Irrational medicines use - a comparison of metformin fixed dose combination drugs in India, Australia and England

P McGettigan1, A Pollock1, P Roderick1, R Mahajan2, A Khadam2, N Mistry2. 1Queen Mary University of London, London, UK, 2Foundation for Research in Community Health, Mumbai, India

Background: In India for over thirty years, parliamentary reports have highlighted the proliferation of irrational drugs, especially fixed dose combination (FDC) products, and raised concerns about the rigour of the medicines approvals process. In a small field study of medicines access, we found large numbers of metformin FDCs for diabetes treatment. However, neither national nor international diabetes management guidelines recommend the use of FDCs and they are not included on the World Health Organisation’s Model List of Essential Medicines or on the Essential Medicines List of India. We therefore investigated regulatory approvals for and use of metformin FDCs in India compared with two countries that apply stringent regulatory processes, Australia and England

Methods: We examined regulatory approvals and medicines sales data from India and approvals and drug dispensing data from England and Australia.

Results: Of 23 different metformin FDC formulations marketed in India, seven had no record of approval by the national regulator, the Central Drugs Standard Control Organization (CDSCO). While sixteen FDCs had CDSCO approval, branded products of ten were marketed prior to the approval date. By 2012, the 23 FDC formulations had given rise to over 500 branded products including 137 different metformin/glimeperide products. In 2012 in Australia, there were four approved metformin FDCs, in England, five, and similar numbers of branded products.

Metformin FDCs accounted for 49% of oral diabetic drug sales in India in 2007/08 and increased to 56% by 2011/12. They comprised 3.7% of oral diabetic drugs dispensed in Australia (2010) and 1.1% in England (2011). Of eleven metformin FDC formulations marketed in India by pharmaceutical multinational companies (MNCs), just four were also marketed in Australia and/or England.

Conclusion: Stringent drug regulatory processes help ensure that marketed medicines are effective and safe. In India, most metformin FDCs were marketed without prior regulatory approval suggesting deficiencies in the approvals process and failure to comprehensively assess safety and efficacy. Despite this and the absence of recommendations for their use, metformin FDCs increasingly dominate oral treatments for diabetes in India. In contrast, in Australia and England, they are not commonly used and MNCs have marketed many fewer FDCs than in India. CDSCO needs to strengthen its drug approval processes and remove non-approved metformin FDCs from the market.