Philadelphia, PA - The FDA has updated the prescribing information for the diabetes drug rosiglitazone (Avandia, GlaxoSmithKline) to include findings from the ADOPT trial.
The trial, a four- to six-year head-to-head study of rosiglitazone vs metformin and glyburide monotherapy in recently diagnosed type 2 diabetes patients, showed better glycemic control with rosiglitazone than with the other two agents. At five years, 15% of patients on rosiglitazone had inadequate glucose control, compared with 21% on metformin and 34% of those taking glyburide.
Safety information showed a similar incidence of congestive heart failure in the rosiglitazone and metformin groups (0.8% each), but a lower incidence in the glyburide group (0.2%). Significantly more women treated with rosiglitazone experienced fractures (mostly in the upper arm, hand, or foot) than those on metformin or glyburide. The incidence of fractures in men was similar among the three treatment groups.
Other cardiovascular safety data from ADOPT were added to the label in November 2007 and show that the results for three end points (major cardiovascular events, MI, and total mortality) were not statistically significantly different between rosiglitazone and comparators, GlaxoSmithKline states in a press release.
Nissen critical
But rosiglitazone critic Dr Steve Nissen (Cleveland Clinic) says the new addition to the labeling is not relevant given the concerns over increased cardiovascular risk with the drug. He commented to heartwire: "In ADOPT, blood sugar showed better control, but the relative risk of MI was 33% higher with rosiglitazone." He noted that although this was not statistically significant by itself, the results were consistent with the four meta-analyses that showed an increased MI risk with rosiglitazone and led to a black-box warning being added to the rosiglitazone label because of increased risk for ischemic myocardial events. "Having more sustained control of blood sugar isn't particularly useful if the drug also increases the risk of MI," Nissen added.
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July 14, 2008 03:18 (EDT)
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'Critical'
No surprise there. I'm a little confused by his commentary (33% RR) however and maybe someone else can plug in the numbers better than I.....
I looked at ADOPT in NEJM again and noted participants 1456, 1454, 1441 on tzd, met, su over 4-5 years.
Of those people there were CV events of 62, 58 and 41 (tzd, met, su). NS
CHF 22 (no death), 19 (1 death), 9 (1 death). higher chf former 2 vs. latter
MI 25 (1.7%), 21 (1.4%), 15 (1.0%). NS. Is he adding the latter 2 groups dividing by 2 and then making this assumption for 33% increased RR???? I think figure 2 in the article is also powerful at the end of 3 years 957 were still on TZD, 950 on Met and 781 on SU still monitoring for CV events (failure to keep glucose control resulted in dc of med and end of study for that pt) End of 4 years 844, 818, 617 and end of 5 years 324, 311, 218 last year pts still being monitored not necesarrily due to failure at this point. NONE of the 3 groups showed any seperation of Major CV events or Death. It would seem that would be the only conclusion for this and the fact that tzd and met are butter for maintenance of glucose than SU over this time frame in this population.
Stroke 16, 19, 17 in the respective groups. |
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July 15, 2008 11:25 (EDT)
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More Nissen Mischievious Nonsense
Just more embarassment to Cleveland Clinic.
Rosi has been vindicated in legitimate randomized controlled cardiovascular study analyses.
Better to be on Rosi than not (in ACCORD)
MUCH MUCH better to be on Rosi than not (in VADT)
Paul D. Rosenblit MD |
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July 15, 2008 04:05 (EDT)
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Paul,
Is that the MNMN study from CC? :o)
ADA was very good this year and nice outcomes studies. |
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July 22, 2008 10:46 (EDT)
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KUDOS PAUL
If Nissen wants to be taken seriously he should delineate just where the numbers come from. I tried to get 33% to and when I failed I just figured the person that calculated 33% was 33% smarter than me. He appears to be yelling from a soapbox, first rosizlitazone then ezetimibe. The former conclusion was NOT statistically significant (hence alot of use for the word "trending") and the latter used end points that have been called into question.
If on the one hand you have decreased glucose which has been proven to improve endpoints (UKPDS) versus no significant information, which looks better.
I would not have suggested rosiglitazone in the patient population in the study. I have seen alot of exacerbation of HF in older patients with demonstrated CAD and/or HF, particularly when used in conjunction with insulin. But I would use it in at risk patients without overt CAD or HF.
Is Nissen lobbying for the top job at the FDA by putting the talking heads of the network news in his pocket? And aren't the latter a bit melodramatic, creating public "panic" when they should be consulting their primary care/cardiologist? |
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