New Delhi, July 8: The proliferation and sales of anti-diabetes combination pills that contain two drugs to control blood sugar has stirred concerns in medical circles that a large proportion of diabetes patients in India are not receiving ideal treatment.
A study by Indian and British researchers has shown that such two-drug combo pills accounted for more than half of the sales of all oral anti-diabetes medications in India last year, although doctors say there is no need for combo pills in diabetes management.
The study has also revealed what the researchers say is a conspicuous absence of evidence for safety and efficacy of at least four such two-drug combos that make up 297 brands of oral anti-diabetes medications sold in India.
“Doctors in most parts of the world would throw up their hands in horror at the proliferation and widespread use of such combination pills in diabetes,” said Allyson Pollock, professor of public health research at Queen Mary, University of London, and a study team member.
“Taking combo pills is not a good idea — when patients require two drugs, they need to swallow two pills, not one,” said Nihal Thomas, professor of endocrinology at the Christian Medical College, Vellore, who was not associated with the study.
Metformin should be taken with or after a meal, he said, while drugs from another class of compounds should be taken before food. A patient who takes a single pill that contains both drugs is unlikely to be receiving appropriate therapy.
Pollock and her colleagues conducted a systematic review of all documented clinical trials worldwide involving four top-selling two-drug combo pills containing metformin and one of three other drugs — glimepiride, glipizide, glibenclamide and gliclazide.
While the Central Drugs Standards Control Organisation (CDSCO), the agency that gives marketing approval to drugs, has cleared 102 brands of metformin with gliclazide since 2003, the researchers could not find even one clinical trial of this combination on patients with diabetes.
Most trials on the other three combo formulations with metformin were short-duration studies and prevent a “thorough evaluation” of the combination pills for safety and efficacy, Pollock said, presenting the findings at a conference here last Friday.
The study reinforces concerns expressed by a parliamentary standing committee on health last year that India’s drug regulators had done nothing about the sale of combination pills that had not been approved — and are thus illegal — or those not proven to be safe and effective.
Both pharmacological science and Indian drug laws demand that a single pill combining two or more drugs — which have individually already been approved for use in humans — should be viewed as a novel drug requiring evaluation for safety and efficacy.
“The rising sales of combo pills is indirect evidence of what doctors are prescribing — it’s a signal that many diabetes patients aren’t being managed well,” said Rushikesh Mahajan, a researcher with the Foundation for Research in Community Health, Mumbai, a NGO that collaborated in the study.
Combination pills for diabetes are not commonly found in the US, UK or Australia.
“I’m personally against such combination drugs — giving (two) drugs separately is pharmacologically rational. It also helps us identify individual drugs if patients experience any adverse effects,” said Anoop Misra of Fortis Hospitals, New Delhi.
Misra and others also point out that formulations of single drugs also allow patients to receive exact doses of the two drugs they may need. “In diabetes, often we cannot predict the ideal or effective doses for a patient,” said Jothidev Kesavdas, an endocrinologist and diabetes researcher in Thiruvananthapuram. Combination pills have fixed doses of two or more medications. “When we prescribe two drugs separately, we can more easily tailor the dosage of both to the individual patients’ needs,” Kesavdas said.
But, he said, patients often prefer combo pills because they have to swallow fewer tablets.
Last week, the CDSCO , the standards control organisation, set an August 31 deadline for firms to provide safety and efficacy data on combo drugs in the market. The research by Pollock and her colleagues suggests that there is scant safety and efficacy data for even the approved combo pills.