News Article
Two Oral Insulins Shown to Lower Blood Sugar in Patients With Type 2 Diabetes
ROME (EGMN) - Two novel oral insulin formulations significantly reduced postprandial glucose levels in studies of patients with type 2 diabetes.
Data on the two oral insulin formulations, Diabetology Ltd.'s Capsulin and Biocon Pharmaceuticals' IN-105, were presented as separate oral abstracts at the annual meeting of the European for the Study of Diabetes.
"Oral insulin has many potential advantages over other forms of insulin delivery, as it most closely mimics the natural insulin secretion pathway from the pancreas to the liver," said Timothy P. Broke-Smith, senior analyst at Diabetology Ltd., Cobham, England.
He reported data on Capsulin, an enteric-coated capsule formulation of unmodified recombinant human insulin with excipients formulated to enhance absorption across the gut wall. It is stable for 18 months at room temperature, and has a bioavailability of about 10% relative to subcutaneous insulin. Absorption occurs in the jejunum and upper small intestine, draining into the mesenteric portal system.
In a phase II study, 16 patients with type 2 diabetes were randomized to either 150 U (5.6 mg) of Capsulin twice daily for 10 consecutive days taken at home approximately 1 hour before breakfast and 1 hour before supper, or 12 U of rapid-acting insulin at the same times. After 10 days, the groups were crossed over. The patients conducted self-monitored blood glucose readings 5 times a day (fasting, 2 hours after breakfast, before dinner, 2 hours after dinner, and at bedtime).
The 12 men and 4 women in the study had a mean age of 60.2 years, mean body mass index of 28.3 kg/m², and baseline hemoglobin A
By day 10, the proportion of post-meal values that fell within the range recommended by the American Diabetes Association (less than 8.9 mmol/L) had increased significantly, from 9.7% on day 2 to 35.5% by day 10. This effect was more pronounced during the evening meals, where the proportion of readings that fell within the recommended range increased from 6.3% on day 2 to 43.8% by day 10, which was highly statistically significant, he reported.
At the same time, significant improvements were seen in HbA
Data on IN-105 were presented by Dr. Harish Iyer, head of research and development at Biocon Ltd., Bangalore, India. Like Capsulin, IN-105 is a conjugated insulin molecule taken orally, with hepatic portal vein delivery. As such, it "behaves very much like first-phase insulin," and could therefore potentially be used concomitantly with oral agents or as the postprandial component of intensive insulin therapy, he said.
In an open-label, placebo-controlled, dose-escalation study, 20 patients with type 2 diabetes were given single doses each of placebo and 10-, 15-, 20-, and 30-mg IN-105 tablets 20 minutes prior to a 600-Kcal breakfast during 5 separate periods. If a patient experienced hypoglycemia at any dose, he or she was not escalated to the next higher dose. There was clear suppression of postprandial glucose with increasing doses, with 2-hour increases from baseline of 94.9 mg/dL with placebo, 79.5 mg/dL with 10 mg, 70.7 mg/dL with 15 mg, 63.5 mg/dL with 20 mg, and 45.3 mg/dL with 30 mg. Suppression of C-peptide continued up to 180 minutes.
Of the 20 patients given the 10-mg dose, postprandial glucose values were less than 180 mg/dL in 6 patients at 1 hour and in 2 patients at 2 hours, with no patients having plasma glucose values below 54 mg/dL. For the 19 patients given 20 mg, 9 and 3 patients, respectively, had glucose values below 180 at 1 hour and 2 hours, again with no patients having hypoglycemia as defined by a value below 54 mg/dL. For the 18 patients given 30 mg, 13 and 6 patients, respectively, had glucose values below 180 at 1 hour and 2 hours, with 2 patients having hypoglycemia as defined by a value below 54 mg/dL.
Only one subject was not escalated because of symptoms of (but not actual) hypoglycemia, while one patient in the 20-mg group withdrew because of high fasting glucose, Dr. Iyer reported.
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