Miriam E Tucker

June 28, 2017

SAN DIEGO — An oral basal insulin formulation has produced glycemic control equivalent to that of injected insulin glargine in insulin-naïve type 2 diabetes patients.

Results from a phase 2a Novo Nordisk–sponsored feasibility study were presented on June 13 here at the American Diabetes Association (ADA) 2017 Scientific Sessions by Leona Plum-Mörschel, PD, chief executive officer of Profil Mainz, Germany.

The abstract was among just eight selected for presentation in the ADA President's Oral Session on the last day of the conference.

"After almost 100 years of oral insulin research, this trial demonstrates for the first time that an oral basal insulin can safely improve glycemic control in patients with type 2 diabetes," Dr Plum-Mörschel said in her presentation.

The enteric-coated tablets used in the study were designed to deliver insulin to the duodenum, where it is released along with an absorption enhancer to increase bioavailability, she explained.

Asked to comment, session moderator Alvin C Powers, MD, director of the division of diabetes and endocrinology, Vanderbilt University School of Medicine, Nashville, Tennessee, who is also president, medicine and science, of the American Diabetes Association, told Medscape Medical News, "Oral insulin has been tried for many years, so this is encouraging that there seems to be bioavailable insulin delivered orally."

However, he cautioned, "I think its comparison to subcutaneous insulin needs more work. It's a very preliminary study, but encouraging in the first trial.…It would be a useful advance if you could give oral insulin to replace the basal in type 2 diabetes."

In fact, Novo Nordisk has discontinued the formulation used in this trial because it required too high a dose to be marketable. But the company is continuing to pursue the technology; Dr Plum-Mörschel told Medscape Medical News that she is "very confident" it will eventually be successful.

Equivalent to Glargine

The phase 2 study enrolled 50 patients with type 2 diabetes who were inadequately controlled (HbA1c 7%–10%) on metformin with or without other oral agents but not insulin.

They were randomized to either the oral insulin or glargine once daily for 8 weeks in a "double-dummy" blinded fashion, so each received both an injection and three tablets, of which one formulation was the insulin and the other a carrier substance. The subjects continued to take metformin and some also were taking dipeptidyl peptidase-4 (DPP-4) inhibitors, but other oral agents were stopped.

At 8 weeks, the primary end point of fasting plasma glucose had dropped significantly in both groups, from 175 mg/dL at baseline to 129 mg/dL in the oral insulin group, compared with 164 mg/dL to 121 mg/dL with glargine, producing an insignificant 5.2-mg/dL difference between the two treatment groups (= .46).

HbA1c also dropped in both groups, from 8.1% to 7.3% with oral insulin and 8.2% to 7.1% for glargine. That treatment difference of 0.3 percentage points was also not significant (= .077).

Decreases in both fructosamine — a shorter-term measure of overall glycemia than HbA1c — and fasting C-peptide were also not significantly different between the two groups (= 0.37 and 0.68, respectively).   

Hypoglycemia was infrequent in both groups, with seven events among six oral insulin patients and 11 events in six glargine recipients. There were no serious hypoglycemic events. Other adverse-event rates didn't differ between the two arms, Dr Plum-Mörschel reported.

And no differences were seen in either body weight or antibody formation, she added in response to audience questions following her presentation. But she noted that those might not become evident in a study lasting just 8 weeks.

The study was funded by Novo Nordisk. Dr Plum-Mörschel has no relevant financial relationships; disclosures for the coauthors are listed in the abstract. Dr Powers has no relevant financial relationships.  

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American Diabetes Association 2017 Scientific Sessions. June 13, 2017; San Diego, California. Abstract 380-OR


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