However, in 2016, Novo Nordisk halted the development of their basal oral insulin tablet.
An oral insulin formulation has been a desirable product among patients and healthcare providers because the ease of administration would increase medication compliance. It would also allow patients with type 2 diabetes to initiate insulin earlier in their disease to gain quicker glycemic control. However, low bioavailability of insulin in an oral formulation has made it difficult to produce adequate plasma concentrations. One drug company, Novo Nordisk, has been developing an oral insulin formulation, OI338GT, in GIPET I tablet technology. The GIPET technology uses absorption enhancers to increase the plasma concentrations of insulin.
Researchers of Novo Nordisk presented their research at the ADA 77th Scientific Session on the safety and efficacy of OI338GT compared to injectable insulin glargine. Participants with type 2 diabetes who were included in the study were insulin naïve and uncontrolled on metformin alone or in combination with other oral antidiabetic medications. 50 participants were enrolled in the phase 2a double-blind, double dummy study for 8 weeks. They were randomized in a 1:1 ratio. 25 participants received once-daily oral OI338GT and a placebo injection while the remaining 25 participants received insulin glargine U100 and a placebo oral tablet. The study groups were titrated up to achieve target fasting blood glucose levels between 80 and 126 mg/dL. Baseline characteristics between the two study groups were similar and the primary outcome, improvement of glycemic control, was measured by a change in fasting blood glucose levels from baseline to week 8. Other outcomes of interest included HbA1c, fructosamine, c-peptide and rate of adverse effects.
Using a linear mixed model for repeated measurements, the results indicated oral insulin was as efficacious as insulin glargine in lowering fasting blood glucose levels [Treatment Difference = 5.2 mg/dL (95%CI: -8.8 to 19.1) p = 0.4567]. Participants treated with oral insulin had similar decrease in average HbA1c from baseline (8.1% vs. 8.2%) to week 8 (7.3% vs. 7.1%) compared to placebo [Treatment Difference = 0.30% (95% CI: -0.33 to 0.63) p = 0.0774]. Fructosamine (p = 0.3700) and fasting c-peptide (p = 0.6799) were also reduced similarly between the two groups. There was no difference in the number of treatment emergent hypoglycemia between the two study groups and no events of severe hypoglycemia were reported.
This study proves it is feasible to formulate an oral insulin tablet with comparable efficacy to injectable insulin. Novo Nordisk has unfortunately stopped further development and research of OI338GT until technological advances can make this product commercially viable in large scale manufacturing. The biggest issue is the low bioavailability, which requires large amounts of the medication to produce adequate plasma concentration levels. However, other companies, such as Oramed Pharmaceutical, are also researching and developing their own oral insulin formulation (ORMD-0801). Therefore, it is still possible to see an oral formulation come into the market in a few years.
- OG338GT, an oral insulin tablet, is just as efficacious in lowering fasting blood glucose and HbA1c levels as insulin glargine injections.
- Novo Nordisk, manufacturer of OG338GT, has stopped further development and research because a large scale manufacturing of their product would not be commercially viable.
- Oral insulin formulations may still be available in the upcoming years due to continued research and development from various pharmaceutical companies.
American Diabetes Association. Daily, Long-Acting Oral Insulin Tablet Provides Comparable Glycemic Control to Insulin Glargine Injection in Patients with Type 2 Diabetes. Press Release. Available at: http://www.diabetes.org/newsroom/press-releases/2017/wassermann-scientific-sessions-2017.html. Accessed June 21, 2017.
McConaghie, Andrew. Pharmphorum. Oral insulin could still be a reality, says Novo Nordisk. News. Available at: https://pharmaphorum.com/news/oral-insulin-still-reality-says-novo-nordisk/. Accessed June 21, 2017.
Joanna Martinez-Mendez, PharmD Candidate 2018, Lake Erie College of Osteopathic Medicine School of Pharmacy: FL Campus