In the Journals

Oral insulin lowers FPG in insulin-naive, type 2 diabetes

Among insulin-naive adults with type 2 diabetes, treatment with a high dose of oral insulin for 8 weeks lowered fasting plasma glucose at a rate comparable with participants assigned to insulin glargine, with no serious adverse events and a low incidence of hypoglycemia, according to findings from a phase 2 study.

Several factors complicate the absorption of protein and peptide drugs, including insulin, from the gastrointestinal tract after oral administration, Inge Birk Halberg, DMD, PhD, MSc, principal clinical pharmacologist at Novo Nordisk in Søborg, Denmark, and colleagues wrote in the study background. Such drugs are susceptible to degradation by proteases in the stomach and intestine, they wrote, and the large molecular size and hydrophilic characteristics of oral insulin therapy can hinder its passage across the epithelium.

“This trial is the first to show that an oral basal insulin can improve glycemic control in patients with type 2 diabetes with a similar safety profile, with no evidence of a difference compared with an established subcutaneously administered basal insulin,” Halberg told Endocrine Today. “The potential benefits of oral basal insulin therapy vs other treatment options still need to be investigated in adequately powered, long-term clinical trials in various patient populations with diabetes.”In a randomized, double-blind, double-dummy, parallel trial, researchers analyzed data from 50 adults with type 2 diabetes who were insulin-naive with a poor glycemic response with metformin monotherapy or combined oral antidiabetes drugs. Researchers randomly assigned participants once-daily oral insulin plus a subcutaneous placebo (n = 25) or once-daily insulin glargine (Lantus, Sanofi) plus an oral placebo (n = 25). Researchers titrated doses weekly to achieve a self-measured FPG between 4.4 mmol/L and 7 mmol/L; recommended starting doses were 2,700 nmol for oral insulin and 10 U of insulin glargine. Primary endpoint was treatment difference in FPG concentration at 8 weeks for all randomly assigned patients receiving at least one dose of trial product.

At baseline, mean FPG was 9.7 mmol/L for the oral insulin group and 9.1 mmol/L for the insulin glargine group.

At 8 weeks, least square mean FPG concentration was 7.1 mmol/L for the oral insulin group and 6.8 mmol/L in the insulin glargine group, with no between-group treatment difference (P = .46), according to researchers.

Most adverse events were mild; no severe adverse events were reported. Incidence of hypoglycemia was low in both groups, with seven events in the oral insulin group and 11 in the insulin glargine group, according to researchers.

The researchers noted that further development of the oral insulin therapy used in this trial was discontinued because doses were high and production of the required quantities of the drug for wide public use was deemed not commercially viable.

“The success of future oral insulin products is not only dependent on the design of an optimal insulin analogue for the purpose of oral delivery, but also on additional technological improvements pertinent to product manufacturing efficiency and relative bioefficacy of the required oral insulin doses when compared with subcutaneously administered insulin,” Halberg said. “The findings are likely to encourage the further development of oral insulin products to the benefit of patients with diabetes.” – by Regina Schaffer

For more information:

Inge Birk Halberg, DMD, PhD, MSc, can be reached at Novo Nordisk A/S, Vandtårnsvej 108-110, DK-2860 Søborg, Denmark; email: ibh@novonordisk.com.

Disclosures: Novo Nordisk funded this trial and was responsible for data interpretation and report writing. All authors are employees and shareholders of Novo Nordisk.

Among insulin-naive adults with type 2 diabetes, treatment with a high dose of oral insulin for 8 weeks lowered fasting plasma glucose at a rate comparable with participants assigned to insulin glargine, with no serious adverse events and a low incidence of hypoglycemia, according to findings from a phase 2 study.

Several factors complicate the absorption of protein and peptide drugs, including insulin, from the gastrointestinal tract after oral administration, Inge Birk Halberg, DMD, PhD, MSc, principal clinical pharmacologist at Novo Nordisk in Søborg, Denmark, and colleagues wrote in the study background. Such drugs are susceptible to degradation by proteases in the stomach and intestine, they wrote, and the large molecular size and hydrophilic characteristics of oral insulin therapy can hinder its passage across the epithelium.

“This trial is the first to show that an oral basal insulin can improve glycemic control in patients with type 2 diabetes with a similar safety profile, with no evidence of a difference compared with an established subcutaneously administered basal insulin,” Halberg told Endocrine Today. “The potential benefits of oral basal insulin therapy vs other treatment options still need to be investigated in adequately powered, long-term clinical trials in various patient populations with diabetes.”In a randomized, double-blind, double-dummy, parallel trial, researchers analyzed data from 50 adults with type 2 diabetes who were insulin-naive with a poor glycemic response with metformin monotherapy or combined oral antidiabetes drugs. Researchers randomly assigned participants once-daily oral insulin plus a subcutaneous placebo (n = 25) or once-daily insulin glargine (Lantus, Sanofi) plus an oral placebo (n = 25). Researchers titrated doses weekly to achieve a self-measured FPG between 4.4 mmol/L and 7 mmol/L; recommended starting doses were 2,700 nmol for oral insulin and 10 U of insulin glargine. Primary endpoint was treatment difference in FPG concentration at 8 weeks for all randomly assigned patients receiving at least one dose of trial product.

At baseline, mean FPG was 9.7 mmol/L for the oral insulin group and 9.1 mmol/L for the insulin glargine group.

At 8 weeks, least square mean FPG concentration was 7.1 mmol/L for the oral insulin group and 6.8 mmol/L in the insulin glargine group, with no between-group treatment difference (P = .46), according to researchers.

Most adverse events were mild; no severe adverse events were reported. Incidence of hypoglycemia was low in both groups, with seven events in the oral insulin group and 11 in the insulin glargine group, according to researchers.

The researchers noted that further development of the oral insulin therapy used in this trial was discontinued because doses were high and production of the required quantities of the drug for wide public use was deemed not commercially viable.

“The success of future oral insulin products is not only dependent on the design of an optimal insulin analogue for the purpose of oral delivery, but also on additional technological improvements pertinent to product manufacturing efficiency and relative bioefficacy of the required oral insulin doses when compared with subcutaneously administered insulin,” Halberg said. “The findings are likely to encourage the further development of oral insulin products to the benefit of patients with diabetes.” – by Regina Schaffer

For more information:

Inge Birk Halberg, DMD, PhD, MSc, can be reached at Novo Nordisk A/S, Vandtårnsvej 108-110, DK-2860 Søborg, Denmark; email: ibh@novonordisk.com.

Disclosures: Novo Nordisk funded this trial and was responsible for data interpretation and report writing. All authors are employees and shareholders of Novo Nordisk.