, had continuous enrollment data available for at least six months before and one month after the index date, and did not have a record of stroke or MI in the six months before the index date.
"We conclude that, in a clinical practice setting in patients with type 2 diabetes, therapies that include pioglitazone are associated with significant reductions in the risk for stroke or MI compared to non-thiazolidinedione therapies," they wrote.
The study was funded by Takeda. The authors are employees of the company. Primary source: European Association for the Study of Diabetes Annual Meeting
Source reference: Xu Y et al. "Risk of stroke and myocardial infarction is reduced in patients with type 2 diabetes treated with pioglitazone: results of a retrospective, claims-based study." Abstract 1257, presented Sept. 19.

Glaxo Diabetes Drug Is Dealt Fresh Blows

By JEANNE WHALEN

Two new studies dealt fresh blows to diabetes drug Avandia and boosted rival treatment Actos, as Avandia's maker, GlaxoSmithKline PLC, continues to fight safety concerns about one of its major drugs.
The articles, published online by the Journal of the American Medical Association, follow months of debate about the cardiovascular risks of Avandia, which was Glaxo's second-biggest drug last year with global sales of £1.65 billion ($3.35 billion).
The Food and Drug Administration is considering whether Avandia's use should be restricted. In July, an FDA advisory committee found that Avandia was tied to a risk of heart attacks, but stopped short of recommending that the drug be pulled from the market.
Some doctors have been switching their patients to Takeda Pharmaceutical Co.'s drug Actos from Avandia because they have generally perceived Actos as being safer for the heart. The new papers in JAMA could accelerate that trend. One concluded that Actos appears to reduce patients' risk of heart attack, stroke and death. The other paper confirmed some earlier studies suggesting that Avandia raises patients' risk of heart attack. The studies didn't compare the drugs against each other.
Actos is the only other marketed drug that works in the same way as Avandia. Before concerns about Avandia surfaced in May, the two drugs were selling neck and neck in the U.S. By mid-July, Avandia had dropped to 33% of the U.S. market while Actos had soared to 67% of the market. Yesterday, a Glaxo spokeswoman said that Avandia prescriptions have started to rebound over the past two weeks.
Glaxo, in a statement, said the papers "do not confirm a difference in the safety profile" of Avandia and Actos. The studies "do not yield data robust enough to guide doctors in selecting appropriate diabetes treatments for patients," Glaxo said. Glaxo, of the United Kingdom, said the totality of evidence available on Avandia shows that it is as safe for the heart as Actos and other oral diabetes drugs.
Bob Spanheimer, senior medical director for diabetes at Takeda, said the Japanese company would promote the new studies in JAMA about Actos to doctors and patients. Together with other data, the JAMA results "really should give physicians the confidence to prescribe Actos," he said.
In one of the JAMA papers, cardiologists from the Cleveland Clinic analyzed 19 previous clinical trials of Actos and found patients taking Actos had 18% less of a chance of dying from any cause or having a nonfatal heart attack or stroke than those in the control group. Heart attack, stroke or death occurred in 375, or 4.4%, of 8,554 patients taking Actos and in 450, or 5.7%, of 7,836 patients taking other drugs or placebo. The study was funded by Takeda; three of the four authors reported receiving research support or consulting fees from Takeda and other drug companies.
In a separate paper, physicians from Wake Forest University School of Medicine analyzed four clinical trials of Avandia lasting at least one year each. They found that patients taking Avandia had a 42% greater chance of having a heart attack than those in the control group. Heart attack occurred in 94, or 1.46%, of 6,421 patients taking Avandia and in 83, or 1.05%, of 7,870 patients taking other medications or placebo. Similar findings were published in May, by Cleveland Clinic cardiologist Steven Nissen.
Both studies in JAMA were meta-analyses, which means researchers pooled previous clinical studies for analysis. The authors acknowledged that the meta-analysis technique is flawed because it attempts to draw conclusions from studies that were designed and conducted differently.

