There are novel agents in the pipeline for diabetes

In the next few years, the treatment of diabetes may change dramatically. If just some of the drugs in phase III trials fulfill their current promise and reach market, we may see the following developments:

Pinch yourself. These things are really happening in diabetes therapy-and happening fast.

For years, patients with diabetes and the clinicians who treat them have agreed that the biggest drawback to starting insulin therapy was the accompanying needle. For at least some patients, that is likely to change soon. On Sept. 8, a Food & Drug Administration advisory committee recommended approval of Exubera (insulin [rDNA origin] powder for oral inhalation). The Sanofi-Aventis group and Pfizer Inc. are developing Exubera jointly. Although the FDA is not bound by the recommendations of the advisory committee, recommendations are usually followed, and Exubera will likely be approved in the very immediate future.

Exubera has been evaluated in more than 3,500 patients-some for over seven years-and has been found to have efficacy comparable to injected insulin. Pfizer and Sanofi-Aventis are seeking approval for its use in the treatment of adult patients with Type 1 and Type 2 diabetes, but not children, and not smokers (so far, clinical trials have excluded smokers and people with underlying lung disease). However, data show Exubera does not compromise healthy lung function. A pooled analysis of two one-year open-label studies involving 627 patients with Type 2 diabetes found patients who added Exubera to their treatment regimen experienced no clinically important effects on pulmonary function compared with patients treated solely with oral agents.

Exubera is designed to be inhaled through the mouth into the lungs using a proprietary inhalation device and powdered insulin formulation developed by Nektar Therapeutics. It is quickly absorbed, mimicking the action of physiological insulin in reducing postprandial blood sugar spiking.

Following close on the heels of Exubera is another inhaled insulin formulation that headed into phase III trials in mid-July: Lilly's formulation of human insulin inhalation powder (HIIP) based on Alkermes' AIR pulmonary drug delivery technology. Phase II results (released at the 41st Annual Meeting of the European Association for the Study of Diabetes, held in Athens in mid-September) showed that patients using the Lilly/Alkermes inhaled insulin system achieved blood sugar levels similar to those of patients treated with injected insulin, a hemoglobin A1c of 7.9 compared with 8.0 in the injected insulin group. Eighty percent of patients in the study also preferred the Lilly/Alkermes inhaled insulin system at mealtime to injected insulin.

The new world of diabetes options is also likely to be accompanied by several "incretin enhancers." The basis for interest in incretin enhancers, according to Michelle A. Baron, M.D., FACE, senior medical director, Novartis Pharmaceuticals, was the observation that an oral glucose load triggers a greater insulin response than the same glucose load given intravenously-meaning that something in the gut modulates the insulin response. Investigators have found several incretins that are responsible for what has been termed the "incretin effect." One that has proven particularly interesting to pharmaceutical companies is glucagon-like peptide-1 (GLP-1). Novartis decided to enhance incretin by developing an inhibitor for dipeptidyl peptidase-4 (DPP-IV), the enzyme that breaks GLP-1 down; the company developed vildagliptin (LAF237). Vildagliptin, which is administered orally, is currently in phase III trials.