Over 60 million people in India have been diagnosed with type II diabetes mellitus but the data behind the five most popular drugs has been found to be lacking.
A new study has found that the clinical trial evidence for five of the most popular diabetes drug combinations in India has been inadequate.
The study has been published in the British Medical Journal‘s ‘Global Health’ section. It examines the efficacy and safety of five of the most used metformin fixed-dose combinations (FDC) in India, popularly administered for adults with type II diabetes mellitus. Metformin is a first-line treatment for diabetes.
Over 60 million people in India have been diagnosed with type 2 diabetes mellitus.
“Our examination exposes serious deficiencies in the evidence base for metformin FDCs for type 2 diabetes and raises questions about the role of multi-national companies in manufacturing these for sale and use,” the paper said.
The authors evaluated published and unpublished clinical trial data for the five top-selling FDCs and found that none of them provided robust evidence on safety and efficacy.
“The availability of irrational or inadequately tested medicines puts the safety of the public at risk,” the authors also added. “It is important to ensure that those medicines that are available on the market have been approved after examination for safety and efficacy through the implementation of appropriately designed and analysed clinical trials.”
Their study also references the work of the Indian parliament, which has reviewed the issue of irrational drug combinations in India.
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The five top-selling metformin FDCs for type II diabetes mellitus were:
- glibenclamide/metformin, and
According to the paper, five metformin FDCs in India accounted for 80% of all metformin FDC sales between November 2011 and October 2012, examined by value and volume. “India’s drug regulator has given approval for 52 FDC formulations for type II diabetes, which in turn has given rise to more than 500 marketed brands of metformin FDCs,” according to the paper.
Three of the five top-sellers were sold and marketed prior to receiving any approval from India’s drug regulator. All five were eventually approved.
In 2016, as a result of a public interest litigation in India, 344 of these FDCs were banned because they were irrational. Twenty-seven of them were metformin FDCs, including three of the five. The reason: for having “no therapeutic justification”. The Supreme Court upheld this order in December 2017 and asked the Drugs Technical Advisory Board to study the banned drugs and submit a report.
Despite their top-selling status, the researchers found only one study that had evaluated the efficacy and safety of metformin FDCs; the study itself was found to be “underpowered and of poor quality”.
There were 25 clinical trials for these five FDCs. None of the drugs themselves met four selected criteria of the WHO’s guidelines on the trials and approvals of FDCs.
In 2005, the WHO published a technical report called ‘Guidelines for Registration of Fixed-Dose Combination Medicinal Products.’ The authors of this paper picked four criteria from these guidelines, pertaining to size of sample, duration of trial, design of trial and adverse reactions.
Unlike other drug regulators, India’s Central Drug Standards Control Organisation (CDSCO) does not publicise the evidence it uses to approve drugs and FDCs. The authors concede that more convincing data on these five FDCs could be available with CDSCO but that it was not made available to them.
On what data might be available with the CDSCO, the researchers say, “If that evidence does not extend beyond the trials reviewed here, those FDCs should be banned immediately. If that evidence includes the results of trials not reviewed in this paper, which do not meet the four WHO standards used for evaluation, those FDCs should be banned.”