Abstract
Research Objective: To explore which insulin formulations and which regime is the most effective at achieving normoglycaemia in Type II Diabetes Mellitus in patients who are inadequately controlled with maximal oral glucose-lowering therapy? Background to Research: The United Kingdom Prospective Diabetes Study (UKPDS) highlighted the progressive nature of type II diabetes, showing that a substantial proportion of patients will eventually go on to require insulin to achieve their glycaemic target. It also helped to establish the benefits of tight glycaemic control in terms of reductions in rates of complications. In the UK, about 20-25% of type II diabetics are estimated to require insulin within 10 years of diagnosis and it is acknowledged that a greater proportion would probably benefit. In the US, approximately 30-40% of type II diabetics are currently receiving insulin. In recent years, the number of formulations available for use has increased with the introduction of the rapid acting insulin analogues lispro (Humalog) and as part (Novorapid), and the first soluble long-acting analogue, glargine (Lantus). Increased choice has increased speculation as to what is the most efficacious regime. There is currently no consensus as to which formulations or what regime to use. Recent guidance from the National Institute of Clinical Excellence (NICE) asserts "there is no direct evidence to support the use/choice of any one insulin type or regime over another." There is also uncertainty as to how to most appropriately combine insulin therapy with oral glucose-lowering therapy. The aim of this research is therefore to ascertain what evidence exists supporting the use of various formulations/regimes, what are the advantages and disadvantages of each preparation, and what is the most appropriate way of combining insulin therapy with oral therapy. Methodology I shall conduct a literature review looking for randomised controlled trials and meta-analysis of studies exploring the use of insulin in type II diabetes. All formulations, all regimes and all combinations with oral agents shall be included (acknowledging that combining glitazones with insulin is not currently licensed in the UK). I shall use Medline and EMBASE to identify relevant published papers (restricting myself to English language papers). I shall also seek relevant clinical guidelines from professional bodies (such as NICE and the American Diabetes Association) to ascertain their current recommendations and to review literature that they reference. I shall also approach the key pharmaceutical companies in this therapeutic area including Eli Lilly, Aventis and Novo Nordisk in order to attempt to obtain unpublished research in this field. Anticipated difficulties given the recent NICE guidance proclaiming no direct evidence to support the use of one insulin type or regime over another, I expect that there will be insufficient available information to enable absolute evidence-based conclusions to be drawn. Furthermore, I expect that the pharmaceutical companies may not be overly forthcoming in providing me with their unpublished studies.