Prandial insulin: is inhaled enough?

Abstract

The low proportion of patients achieving glycemic targets is well documented for both type 1 and type 2 diabetes. Postprandial glucose levels are often not monitored but contribute significantly to total glycemic burden. Prandial rapid-acting insulin analogues were introduced to address some of these problems but still do not provide a physiologic insulin replacement. Inhaled prandial insulins have been developed to free patients from multiple mealtime injections and make intensive insulin regimens more acceptable. Several inhaled formulations of prandial insulin are in development but differ significantly with respect to inhaler characteristics and pharmacokinetic profiles. This brief review summarizes the properties of the new prandial inhaled insulins and discusses how postprandial glycemic control is dependent not only on the insulin dose, but also on the pharmacokinetic characteristics of insulin delivery. There is no antihyperglycemic agent with a glucose-lowering effect superior to that of insulin; new prandial products that improve coordination between insulin availability and meal absorption and are more acceptable to patients may increase the proportion of diabetic patients achieving and maintaining glycemic targets. Drug Dev Res 69: 138-142, 2008. r2008 Wiley-Liss, Inc.

Pharmacokinetic Characterization of the Novel Pulmonary Delivery Excipient Fumaryl Diketopiperazine

“…2,3 This technology can accommodate therapeutics over a wide molecular size range 1 and has been used to administer insulin and glucagon-like peptide-1 by the pulmonary route in clinical studies. 3,4 A number of other agents, including oxyntomodulin and peptide YY, have been administered in nonclinical studies. 5 Therapeutics administered via the Technosphere technology demonstrate rapid absorption, believed to be associated with rapid dissolution of the microparticles rather than any FDKP-mediated absorption enhancement.…”

Inhaled Insulin: A Breath of Fresh Air? A Review of Inhaled Insulin

“…Benefits included electronic controls guiding the user to inhale the insulin in a reproducible fashion and a breathing pattern for optimal insulin deposition in the lung. 1 It also had the capability to download device information such as dose, frequency, and inhalation patterns. 15 However, the device was also large and required refrigeration.…”

“…15 However, the device was also large and required refrigeration. 1 The AIR insulin formulation used a mechanical inhaler for the dry powder formulation. The particles were significantly larger (5-30 μm) geometrically, although still delivered to the alveolar space due to significantly lower density (o5 μm in aerodynamic diameter due to porous properties).…”

“…However, these formulations continue to fall short of physiologic needs to control postprandial hyperglycemia, with delayed onset of action and prolonged effects leading to excessive hyperglycemia after eating and delayed hypoglycemia. 1 The importance of tight glycemic control has been shown to prevent and/or delay longterm complications of diabetes. 2 The success of insulin therapy, however, depends on its physiologic properties as well as on its proper use.…”

Evaluation of novel particles as an inhalation system for GLP‐1

“…Drugs administered as Technosphere powder demonstrate rapid absorption profiles comparable with intravenous injection [25]. Insulin administered as Technosphere® Insulin is an ultra rapid-acting insulin with the potential to provide clinical benefits for diabetes treatment [16,[25][26][27][28][29][30]. Using this technology platform, GLP-1 Technosphere formulations were prepared by adsorbing GLP-1 onto preformed Technosphere particles.…”