Vildagliptin | place in therapy review Scope, aims, and objectives Vildagliptin (Galvus®, LAF 237, Novartis) is an inhibitor of dipeptidyl peptidase 4 (DPP-4) that has been developed for the treatment of type 2 diabetes. The drug was approved for use in the EU in February 2008 and is available in Mexico and Brazil. DPP-4 is a new therapeutic target for the treatment of type 2 diabetes, and its role and the mechanism of action of vildagliptin are discussed in the Disease overview section below. This article reviews the currently available published evidence on the effects of vildagliptin in type 2 diabetes, and considers its potential for clinical and economic benefit. The primary emphasis is given to clinical studies, but results of preclinical and clinical pharmacology investigations are also summarized. Methods English language literature searches were conducted on October 10, 2005 in the following databases, searching from the beginning of the database to date unless otherwise stated. The search strategy was “(vildagliptin OR laf 237) AND diabetes” unless otherwise stated. • PubMed, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi, 1966 to date. Search strategy, “(vildagliptin OR laf 237) AND diabetes,” was expanded by Automatic Term Mapping to “(((“Vildagliptin” [TIAB] NOT Medline[SB]) OR “Vildagliptin”[Substance Name] OR vildagliptin[Text Word]) OR (“1-(((3-hydroxy-1-adamantyl)amino) acetyl)-2-cyanopyrrolidine”[Substance Name] OR laf 237[Text Word])) AND ((“diabetes mellitus”[TIAB] NOT Medline[SB]) OR “diabetes mellitus”[MeSH Terms] OR (“diabetes insipidus”[TIAB] NOT Medline[SB]) OR “diabetes insipidus”[MeSH Terms] OR diabetes[Text Word]) AND English[Lang].” • EMBASE, http://www.datastarweb.com, 1974 to date. Search strategy: “(vildagliptin OR laf 237) AND diabetes”. • Database of Abstracts of Reviews of Effectiveness (DARE), National Health Service (NHS) Economic Evaluations Database (NHSEED), Health Technology Assessment (HTA), www.york. ac.uk/inst/crd/darehp.htm. All three databases were searched together. All fields searched. • NHS HTA, www.ncchta.org. • National Guideline Clearing House, www.guideline.gov. • National Institute for Health and Clinical Excellence (NICE), www.nice.org.uk. • Cochrane Database of Systematic Reviews (CDSR), www. cochrane.org/index0.htm. Entire site searched. • Clinical Evidence (BMJ), www.clinicalevidence.com. • www.clinicaltrials.gov. • www.clinicalstudyresults.org. After removal of duplicates, a total of 69 records were identified. Records were manually reviewed and 61 were excluded for 14 the following reasons: nonsystematic reviews (n=45); letters, editorials, news items, notes, comments, and corrections (n=13); articles about other drugs or treatments (n=2); articles on other subjects (n=1). Eight papers remained and were included in the evidence base (Table 1). Table 1 | Evidence base included in the review Number of records Full papers Abstracts 69 61 8 0 5 8 0 4 1 1 3 0 15 20 19 6 13 0 35 12 3a 0 0 13 6 9 0 28 Category Initial search records excluded records included Additional papers identified Search update records excluded records included Publications not available on databases and supplied by manufacturer Publications identified from additional sources Level 1 clinical evidence (systematic review, meta analysis) Level 2 clinical evidence (RCT) Level ≥3 clinical evidence trials other than RCT case reports Evidence from animal and in vitro studies Economic evidence Total records included aFour were supplied but one was a duplicate of data presented in a full paper and was excluded. For definitions of levels of evidence, see Editorial Information inside back cover or on the Core Evidence website (http://www.coremedicalpublishing.com). RCT, randomized controlled trial. Meeting abstracts from 2002 or later were identified by searching BIOSIS Previews, http://www.datastarweb.com, 1996 to date, using the search strategy “(vildagliptin OR laf 237) AND diabetes AND PT=MEETING$ AND LG=EN AND (YEAR=2002 OR YEAR=2003 OR YEAR=2004 OR YEAR=2005).” One record was retrieved. Abstracts from the American Diabetes Association (ADA) Scientific Sessions for 2003–2005 inclusive were searched online at http://scientificsessions.diabetes.org/Abstracts/index.cfm using a text search for the terms “vildagliptin” or “laf 237”. A further 19 abstracts were obtained, one of which was a duplicate of the abstract on BIOSIS (Table 1). The manufacturer supplied citation details for four additional abstracts that were not available on the databases searched, and these four were also included (Table 1). This produced a total of 23 abstracts, of which three were excluded as duplicate presentations of data already published as full papers and a further four were excluded because their main focus was another compound, thus leaving 16 abstracts for inclusion (Table 1). © 2008 Core Medical Publishing Limited