Potential Diabetes Drug Could Limit Injections to Once a Month

A research team from Duke University has developed a method of providing glucose control that could last for weeks for diabetes patients. It takes only a single injection of the drug by this method to offer this relatively long-term protection, and thus promises to be a boon for diabetics who require insulin injections every few days. The drug is a controlled release formulation that works by increasing the time spent in circulation, and in order to potentially lower the number of doses required every month. The new finding was published in the Journal Nature Biomedical Engineering.

Mechanism of Action:

Earlier methods involved the stimulation of the glucagon-like peptide-1 (GLP1) receptor as a therapeutic strategy for type 2 diabetes.

The advantage of using these molecules is that they regulate the islet hormones and are involved in the feeling of fullness.

However, the disadvantage of this method was that the negative ligand for the GLP1 receptor has

• Enzymatic inactivation that lead to a short half-life
• Fast clearance of the molecule

In order to prolong the effect of GLP1, it was also fused with synthetic microspheres and antibodies, but this only resulted in activity that lasted for 2 to 3 days.

To overcome these limitations, the research team used a single injection of GLP1 that was recombined with elastic like polypeptides that were thermos-sensitive and resulted in

• Slower release
• Circulation period which lasts for about 10 days in mice and 17 days among monkeys

The new method provided

• 10 days of glycemic control among mice
• Reduction in the levels of glycosylated hemoglobin
• Weight gain
• Elimination of peak and valley pharmacokinetics
• Improvement in safety and tolerability

Therapeutic outcomes were, therefore, enhanced by the use of this newly developed mechanism.

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Senior author of the study, Dr. Ashutosh Chilkoti, who is the chair of the Department of Biomedical Engineering (BME) at Duke University, said that the research team had pursued the same method in the past but the current systematic approach, that involved drug delivery using a biopolymer, resulted in longer duration of the drug in the system. The newly developed delivery system tripled the duration of the drug, ranking it better than other drugs used to treat type 2 diabetes.

Dr. Chilkoti further stated that the drugs on account of being synthesized inside E. coli bacterial cultures had lower costs of production which made them cheaper and faster to develop. Such drugs will be a boon in developing countries where cheaper drugs will provide access to many patients with diabetes and faster production will help in catering to the growing demands.

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Also, the drug’s effect on balancing the glucose levels lasted for a period of 10 days after the primary injection, which was better than the previous duration of 2 to 3 days.

Kelli Luginbuhl, co-author of the study said that the most exciting aspect of the study was that the drug could last for a period longer than 2 weeks among non-human primates and since humans had a slower metabolism, they will require only a monthly injection of the drug.

Limitations in The Current Treatment Methods:

Drug Duration: Dulaglutide is the currently used drug for glucose control and it is administered once a week, while standard insulin therapies have to be administered every day.

Human Error: There have been significant strides in therapy to control fluctuating blood sugar levels; however, despite a variety of treatment options, treatment plan is based on frequent, meal-specific dosing. This could give rise to human error. The current study would limit the number of injections that would be required to control blood sugar and could thus lower the risk of human error.

Dr. Chilkoti and Luginbuhl are also working on developing drug delivery systems that are effective in providing long-term relief against pain.

Diabetes is a condition that is characterized by elevated blood sugar levels. Insulin is a hormone that is used to control the rise in glucose levels and some people require an injection to be administered every day. The current study will help in maintaining blood sugar levels for a prolonged period, providing a better therapeutic strategy. In a country like India, which is considered the diabetes capital of the world, this strategy will ease the treatment method of this metabolic syndrome.

References:

1. What is Diabetes? - (https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes)
2. The current state of diabetes mellitus in India - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920109/)

Source-Medindia