"India is the diabetes capital of the world!"
That was a headline two years ago in the Times of India. And that's not a case of media hype. India has a huge diabetes problem: nearly 70 million people are grappling with the disease.
India also has a prolific pharmaceutical industry pumping out hundreds of innovative drugs to treat diabetes and other ailments. But researchers say it's unclear how well some of these medicines work, or even if they're safe, because the drugs haven't gone through adequate clinical trials.
"We're really puzzled as to why many of these medicines are available," says Allyson Pollock, the director of the Institute of Health and Society at Newcastle University in England, "because some of these weren't even approved by the medicines regulator in India."
Pollock and her colleagues have just come out with an analysis of regulatory approval procedures for diabetes drugs in the Indian state of Maharashtra. The findings reinforce her skepticism.
One example involves the drug metformin, a workhorse of diabetes treatment. According to the Mayo Clinic metformin is usually the first medicine prescribed to people with type 2 diabetes, helping control high blood sugar. In the U.S. most metformin comes in pills in which metformin is the only active ingredient.
But not in India. "To our absolute amazement we found that metformin was not the most frequently available medicine," she says. "Instead we found huge numbers of what's called fixed dose combinations."
Fixed dose combinations, known in the pharmaceutical industry as FDCs, are pills that deliver two or more drugs. Most metformin in India is sold in FDCs containing some other medication as well. Indeed, regulators in India have approved 52 metformin fixed dose combinations. Indian pharmaceutical companies are marketing those combos under more than 500 different brand names.
The argument in favor of FDCs is that they improve patient adherence to drug regimens. Diabetics who have to take several drugs a day for instance may have to only have to take a single pill.
But there's growing concern that due to lax government oversight, India's incredibly powerful pharmaceutical industry is flooding the market with unnecessary and untested drug cocktails.
In 2016 the Ministry of Health banned 344 FDCs for a wide range of medical conditions including diabetes, saying that the combinations had "no therapeutic justification."
Pharmaceutical companies went to court to get the ban lifted. The challenge has gone all the way to the Indian Supreme Court. And while the legal battle continues to play out, the once-banned FDCs have been allowed back on the market.
Dinesh Thakur, who's worked in the Indian pharmaceutical industry and now runs a consulting firm out of Florida called MedAssure, says part of what's driving the proliferation of FDCs in India is profit.
"There is usually a three-to-six fold price increase for these unregulated fixed dose combinations compared to pure metformin sold as a generic," he says. Generic metformin sells in India for just over one U.S. cent per 500 milligram pill. A combo of metformin and another generic diabetes drug, repaglinide, sells in India under the brand name Reglide-Plus for roughly 18 cents a pill. The two generics if bought separately cost about 8 cents. So the profit per pill isn't huge but adds up when you consider the tens of millions of people in India with diabetes.
And then there's the matter of regulation. Health activists in India say that it's being left to the companies to decide whether these drug combos are safe or even effective. Thakur says that there should be more rigorous examination of FDCs, particularly for drugs for chronic conditions that people could take for the rest of their life.
Thakur adds that this practice of combining drugs has been going on for years — and that customers essentially are getting ripped off. "There is basically zero evidence that 99 percent of these things actually do anything clinically important," he says.
And that's the point that Pollock at Newcastle University makes as well: There's no independent research on most of these FDCs to determine how well they work or if they might cause unwanted side effects. Most wouldn't be allowed to be sold in Europe, North America or even many developing countries.
Pollock's paper found the five top-selling metformin FDCs accounted for 80 percent of all metformin sales in India in 2012. For some of them, no clinical trials were conducted before the products hit the market. Of the studies that were done, none met the World Health Organization's guidelines.
"India's got a population of a billion," she says. "We are finding there are almost no clinical trials being conducted in India. And the clinical trials they are doing are so weak they do not match meet the standards of the WHO in terms of the number (of participants), the duration of the trial or studies of harmful effects."
These controversial diabetes drugs are primarily being sold inside India. But Pollock points out that any potential problems with these medicines are unlikely to affect only Indians. India has come to be known as the "Pharmacy for the Developing World." Its cheap drugs find their way to markets all over the planet. Visitors also may stock up on medications before heading home given that the drugs there are relatively inexpensive.
"This is an international health issue," Pollock says. "Here in the U.K. we have many people from the Indian subcontinent who go home and bring their medicines back. And of course you've got internet sales. So really India has to get its act together."
But that's unlikely to happen if the responsibility for conducting clinical trials and vetting new medicines is left to the pharmaceutical companies as it now is.
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