Table 2 | Overview of current therapies for the treatment of type 2 diabetes Vildagliptin | place in therapy review Biguanide (metformin) Insulin secretagogues (sulfonylureas) Fast-acting insulin secretagogues (meglitinides) Thiazolidinediones (glitazones/PPAR- gamma agonists) Alfa-glucosidase inhibitors Insulin Advantages Only agent associated with potential weight loss Modest lowering of lipid levels Improvements in fibrinolysis, inflammatory markers, and endothelial function Prevents development of T2D in patients with IGT Relatively inexpensive Relatively inexpensive Rapid onset and shorter duration of action than SUs due to more physiologically appropriate control of postprandial glucose levels Beneficial effects on cardiovascular risk determinants: cytokines, inflammatory markers, lipids, blood pressure, endothelial function Reduced insulin resistance Can be used in patients with reduced renal function STOP-NIDDM trial demonstrated reduced risk of myocardial infarction with acarbose Delay/prevent the development of T2D Do not cause weight gain No clinically significant drug interactions Ability to achieve tight glycemic control Newer noninjectable formulations becoming available Disadvantages GI adverse effects common – minimized by slow titration Rare risk of lactic acidosis limits its use in contraindicated patients e.g. patients with impaired renal function UK Guidelines (NICE 2002) Recommended as a first-line glucose- lowering therapy in patients whose blood glucose is inadequately controlled using lifestyle intervention alone Drug interactions Weight gain Hypoglycemia – requires self-monitoring of blood glucose by the patient Potential effect on myocardial ischemic preconditioning Drug interactions Weight gain – to a lesser degree than SUs Less risk for hypoglycemia than SUs Cost is higher than SUs More frequent dosing schedule than most agents – must be taken shortly before each meal Weight gain Edema ADA/AHA and FDA recommend that glitazones are not used in patients with advanced heart failure symptoms (class III or IV NYHA classification) Increased risk of edema and cardiac failure in combination with insulin Relatively high cost Less efficacious than other classes Relatively high cost Hypoglycemia Weight gain Daily injections Self-monitoring (cost and convenience) First-line therapy if the patient is not overweight or metformin is not tolerated or contraindicated Use in combination with metformin in overweight or obese patients when glucose control becomes unsatisfactory Offered as combination therapy if unable to take, or if HbA1c remains unsatisfactory with, metformin and insulin secretagogues as combination therapy Offered when inadequate blood glucose control on optimized oral drugs GI adverse effects e.g. abdominal bloating and cramping Acarbose considered as alternative when unable to use other oral drugs ADA, American Diabetes Association; AHA, American Heart Association; GI, gastrointestinal; HbA1c, glycated hemoglobin A1c; IGT, impaired glucose tolerance; NICE, National Institute for Health and Clinical Excellence; NYHA, New York Heart Association; PPAR, peroxisome proliferators-activated receptor; STOP-NIDDM, noninsulin dependent diabetes mellitus; SU, sulfonylurea; T2D, type 2 diabetes. developing, and the progression of, microvascular complications are substantially reduced with intensive blood glucose control (HbA1c approximately 7%) (UKPDS 1998a,b). Most of the commonly used oral glucose-lowering drugs are only able to reduce HbA1c by approximately 1% (Kimmel & Inzucchi 2005). This reduction is not sufficient for patients who have HbA1c levels much greater than the recommended target. Long-term glycemic control is difficult to sustain with oral glucose- lowering drugs. One of the main reasons for the lack of long-term glycemic control with oral medications is that they target the Core Evidence 2008;3(1) tissue abnormalities of the disease (i.e. sensitize specific tissues to the effects of insulin or enhance the insulin-producing activity of the pancreas) rather than treating the underlying causes of these abnormalities, which is the declining function of pancreatic beta cells that results in a reduction in endogenous insulin secretion. Antidiabetic medications are required that can preserve beta-cell function and prevent continuing loss and disease progression. Despite the ability of insulin to achieve tight glycemic control, physicians and people with diabetes are reluctant to use it to treat type 2 diabetes until after the failure of multiple oral glucose-lowering drugs. This is partly due to the burden of 17