New drugs - sitagliptin

Editor, – The monograph about sitagliptin (Aust Prescr 2008;31:49-55) states that 'while patients with liver disease may be able to take sitagliptin, it is not recommended for patients with renal impairment'. This is presumably because just over 70% of the drug is excreted unchanged in the urine. There are, however, facts - both in the monograph itself and elsewhere - to refute the quoted statement.

First, as noted in the monograph, the drug is presented in three strengths, 25, 50 and 100 mg tablets; this is solely due to the fact that sitagliptin can be safely given to patients with renal impairment (in doses commensurate with the severity of the renal impairment). Second, both the Australian¹and US²product information for sitagliptin state that, 'for patients with moderate renal insufficiency, the recommended dose is 50 mg daily, while 25 mg daily is recommended and safe for patients with severe or end-stage renal disease (including those on renal replacement therapy)'.

Use of the general phrase 'patients with renal impairment' suggests that this is a distinct and perhaps minor group of patients. It is therefore not only misleading, but clearly inaccurate. Patients with type 2 diabetes who were enrolled in the UK Prospective Diabetes Study were followed for a median of 15 years as part of one of its many sub-studies (UKPDS 74).³At the end of this period, about 40% developed albuminuria and 30% developed 'renal impairment' (with some overlap between the two groups).

Andrew J Lowy
Endocrinologist and Clinical Pharmacologist
Principal Investigator, Australian Clinical Research Centre, Sydney
Expert Reviewer, Endocrine and Metabolic Drugs, Australian Medicines Handbook

The safety of using sitagliptin in patients with renal insufficiency was no doubt considered in the evaluation of the drug by the Therapeutic Goods Administration (TGA). Unfortunately, the TGA does not publish these evaluations and sometimes there can be delays in finalising the Australian product information. It is therefore necessary to consider overseas evaluations when preparing a comment about a new drug.

Dr Lowy is correct that the product information in the USA includes doses for use in renal insufficiency, however the European Medicines Agency (EMEA) took a more cautious approach. Its evaluation found that the data were too limited to confirm the safety of sitagliptin in patients with moderate to severe renal insufficiency.⁴

Clearly, the European, USA and Australian regulatory agencies have assessed the data in different ways. Without more transparency in the Australian system we will not know how the TGA interpreted the evidence.

To try and overcome this problem the Editor wrote to the manufacturer seeking more information about sitagliptin, before the new drug comment was published. There was no reply.