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New Medicines

Oral-lynType 1 and 2 diabetes mellitus


New molecular entity

Development and Regulatory status


Jan 18: Generex have initiated reformulation of Oral-lyn, with a view to reducing the number of sprays required. Company plan to approach FDA to request a fast track pathway through the regulatory process for T2DM [22].

Jan 17: No further development reported [21].

Oct 14: No development or regulatory activity in the EU reported [18].

Mar 15: launched in several minor markets; P3 Eastern Europe but no indication of plans to market in US / EU [17].

Sep 09: The FDA has granted approval for the use of Oral-lyn under the Treatment Investigational New Drug (IND) program. This allows early access to Oral-lyn for patients with serious or life-threatening Type 1 or Type 2 diabetes mellitus who are not eligible to participate in the ongoing PIII study and for which there is no satisfactory alternative treatment [10].

Mar 09: PIII in US for type 1 diabetes and PII in EU for type 2 diabetes (8).

Approved in Ecuador May 05 (6). PIII trials in Canada & EU due to start 05.


Regular human insulin administered to the buccal mucosa using the RapidMist device
In 2011 the UK prevalence of diabetes was 4.45% (about 2.9 million people). It is thought a further 850,000 are undiagnosed. The prevalence is projected to increase to 5 million people by 2025. About 90% of people with diabetes have type 2 disease.
Type 1 and 2 diabetes mellitus

Further information

To be confirmed

Trial or other data

01. Buccal insulin formulation. Promising phase 2 trials (1). Oral spray administration of insulin to 22 pts with NIDDM produced serum insulin levels greater than those achieved in pts taking oral antidiabetics (2). Following a meal challenge in patients with Type I and Type II diabetes, Oralin provided control of post prandial glucose that was similar or better than very rapid acting insulin. After 90 days of administration, Oralin elicited a significant reduction in A1c haemoglobin levels in patients with Type II diabetes failing on oral agents (3). Pivotal PIII trial to start pending US FDA authorisation (4). Positive preliminary results from a single-centre, open-label, active-comparator trial (n=20, single dose or split dose given) (5).
02. Mar 09: A PIII trial in type 1 diabetes started in April 2008 at sites in North America and Eastern Europe (NCT00668850). The aim of the 26 week trial is to compare the efficacy of Oral-lyn™ RapidMist™ System and standard regular human insulin therapy (twice daily NPH) as measured by HbA1c. The plans are to enrol 750 subjects and the estimated completion date is December 2010. A press release in Mar 09 stated: To date, more than 300 subjects have been enrolled, with 60 subjects having achieved the requisite six-month treatment milestone, and the product´s non-inferiority to injectable meal-time (prandial) insulin appears to be maintained. If the current positive trend is maintained, then a large reduction of required enrollment will suffice for formal verification of the non-inferiority hypothesis (9).
03. Dec 09: The article: Review of clinical trials: update on oral insulin spray formulation, was published online this month in advance of print publication in Diabetes, Obesity and Metabolism. The article is available at
04. May 10: Over 400 subjects enrolled in pivotal global Phase III study of Oral-lyn™ (12)
05. Oral-lyn is a liquid formulation of regular human insulin that is administered using Generex´s proprietary Metered Dosage Aerosol Applicator, called RapidMist™, to the buccal mucosa, limiting its absorption to the mouth with no entry to the lungs. Oral-lyn is a prandial insulin and can be administered immediately prior meals in patients with diabetes (13).
06. Dec 10: A paper entitled Buccal spray insulin in subjects with impaired glucose tolerance: the prevoral study has been published in the January 2011 issue of Diabetes, Obesity and Metabolism. In the proof-of-concept study, 31 subjects with IGT, mean age 52 years and BMI 33, received Oral-lyn in equal doses before and 30 minutes after drinking 75 grams of glucose in a standard oral glucose tolerance test. Treatment with an aggregate of 12 sprays resulted in a 29.6% decrease in plasma glucose at 2 hours and a 26.8% decrease at 3 hours. Overall, the study found a mean reduction in glucose levels of 15.8%. Plasma insulin was significantly increased at 30 minutes but not at 2 hours or 3 hours. A second trial (Prevoral 2) is underway where subjects with IGT are being treated for six months with either (a) Oral-lyn + diet and exercise vs diet and exercise alone. The end-point of the Prevoral 2 study is HB1Ac. Final results of the Prevoral 2 study will be available in mid-2011 [14].
07. Jul 11: Preliminary results of two major trials using the Oral-lyn™ formulation that will be used for registration and marketing reported; the 084 trial in patients with T1DM and the Prevoral trial in patients with impaired glucose tolerance. 463 patients completed the 084 study and 31 patients with obesity and IGT completed the Prevoral trial. In summary, Oral-lyn: increased circulating plasma insulin within 30 minutes restoring first phase insulin response; did not raise insulin levels at 2 and 3 hours reducing the potential for post-meal low blood sugar; reduced the rise in blood glucose by 1/3 at 2 hours and 1/4 at 3 hours reducing risks of postprandial hyperglycaemia; significant decreased HbA1c in patients with IGT, and maintained HbA1c levels at baseline values in T1DM patients previously treated with injected insulin; was not associated with serious hypoglycemia or other significant adverse events, body weight changes or development of insulin antibodies [15].
08. July 13: Results from PIII study comparing buccal insulin spray with rapid insulin injection in pts with type 2 diabetes. Oral-lyn significantly lowered the HbA1c at 6 weeks (6.96% vs. 7.42%) and 12 weeks (6.99% vs. 7.24%) compared to baseline (p
09. Aug 15: Generex have engaged the University of Toronto´s Centre for Molecular Design and Pre-formulations to enhance the Generex Oral-lyn formulation to make it more attractive to patients and prospective commercilaization partners by increasing bioavailability of insulin in the product and reducing the number of sprays required to achieve effect prandial metabolic control for patients with diabetes. In dogs given the enhanced formulation there was a 9-fold increase in serum insulin at 15 minutes and almost 500% greater absorption of insulin [19]. There are currently no trials of this new formulation registered in the EU [20].
10. May 18: No clinical trials appear to be ongoing at present [23-25].

Evidence based evaluations