There is growing evidence that the ban the Union Health Ministry imposed on June 18 on pioglitazone — a widely used anti-diabetes oral drug — was taken with undue haste and in great secrecy.
There was no large-scale scientific study undertaken to know the risk of bladder cancer caused by the drug before imposing the ban. The drug was approved for use in India in early 2000s and many thousands are on this drug.
According to media reports, theexpeditious decision to ban the drug was taken by keeping the Drug Technical Advisory Board in the dark.
Ironically, the first ever meeting to discuss the safety profile of the drug was undertaken on July 11, after the ban. The expert committee meeting was convened when the government came under severe flak from diabetologists across the country. The expert committee wanted the ban to be revoked.
According to a Health Ministry official, the whole issue has now been referred to the Drug Technical Advisory Board, which will meet on July 19. There are indications that the government may revoke the ban within a few weeks of imposing it.
Ironically, the government acted based on a letter sent by a few doctors, including the Chennai-based diabetologist Dr. V. Mohan, chairman of Dr. Mohan’s Diabetes Specialities Centre. Dr. Mohan’s letter was based on his observation of eight bladder cancer cases in those on pioglitazone drug.
“I had written a letter to the Drug Control General of India (DCGI) in January [asking him] to consider a ban. It was my opinion,” said Dr. Mohan to The Hindu. “We saw eight cases of bladder cancer [in patients on pioglitazone] and published it in the Journal of Association of Physicians of India (JAPI). There are 1,200 lawsuits in the U.S. field by patients who are on pioglitazone. Doctors can get sued, so I felt like informing the DCGI. I sent the letter in good faith.”
Asked why he did not ask that scientific studies be undertaken instead of calling for a ban — especially since Indian data on the drug’s safety is not known — Dr. Mohan said: “I could have done it…maybe I erred in my judgement…I did it in good faith. I thought the DCGI would do it…undertake a study.” In a January 2012 paper published in JAPI he had himself noted: “we require more robust data on the risk of bladder cancer with pioglitazone and Indian studies are clearly needed.”
Even the information about the eight bladder cases published in the journal was only a letter to the editor and not a research article. Unlike research articles, letters to editor are not peer reviewed and hence have very little scientific credibility.
MSD, the Indian subsidiary of Merck, would stand to gain the most from any ban on pioglitazone. MSD’s gliptin (Januvia) costs Rs.42 for a tablet and is one of the main replacements for pioglitazone, which costs Rs.5 a tablet.
MSD has been funding a certificate course run by Dr. Mohan’s Diabetes Education Academy for the last two years. Dr. Mohan refused to divulge the amount or percentage of funding he gets from the company.
“PHFI is the implementing partner for the course supported by MSD through an educational grant,” a PHFI spokesperson noted in an email to The Hindu. “[The course] is to train and sensitise primary health care physicians for effectively preventing, diagnosing and treating diabetes in a large number of individuals, families and communities.”
France is the only other country to have banned the drug. The USFDA requires only a box warning to be carried and Germany recommends that the drug not be given to new patients. But the dosage used abroad is as high as 40-45 mg a day compared with 15 mg a day in India. “When we use 30 mg a day we would reach the cumulative dose of 28,000 mg in less than three years,” Dr. Mohan noted.
Dr. Balaji, Director of a diabetes centre in Chennai, said: “Several thousand patients are on pioglitazone and if it causes bladder cancer in a few years we should have seen hundreds of cases. That is not the case.”
It is a well known that Indians have a very different genetic makeup and hence are more vulnerable to becoming diabetic compared with Caucasians. Unlike Caucasians, diabetes strikes even slim Indians. “For the same body weight, Indians are 1.5 times more insulin resistant than Caucasians,” Dr. Balaji said. “And the ratio of visceral fat to subcutaneous fat is higher in the case of Indians. That is why doctors use waist circumference to measure abdominal obesity, a surrogate marker to know the predisposition to diabetes.”
Considering the differences in the genetic makeup of Indians and their susceptibility to diabetes, it becomes all the more important to carry out many studies here in India to understand the safety profile of the drug. Unfortunately, all available literature on bladder cancer risk is based on data from other countries.
Probably the only study to evaluate bladder cancer risk in Indians who are on pioglitazone was published in July in the Indian Journal of Endocrinology and Metabolism. The study by Dr. Balaji, which looked at the safety profile of 958 patients who are on three different pioglitazone dosages (7.5 mg, 15 mg and 30 mg a day), did not find any “increased risk of bladder-related abnormalities across all treated age groups even after two years of treatment.”
“The risk: benefit is tilted heavily in favour of pioglitazone,” notes an editorial published in May in the Indian Journal of Endocrinology and Metabolism. “The number of patients required to be exposed to pioglitazone to cause one bladder cancer is too high when compared to the number of deaths prevented by its prescription.”