Review of clinical trials: update on oral insulin spray formulation.

Large clinical trials have shown that improving glycaemic control significantly reduces the risk of long-term microvascular complications in type 1 (T1DM) and type 2 (T2DM) diabetes. Achieving optimal glycaemic control often requires the use of multiple daily insulin injections. Current approaches to insulin administration are less than optimal; many T2DM patients view insulin therapy as inconvenient and uncomfortable and may delay starting insulin therapy because of this. A new oral insulin spray formulation and delivery system provides an alternative to injectable and inhaled insulin. The system allows a liquid oral spray insulin formulation to be delivered into the mouth via an aerosolized spray. The oral insulin spray is a tasteless liquid aerosol mist formulation that is administered to the buccal mucosa using a proprietary delivery system. The active pharmaceutical ingredient is recombinant human insulin; however, the formulation behaves in a fashion more similar to the synthetic fast-acting insulin analogues. In clinical studies of healthy subjects and subjects with T1DM and T2DM, investigators have shown that the oral insulin spray was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action when compared with regular insulin given subcutaneously. In all of the studies conducted, the oral insulin spray was generally well tolerated. Some healthy individuals and subjects with T1DM experienced transient (1-2 min) mild dizziness during dosing; these symptoms were mild and self-limited. No changes in vital signs, laboratory values or physical examination results were noted. The ease of use of the insulin spray formulation may increase patient acceptance and treatment compliance, thereby potentially reducing complications and improving quality of life for patients with insulin-dependent diabetes. This article provides an overview of the safety profile and proposed mechanism of action of this insulin formulation and presents findings from trials which studied its effects in subjects with T1DM and T2DM.