What's New in Insulins and Delivery Systems : Intranasal, buccal, oral, peritoneal, and even rectal insulins are in various stages of development.

Altea Therapeutics Corp.'s PassPort is a transdermal insulin delivery system. The patient applies a proprietary patch on the skin, presses an attached button to create micropores, then slaps an insulin-containing patch over the site. Studies indicate that the system provides protracted availability of basal insulin with resultant plasma insulin levels that are proportionate to the various insulin concentrations available in the patch reservoir.

Valeritas Inc.'s insulin device V-Go consists of a small, patchlike insulin pump that contains no electronic components. The disposable skin patch lasts 24 hours, during which it provides basal insulin at a steady rate. The patient can push a small button to release a few extra units of insulin at a time, as a premeal bolus. In addition, Sanofi-Aventis has a very long-acting insulin analogue in phase I studies, and Eli Lilly has a new basal insulin in phase I as well.

▸ New rapid-acting prandial insulins. Development of such products would help to control the daunting problem of postprandial hyperglycemia. One possible solution is Becton, Dickinson & Co.'s device for intradermal injection of insulin lispro, which capitalizes on the fact that insulin is consistently absorbed more rapidly intradermally than subcutaneously. The Becton, Dickinson device consists of a skin patch containing an array of tiny intradermal needles, each of which is no longer than the E in the “E Pluribus Unum” on the back of a penny.

Yet another intradermal insulin product in development is Debiotech SA's Jewel micropump, which is mounted to a disposable skin patch. The system, which is considerably smaller than a fingertip, is now under FDA review.

▸ Ultrarapid-acting insulins. Afrezza is one. The DiaPort system for intraperitoneal delivery is another ultrarapid-acting solution. Yet another is Biodel Inc.'s VIAject, which comprises insulin with ethylenediaminetetraacetic acid and citric acid that forms rapidly absorbed monomers upon subcutaneous injection. In a 16-patient crossover study, peak insulin concentrations were achieved in 34 minutes with VIAject, compared with 63 minutes for insulin lispro and 139 minutes for regular human insulin.

Whether that's quick enough to make for a commercial success remains to be seen, Dr. Skyler said. VIAject is now in phase III testing.

Halozyme Therapeutics' insulin-PH20 technology combines currently available mealtime insulins with recombinant human PH20 hyaluronidase, which results in greatly accelerated insulin action.

▸ Buccal insulin. “The buccal route has been argued about for many, many years,” Dr. Skyler observed. One device for buccal administration that has drawn research and commercial attention recently (Diabetes Obes. Metab. 2010;12:91–6) is Generex Biotechnology Corp.'s Oral-lyn insulin spray, an aerosolized aqueous solution of regular human insulin. The device delivers 10 units per puff to the oral cavity at a velocity of 100 mph. Oral-lyn is marketed only in Ecuador, which Dr. Skyler considers a less-than-ringing endorsement.

▸ “Smart” insulins. Insulin with a built-in glucose sensor was first proposed in the 1970s. The concept is to harness an insulin polymer conjugate to a multivalent glucose-binding molecule. Upon contact with blood glucose, the glucose displaces the insulin in the polymer, freeing the insulin to go into the circulation.

“I'd be quite thrilled to see this kind of insulin come to the market, but I'm a bit skeptical,” Dr. Skyler said.

Dr. Skyler disclosed that he has served as a consultant to and/or received research grants from numerous pharmaceutical companies.