Safety concerns raised over new diabetes drug
Cardiovascular safety needs to be addressed in further trials |
Safety concerns over a new drug to treat type 2 diabetes have been raised in a paper published online in JAMA on
20 October.
On 18 October, the US Food and Drug Administration issued an “approvable
letter” for dual peroxisome proliferator-activated receptor agonist,
muraglitazar, which is indicated as monotherapy for type 2 diabetes and
as combination therapy in patients with blood glucose not adequately
controlled with metformin. Steven Nissen, department of cardiovascular
medicine, Cleveland Clinic Foundation, Cleveland, Ohio, and colleagues
analysed data submitted to the FDA and found “concerning” results.
Their analysis included data from five trials, ranging from 24 to 104
weeks, involving 3,725 patients who received differing doses of muraglitazar,
pioglitazone or placebo as monotherapy, or in combination with metformin
or glyburide. The researchers found that 35 out of 2,374 patients in
the muraglitazar group died or had a myocardial infarction or stroke
compared with nine out of 1,351 patients in the combined placebo and
pioglitazone treatment groups (relative risk 2.23, 95 per cent confidence
interval 1.07–4.66; P=0.03).
If the outcome measure additionally included transient ischaemic attacks
and congestive heart failure, the incidence was 50 of 2,374 in muraglitazar
patients compared with 11 of 1,351 controls (2.62, 1.36–5.05; P=0.004).
The researchers note limitations of their analysis, including no access
to the original trial databases and the consequent use of simple chi-squared
analysis rather than time-to-event methods. However, they conclude: “Muraglitazar
appears to increase the risk for morbidity and mortality in diabetic
patients during relatively short-term treatment.” They recommend
that it should not be used or approved until an appropriate dedicated
trial to assess cardiovascular outcomes is performed.
In a press release, Bristol-Myers Squibb (developers of the drug in collaboration
with Merck), said: “The FDA requested additional information from
ongoing trials to more fully address the cardiovascular safety profile
of muraglitazar. We and our partner, Merck, have determined that to receive
regulatory approval and to achieve commercial success, additional studies
may be required because the ongoing trials were not designed to answer
questions raised by the FDA.” BMS predicts that these studies may
take five years and adds that it will consider a range of options including
terminating further development of muraglitazar. |
The
Pharmaceutical Journal
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