Do we need new drugs for the treatment of type 2 diabetes mellitus?

At this moment, approximately ten different classes of drugs are or soon will become available for the treatment of type 2 diabetes mellitus (table 1). Of the glucoselowering agents, pramlintide has not been approved by the European Medicines Agency (EMEA) and two, a GLP (glucagon-like peptide)-1 and a DPP (dipeptidyl peptidase)IV-inhibitor, have recently been approved but have not yet become available on the European market. The recent increase in available blood glucose-lowering drugs is remarkable, because after the introduction of insulin (at the beginning of the 20th century), the sulphonylureas and metformin (mid-1940s and 1950s) no innovative treatment modalities had been introduced until less than a decade ago. The development of new classes of glucose-lowering medications has expanded the treatment options for type 2 diabetes, but has also introduced more uncertainty regarding which treatment option is the most appropriate. Recently, management guidelines have been published that provide a directive for the most appropriate intervention for treating patients with type 2 diabetes. Nevertheless, except for the initial therapy, these reports acknowledge that in fact no definitive guidelines can be provided regarding subsequent treatment choices. The primary goal is achieving glucose levels as close to normal as possible without imposing a high risk of (severe) hypoglycaemic attacks. An HbA1c ≥7% should serve as a call to act by initiating or changing therapy to ultimately reduce microvascular and most likely macrovascular complications in type 2 diabetes. Since durability and long-term safety have to be established in almost all new drugs, metformin is universally considered to be the drug of choice as it is cheap, safe and effective. Moreover, metformin is associated with either weight stability or weight loss. As type 2 diabetes is characterised by a progressive decline in β-cell function, treatment needs to be adjusted regularly and commonly results in combination therapy of metformin with sulphonylureas or insulin as secondline treatment; both are cheap and cause effective glucose lowering yet often at the expense of weight gain and a higher risk of hypoglycaemia. Some view the failure of clinicians and their patients to effectively implement available interventions as the main reason for insufficient glycaemic control, more so than the lack of available drugs. So, why do we need new drugs for the treatment of type 2 diabetes if the old ones are so effective?