Oral basal insulin not yet commercially viable despite good glycemic control
medwireNews: Oral insulin 338 (I338), a long-acting basal insulin analog, provides similar glycemic control to that achieved with insulin glargine (IGlar) among insulin-naive patients with type 2 diabetes, phase II study data show.
In spite of the positive findings, Inge Halberg (Novo Nordisk A/S, Søborg, Denmark) and colleagues report that further development of I338 has been discontinued because “doses were high and, therefore, production of the required quantities of I338 for wide public use was deemed not commercially viable.”
Nonetheless, the results “are expected to encourage the continued development of oral insulin products and to strengthen the aspiration to make oral insulin available to patients with diabetes,” the researchers add.
Halberg and team found that I338, which is formulated in a tablet with the absorption-enhancer sodium caprate, reduced fasting plasma glucose (FPG) concentration from a mean of 9.7 to 7.1 mmol/L after 8 weeks of treatment in 25 insulin-naive adults with type 2 diabetes that was poorly controlled with metformin alone or in combination with other oral antidiabetic drugs.
The reduction was similar to that achieved by the 25 participants randomly assigned to receive IGlar. In this group FPG fell from a mean of 9.1 mmol/L at baseline to 6.8 mmol/L at week 8, resulting in an average difference between the two treatments of 0.3 mmol/L at week 8.
The researchers note that study participants titrated their insulin dose on a weekly basis, with the aim of achieving a self-measured FPG concentration of 4.4–7.0 mmol/L. At the end of the study period, six patients in the I338 group had reached the maximum allowed dose of 16,200 nmol in the I338 group, compared with none reaching the maximum allowed dose of 60 U in the IGlar group.
Both treatments were well tolerated, with no serious adverse events reported in either group. The number of hypoglycemic events was also low, at seven and 11 in the I338 and IGlar groups, respectively.
Writing in The Lancet Diabetes and Endocrinology, Halberg and co-authors say their trial “is the first to show that an oral basal insulin can improve glycaemic 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.”
They conclude: “Additional technological improvements in the area of oral insulin should continuously focus on the biological aspects of addressing the challenges with insulin absorption from the gastrointestinal tract and thereby contribute to reducing the required doses of insulin for oral delivery.”
In an accompanying comment Chantal Mathieu, from KU Leuven in Belgium, says that although the “robust” study opens up “a therapeutic pathway many patients and clinicians had already accepted would never become a reality,” it also reports “a level of variability in achieved glycaemic concentrations that is problematic.”
Indeed, during the last 3 weeks of treatment, total variability in FPG concentration was a significant 90% higher in the I338 group than in the IGlar group according to Halberg et al.
Regardless of the potential problems, Mathieu writes: “The conclusion on the present study should be a positive one: history is being written!
“Oral insulin is a reality and although the present formulation will not be the one taken forward, Halberg and colleagues have blazed a trail and have provided hope for those who need insulin but delay its use because it needs to be injected.”
By Laura Cowen
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