Vildagliptin | place in therapy review multiple daily injections that are associated with poor patient compliance. Therefore, there is a need for oral medications that can achieve similar prolonged glycemic control to that of insulin. Furthermore, the emerging epidemic of type 2 diabetes in children and adolescents presents a new challenge, as this population will have a lifetime risk of complications and may require effective glycemic control over a prolonged period of time. Safety and tolerability Current treatments for type 2 diabetes are also often limited by their contraindications and side-effect profile that may affect patient compliance and quality of life (Table 2). One of the most common side effects with sulfonylureas, thiazolidinediones, and insulin is weight gain. The UKPDS 33 study demonstrated that weight gain was significantly higher (mean 2.9 kg) in patients with type 2 diabetes receiving blood glucose control with sulfonylureas or insulin compared with conventional treatment with diet (P<0.001) (UKPDS 1998a). This is of particular concern given that people with diabetes are often overweight before they commence therapy. Another common side effect of the sulfonylureas and insulin is hypoglycemia. Regular self-monitoring of blood glucose levels by fingertip glucose measurements is required to try and avoid hypoglycemic events. However, this extensive monitoring is inconvenient to the patient and incurs extra costs. Finally, agonists of peroxisome proliferators-activated receptor (PPAR) gamma have been associated with fluid retention and concerns over cardiac failure, and metformin is associated with gastrointestinal intolerance and is contraindicated in patients with renal impairment or poor left ventricular function due to the risk of lactic acidosis. Diabetes prevention An emerging concept is the earlier treatment of glucose control in the prediabetes state. Recent clinical trials have shown that the progression of IGT to type 2 diabetes can be delayed or prevented. These trials demonstrated that in patients with IGT, lifestyle intervention (weight loss and modest exercise), treatment with the weight loss agent orlistat, or treatment with antidiabetic medications (metformin or acarbose) can reduce the risk of developing type 2 diabetes by 25–58% (Pan et al. 1997; Tuomilehto et al. 2001; Chiasson et al. 2002; Knowler et al. 2002; Torgerson et al. 2004). The ADA recommends screening men and women aged ≥45 years, particularly those with a body mass index (BMI) ≥25 kg/m2 every 3 years to detect IGT or IFG (ADA/ NIDDKD 2002). Currently, it is recommended that patients diagnosed with IGT or IFG are given counseling on weight loss and increasing physical activity. The ADA and National Institute of Diabetes, Digestive and Kidney Disease (NIDDKD) have suggested that additional research is required to determine the cost effectiveness of drug therapy as a preventative measure (ADA/NIDDKD 2002). No antidiabetic drugs are currently licensed for use in individuals with prediabetes and existing medications have several disadvantages including unwanted side effects. Therefore, there may be a need 18 for further treatments to delay or prevent the progression of IGT to type 2 diabetes. Addressing unmet need: new classes of antidiabetic medications To address some of these unmet needs in patients with type 2 diabetes, new classes of noninsulin antidiabetic drugs been developed, including the dual PPAR agonists (e.g. muraglitizar, subsequently discontinued), amylin analogs (e.g. pramlintide acetate, an injectable adjunct to insulin), incretin mimetics (GLP-1 analogues), and the DPP-4 inhibitors, that act as incretin enhancers. In addition, a number of alternative methods of delivery of insulin are being studied. Incretin mimetics and DPP-4 inhibitors address the need to act on the underlying disease rather than on its symptoms. They enhance glucose-dependent insulin secretion by pancreatic beta cells, and consequently there is little risk of hypoglycemia. They also suppress elevated glucagon secretion and increase satiety. It has been hypothesized that they may restore beta-cell sensitivity to glucose, which could mean that they may be able to delay the onset of type 2 diabetes, slow its progression, and reduce its cardiovascular and metabolic complications (Holst & Gromada 2004). The GLP-1 analog exenatide (Byetta®; Amylin Pharmaceuticals and Eli Lilly) was the first in this new class of diabetes treatment to be approved by the FDA in June 2005. It is approved as an adjunctive therapy in patients with type 2 diabetes who have not achieved adequate control on metformin and/or a sulfonylurea. All GLP-1 analogs are injectable, which may pose a barrier to their use as many doctors and people with diabetes are reluctant to use injected therapies. A review of the dual-PPAR agonists, amylin analogs, and GLP-1 analogs is beyond the scope of this article, and therefore, these drugs will not be discussed in further detail. DPP-4 inhibitors Vildagliptin (Galvus) is one of a new class of DPP-4 inhibitors that was approved for use in type 2 diabetes in the EU in February 2008. Other DPP-4 inhibitors include sitagliptin phosphate (Januvia®; MRK-0431; Merck Sharp & Dohme/Merck & Co. Inc), which was approved in the US in 2006, and saxagliptin (BMS-477118; Bristol-Myers Squibb). Inhibition of DPP-4 delays the degradation of GLP-1 therefore reducing glycemia, sustaining insulin levels, and reducing glucagon levels in patients with type 2 diabetes (Ahrén et al. 2004b). DPP-4 inhibitors were developed to meet existing unmet needs in the treatment of type 2 diabetes, and an ideal agent would possess the following attributes: good glycemic control, low incidence of hypoglycemia, beta-cell preservation and improvement in beta-cell function, no weight gain, oral route of administration, and good tolerability with minimal gastrointestinal events. One of the main advantages of DPP-4 inhibitors, in contrast to the GLP-1 agonists, will be their mode of administration, which is via the oral route, and may lead to higher levels of adherence to therapy. © 2008 Core Medical Publishing Limited