Halberg IB, et al. - In patients with type 2 diabetes, researchers studied the effectiveness and safety of insulin 338 (I338) vs subcutaneous insulin glargine (IGlar). In insulin-naive patients with type 2 diabetes, I338 could safely improve glycemic control without any indication of it differing from insulin glargine, a commonly used subcutaneously administered basal insulin. Further development of this specific oral insulin project was discontinued because the doses of I338 were high and the production of the required quantities of I338 for wide public use was therefore considered not commercially viable. Diarrhea and nasopharyngitis were the most common reported adverse events.

Methods

• It was a phase 2, 8-week, randomized, double-blind, double-dummy, active-controlled, parallel trial.
• This trial was completed at two research institutes in Germany.
• Insulin-naive adult patients with type 2 diabetes, inadequately controlled by metformin monotherapy or in combination with other oral antidiabetic drugs (HbA_1c 7.0–10.0%; BMI 25.0–40.0 kg/m²), were randomly assigned (1:1) to I338 plus subcutaneous placebo once daily (I338 group) or IGlar plus oral placebo once-daily (IGlar group).
• Randomization occurred through an interactive web response system stratified by oral antidiabetic drug treatment.
• Patients and researchers were masked to treatment assignment.
• Weekly insulin dose titration aimed at achieving a self-measured fasting plasma glucose (FPG) concentration of 4.4–7.0 mmol/L.
• The recommended starting daily doses were 2,700 nmol I338 or 10 U IGlar, and maximum allowed doses throughout the trial were 16,200 nmol I338 or 60 U IGlar.
• Treatment difference in FPG concentration at 8 weeks for all randomly assigned patients receiving at least one dose of trial product (ie, the full analysis set) was the primary endpoint.

Results

• Eighty-two patients were screened for eligibility and 50 patients were randomly assigned to the I338 group (n=25) or the IGlar group (n=25) between June 1, 2015 and October 19, 2015.
• Data reported that mean FPG concentration at baseline was 9.7 (SD 2.8) in the I338 group and 9.1 (1.7) in the IGlar group.
• Investigators found that least square mean FPG concentration at 8 weeks was 7.1 mmol/L (95% CI 6.4–7.8) in the I338 group and 6.8 mmol/L (6.5–7.1) in the IGlar group, with no significant treatment difference (0.3 mmol/L [–0.5 to 1.1]; p=0.46).
• Patients tolerated both I338 and IGlar well.
• In 15 (60%) patients in the I338 group and 17 (68%) patients in the IGlar group, adverse events were reported.
• Diarrhea (three [12%] patients in each group) and nasopharyngitis (five [20%] in the I338 group and two [8%] in the IGlar group) were the most common adverse events.
• The majority of adverse events were mild (47 of 68 events), and there were no reported serious adverse events.
• One patient in the IGlar group had a serious adverse event emerging from treatment (urogenital hemorrhage of moderate intensity, assessed by the investigator as unlikely to be related to treatment; the patient recovered).
• In both groups (n=7 events in the I338 group; n=11 in the IGlar group), incidence of hypoglycemia was low, without any serious episodes.