Study Suggests How Two Diabetes Drugs May Exacerbate Heart Failure

NEW YORK, Sept. 6 -- Experiments in mice suggest that the type 2 diabetes drugs rosiglitazone (Avandia) and pioglitazone (Actos) increase uptake of both glucose and triglycerides in cardiac tissue, causing or exacerbating heart failure.
Transgenic mice bred to over-express the nuclear receptor targeted by the drugs (peroxisome proliferator-activated receptor-gamma, or PPARg), developed dilated cardiomyopathy associated with increased lipid and glycogen stores, reported Ira J. Goldberg, M.D., of the Columbia College of Physicians and Surgeons here, and colleagues.
What's more, signs of heart failure worsened when mice bred for low-level overexpression were exposed to rosiglitazone, the authors wrote in a study published online today by the Journal of Clinical Investigation.
"While PPARγ agonists appear to have multiple beneficial effects, their direct actions on the myocardium have the potential to lead to deterioration in heart function," they wrote.
Rosiglitazone and pioglitazone, two of the most widely prescribed drugs for type 2 diabetes, are PPARg agonists. Both carry black-box warnings about the potential for the drugs to cause or exacerbate congestive heart failure. The drugs are not recommended in patients with symptomatic heart failure, and are contraindicated in patients with established New York Heart Association Class III or IV heart failure.
"In some rodent models of lipotoxic dilated cardiomyopathy, PPARγ agonist treatment improves heart function," the investigators wrote. "It has been postulated that PPARγ agonists have salutary effects due to direct actions on the heart; this is surprising, since PPARγ causes lipid accumulation in other tissue."
Since one of the actions of PPARγ agonists is to channel plasma triglycerides and fatty acids to adipose tissue, it's possible that doing so might reduce lipid uptake by cardiac myocytes, thereby reducing lipotoxicity, the authors speculated.
To evaluate the cardiac effects of PPARg agonists, the authors bred two strains of mice that overexpress PPARg at either low or high levels. They found that both lines of mice had increased cardiac expression of genes that encode for fatty acid oxidation, as well as increased uptake of triglycerides compared with wild-type animals.
The hearts of the transgenic mice also had dilated left ventricles, impaired systolic function, and increased heart-to-body ratios at four months in the high-PPARg expression animals, and at eight months in the low-expression mice, with the high expression mice having more severe cardiac dysfunction, greater left ventricular systolic dimension (P<0.001) and a greater reduction in fractional shortening (P<0.001).
The expression of genes for brain-type natriuretic peptide and atrial natriuretic factor, both markers for heart failure, was increased in the high-expression mice by four months, and in the low expression mice by eight months.
When the authors exposed eight-month-old low-expression mice to rosiglitazone, the treatment caused further deterioration of cardiac function, including increased lipid accumulation, larger hearts, and decreased fractional shortening.
In addition, when they compared PPARg expression levels in the hearts of wild-type mice, mice with streptozocin-induced diabetes, and human hearts, they found that the diabetic mice had two-fold greater expression of the receptor than the wild-type mice, and the expression in human hearts was about eight to 14 times higher than in wild-type mice, suggesting that PPARg has greater physiologic effect in human hearts, the authors wrote.
"It is possible that cardiotoxic effects of PPARγ agonists in humans occur due to glucolipotoxocity," they wrote in their conclusion. "Fortunately, this is seen in only a minority of patients whose diabetes and perhaps genetic variation make them unusually sensitive to what is otherwise a useful form of therapy."
The study was funded by grants from the Specialized Centers of Clinically Oriented Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest. Additional source: Journal of Clinical InvestigationSource reference: Goldberg IJ et al. "Cardiomyocyte expression of PPARγ leads to cardiac dysfunction in mice." J. Clin. Invest. doi:10.1172/JCI30335.

Boxed Heart Failure Warning Added to Two Diabetes Drugs

ROCKVILLE, Md., Aug. 14 -- The makers of rosglitazone (Avandia) and pioglitazone (Actos), have agreed to add a black box warning to the type 2 diabetes drugs' labels about an increased risk of heart failure, the FDA said today.
The congestive heart failure warning has been in the works for several months and it does not reflect recommendations of an FDA advisory committee that met July 30 to review the cardiovascular safety of rosiglitazone.
That advisory committee agreed that rosiglitazone was associated with an increased risk of ischemic heart disease and recommended that the rosiglitazone label be changed to reflect that.
The boxed warning will also be added to the labels of several combination products that contain the two drugs-Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin) and Duetact (pioglitazone and glimepride). The upgraded warning emphasizes that the drugs may cause or worsen heart failure in certain patients.
The link between the drugs and increased risk of heart failure has been well known for some time, but the "drugs are still being prescribed to patients without careful monitoring for signs of heart failure," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research. That lack of caution prompted the boxed warning, he said.
The FDA's review of adverse event reports found cases of significant weight gain and edema-warning signs of heart failure. In some reports, FDA noted, continuation of therapy has been associated with poor outcomes, including death.
The strengthened warning advises clinicians to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath, and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their health care providers to discuss alternative treatments.
The warning also states that these drugs should not be used by patients with serious or severe heart failure who have marked limits on their activity and who are comfortable only at rest or who are confined to bed or a chair.
Rosglitazone is made by GlaxoSmithKline and pioglitazone is a Takeda product.

Diabetes drugs to include new warnings

Tue Aug 14, 8:14 PM ET
The diabetes drugs Avandia and Actos will be labeled with severe warnings about a risk of heart failure to some patients, health officials said Tuesday.
The makers of the drugs, GlaxoSmithKline Plc and Takeda Pharmaceutical Company Ltd., have agreed to add the "black-box" warnings, the Food and Drug Administration said. The warnings, the most severe that prescription drugs can bear, stress the medicines may cause or worsen heart failure and that patients should be closely monitored.
The warnings also apply to combination drugs that include the active ingredients in Avandia, made by Glaxo, or Takeda's Actos. The drugs help patients with Type 2 diabetes control their blood sugar levels.
The warnings, which the FDA said in June it would seek, are separate from concerns that Avandia also raises the risk of heart attack. FDA advisers said last month the risk appeared real but that the evidence wasn't conclusive enough to merit pulling Avandia from the market. They did recommend Avandia's label be updated to include information on that risk. The FDA said it was continuing its review of the issue.
Separately, an FDA review of reports of side effects in patients taking either Avandia or Actos found cases of significant weight gain and build up of fluids, both of which are warning signs of heart failure, the agency said.
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On the Net:
FDA Avandia information: http://www.fda.gov/cder/drug/infopage/rosiglitazone/default.htm
FDA Actos information: http://www.fda.gov/cder/drug/infopage/pioglitazone/default.htm