AT THE ADA ANNUAL SCIENTIFIC SESSIONS

SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).

“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.

According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.

In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.

Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A1c (HbA1c) levels between 7% and 10%.

The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.

The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.

Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA1c, and fructosamine levels at 8 weeks.

Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.

In a post hoc analysis, mean HbA1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.

In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)

was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.

“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.

Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.

endonews@frontlinemedcom.com

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