Issue 111 Item 4 ADA: Insulin Patch May Help Dodge the Needle

A 24-hour insulin patch to provide painless, needle-free, basal insulin delivery for people with diabetes coming closer. Avoiding insulin injections would greatly improve quality of life for many diabetics, and new products presented at the American Diabetic Association annual meeting promise to do exactly that. These include insulin in transdermal, oral pills, oral spray, and pulmonary inhaled forms.

"Studies are underway to develop a convenient 24-hour insulin patch to provide painless, needle-free, basal insulin delivery for people with diabetes," write Alan M. Smith and colleagues. "Basal insulin infusion has been achieved using a transdermal patch containing an unmodified approved insulin formulation without the use of chemical enhancers, iontophoresis or ultrasound."

In this pharmacokinetic study, 5 nondiabetic volunteers tested an insulin patch delivery system containing a commercially available insulin lispro formulation in a liquid reservoir patch, creating shallow microscopic pores through the stratum corneum of the volar forearm. Serum lispro levels showed a steady infusion throughout the 12-hour patch application, with decline to baseline in approximately 2 hours. On average, serum insulin lispro levels were maintained above 5 mcU/mL between 1 and 12 hours.

To complement the basal insulin patch, diabetics could take orally absorbed insulin in a pill with maximal effect at 30-50 minutes.

"Oral administration of capsules containing the insulin/[Emisphere] delivery agent combination provides insulin absorption at clinically significant levels," write Richat Abbas and colleagues from Emisphere Technologies Inc. in Tarrytown, N.Y.

In this pharmacokinetic and pharmacodynamic study of human insulin after oral administration in 29 healthy subjects, insulin was rapidly absorbed into the systemic circulation, and plasma concentrations peaked within 25 minutes. Corresponding maximum reductions in both plasma glucose and C-peptide concentrations occurred within 1 hour. Insulin alone or the Emisphere delivery agent alone given orally did not affect plasma insulin or glucose levels. The most common adverse event was hypoglycemia, but there were no serious adverse events, and all doses were well tolerated.

A similar study by Miriam Kidron and colleagues from Hadassah-Hebrew University Medical Center in Jerusalem also showed that oral dosing of insulin using the Emisphere oral delivery agent appears to be practical.

"Much effort and research have been invested in finding alternative routes of insulin administration, namely, nasal, dermal, pulmonary, and oral," they write. "The combination of insulin and an Emisphere delivery agent enables the absorption of insulin from the gastrointestinal tract."

In 12 nondiabetic volunteers, nadir of plasma glucose occurred 30-50 minutes after the oral dose, suggesting that the absorption site is in the upper part of the gastro-intestinal tract, most likely the duodenum. Plasma C-peptide levels decreased with increased amounts of exogenous insulin absorbed, suggesting suppression of secretion of endogenous hormone. With higher oral insulin doses, blood glucose and C-peptide levels decreased by 50%. There were no adverse effects detected during the study or up to 12 weeks later. ADA Annual Meeting: Abstracts 197-OR, 526-P, 191-OR. June 15-16, 2002.