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Diabetes mellitus is a common chronic disease that is already pandemic, and hyperglycaemia plays a key role in the development of diabetes complications. In the last 15–20 years, we have witnessed a dramatic improvement of the ‘armamentarium’ developed by the pharmaceutical industry for treating diabetes. The objective of this review is to examine cases of relevant differences for these compounds in terms of approval, rejections, withdrawals and different labelling, between the US FDA and the European Medicines Agency (EMA) that have occurred since 1994, which was the date of the US approval of metformin. Cited examples include troglitazone, vildagliptin, liraglutide and the class of thiazolidinediones (TZDs) or ‘glitazones’. We looked at the labelling of TZDs and the different evaluative approaches for rosiglitazone performed by the FDA and EMA last year. The latest assessment on pioglitazone from both agencies is also included in this review.
It is difficult to understand the reasoning behind different decisions in these two regions. They might relate to the approval itself, likely due to a different benefit/risk assessment approach, or to the use of different guidances or guidelines. Differences in timing are also notable between the regions, even when licensing applications are submitted at the same time in both the US and Europe. It is easy to understand the need for a prolonged assessment time for the approval of a drug when more data are required by a regulatory agency (e.g. specific race-related findings from phase I studies or safety data in a specific target population, such as the elderly); however, many delays are not related to such requests. In addition, we looked at the timing of withdrawals of some new diabetes medicines, which also sometimes vary between regions.
These different assessments have a negative impact on patients with diabetes, in terms of finding their own medications if they travel or live abroad, understanding their use and ultimately feeling reassured by a worldwide consistent safety profile. Regulatory agencies should be aligned in their requirements to clearly guide manufacturers in the clinical development of future innovative medicines in order to improve the treatment of diseases such as diabetes that present on a very large and costly scale and are growing in prevalence. We would welcome in the new millennium, the harmonization of criteria for the assessment of experimental antidiabetic therapies and the timing of approvals and withdrawals, as well as a uniformed labelling of diabetes drugs from the FDA, EMA and from any other regulatory agency.
KeywordsMetformin Bladder Cancer Rosiglitazone Pioglitazone Liraglutide
No funding was provided for the writing of this review. Dr Domenico Merante is an employee of Daiichi Sankyo. Professor Antonio Ceriello had no conflicts of interest to declare that are directly relevant to the content of this review.
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