New Delhi: Despite new evidence that suggested diabetes drug pioglitazone, sold as Actos by Japanese drug maker Takeda Pharmaceutical Co. and copied by 50 different drug makers in India, reduced the risk of heart attacks, some doctors in India said they are not ready to lower their guard against this class of drugs.

Indeed, related research, to be published on Thursday in the Journal of the American Medical Association (Jama), says that a rival diabetes drug, rosiglitazone, sold as Avandia by GlaxoSmithKline Plc., increased heart attacks by 42% and doubled rates of heart failure. Jama is also reporting that Actos reduced heart attacks, strokes and deaths by 18%, but it also increased heart failure. Takeda funded the Actos study.

Both Jama articles analysed data from previous studies, a method known as meta analysis. The Avandia study, by doctors at Wake Forest University in Winston-Salem, North Carolina, looked at four trials that enrolled 14,291 people for at least 12 months. They found no increased rate of death from cardiovascular causes. The Actos study analysed data from 16,390 people treated in 19 trials that ranged from 16 weeks to 3.5 years.

Both Actos and Avandia are in a class called thiazolidinediones, or glitazones, which help the body use insulin more effectively.

Meanwhile, many Indian doctors have already been switching patients on to other, older drugs and most have urged caution stemming from recent concerns over Avandia.

“The studies will keep coming and they can create confusion. One should have reservations about these drugs and use them judiciously," said Anil Gomber, a senior consulting diabeto-cardiologist with Max and Tirath Ram hospitals here. Gomber says he switched around 40 of his patients from glitazones to other medications.

India is home to 43 million diabetics, of which 10 million are believed to be on this category of drugs, made by several generic drug companies here. The anti-diabetic market alone is pegged at Rs1,362 crore.

Rosiglitazone is sold by 10 drug makers under different brand names in India and pioglitazone by at least 50 companies, including Cipla Ltd, Glenmark Pharmaceuticals Ltd, Sun Pharmaceuticals Ltd and Torrent Pharmaceuticals Ltd.

“As a department, we have always been cautious of glitazones and use them very sparingly. In fact, we prescribe them only as a third line of medication after metformin and sulfonylurea," said Nikhil Tandon, professor of endocrinology at the All India Institute of Medical Sciences.

Doctors say they were being cautious about the entire category thiazolidinediones. These were once hailed as a panacea for diabetes but have fallen out of favour amid recent adverse reports.

Another physician, who didn’t wish to be named, said there was so much literature inundating doctors including some contradictory information that it was hard to sift through all of it. “The liver story is over, but the heart story is here now," he said, referring to how this class of drugs was initially investigated for impairing liver functions though evidence of that has never fully materialized.

Avandia had revenues of $3.38 billion (Rs13,674 crore) in 2006. Its prescriptions, however, have fallen by by more than half to 146,000 a week since a New England Journal study was published on 21 May, according to IMS Health Inc. and Citigroup Inc. That study, for the first time, linked Avandia to increased heart risks. Avandia now accounts for 5.6% of new US prescriptions for diabetes pills, compared to nearly 14% for Actos as patients switched drugs in US. Both the drug were given “black box" warning labels by the US Food and Drug Administration last month.

Officials at London-based Glaxo, Europe’s largest drug maker, said the Jama findings conflict with accumulated data on Avandia from 116 clinical trials in more than 52,000 patients, which they said don’t show the drug reduces blood flow to the heart compared with other medicines, including Actos. Reduced blood flow to the heart can cause heart attacks.

“I don’t think it adds any new information on the safety of Avandia at all," Glaxo vice-president Alastair Benbow said. “We believe Avandia remains an important option for doctors and their patients."

Steven Nissen, a co-author of the Jama article about Actos and the 21 May New England Journal study of Avandia, said regulators should act on the two Jama articles.

“It’s quite a contrast to look at the two analyses side by side," Nissen said. “It puts pressure on regulatory agencies around the world to take some sort of action on rosiglitazone."

Bloomberg’s London and Minneapolis reporters contributed to this story.