Oral Insulin Effective in Type 2 Diabetes

Laurie Barclay, MD

January 31, 2003

Jan. 31, 2003 — A new oral insulin formulation was as effective in controlling blood sugars as injectable regular insulin in a small group of type 2 diabetics, according to the results of a randomized, single-blind study reported in the February issue of Diabetes Care.

"There is strong evidence suggesting that an oral insulin product would provide insulin in a more physiologic manner [than injectable insulin], with a resultant decrease in peripheral insulin concentrations, and that it would more adequately 'insulinize' the liver," write Mark Kipnes, MD, from Diabetes and Glandular Disease Research Associates in San Antonio, Texas, and colleagues.

The investigators enrolled 18 patients with type 2 diabetes in this three-way crossover, dose-escalation study. Each subject received a single dose of each of the following study drugs on three separate days: oral hexyl-insulin monoconjugate 2 (HIM2; 0.375, 0.5, or 1.0 mg/kg), subcutaneous regular insulin (8 units Humulin R), and oral placebo. At 30 minutes after each dose, subjects ingested 16 oz of Boost Plus containing 720 calories, and plasma glucose and insulin concentrations were determined during the four-hour postdose period.

The mean glucose area under the curve for 0 to 240 min (AUC[0-240]) values were lower following administration of 0.5 and 1.0 mg/kg HIM2 vs. placebo (1,097.1 vs. 1,196.9 and 801.1 vs. 992.1 mg/h/dL, respectively). The mean glucose AUC(0-240) values were similar after administration of 0.5 and 1.0 mg/kg HIM2 vs. subcutaneous insulin (1,097.1 vs. 1,048.0 and 801.1 vs. 875.2 mg/h/dL).

Pooled data from the 0.5- and 1.0-mg/kg dose groups suggested that HIM2 and subcutaneous insulin were equivalent in terms of effect on two-hour postprandial glucose concentration, maximum postprandial glucose concentration, and glucose AUC(0-240). However, peripheral insulin concentrations were lower with HIM2 than with subcutaneous insulin (mean insulin AUC(0-240) of 193.1 vs. 233.6 and 230.8 vs. 270.3 micro U/h/mL, respectively).

Oral insulin was safe, well tolerated, more effective than placebo, and as effective as subcutaneous regular insulin at controlling postprandial glycemia, even though peripheral insulin concentrations were lower after the administration of oral insulin compared with subcutaneous insulin.

"Thus, HIM2 therapy may control postprandial glycemia without causing peripheral hyperinsulinemia in patients with type 2 diabetes," the authors write. "The results of this study suggest that oral HIM2 may be useful in patients with type 2 diabetes who experience inadequate postprandial glycemic control."

Nobex Corporation supported this study.

Diabetes Care. 2003;26:421-426

Reviewed by Gary D. Vogin, MD