Novel compound could treat type 2 diabetes without common side effects
Posted: 24 June 2020 | Victoria Rees (Drug Target Review) | No comments yet
Two molecules combined into a new substance to treat type 2 diabetes lowered blood sugar in shrew models without causing nausea, vomiting and weight loss.
A new drug lead to treat type 2 diabetes without the common side effects of other drugs has been developed. Syracuse University, US, chemistry professor Dr Robert Doyle and collaborators combined two molecules into a new substance that lowers blood sugar without causing feelings of nausea, vomiting and undesired weight loss.
The team developed a novel method of bioconjugation, a chemical technique used to join two molecules together. By binding exendin-4 (Ex4), a US Food and Drug Administration (FDA)-approved glucagon-like peptide-1 receptor (GLP-1R) agonist, to dicyanocobinamide (Cbi), which is a small piece of the complex vitamin B12 molecule, the researchers produced Cbi-Ex4 in a technique they call ‘corrination’.
Data collected from testing Cbi-Ex4 in the musk shrew (Suncus murinus) revealed beneficial effects as evidenced by improved blood sugar levels during glucose tolerance tests and a profound reduction in vomiting compared to Ex4 alone. Importantly, no weight loss was noted, again in stark contrast to the currently approved GLP-1R agonist, making this new drug ideal for patients who require glucoregulation without affecting their body mass index (BMI) levels.
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The team say this drug could therefore benefit diabetic patients who also live with cystic fibrosis, chronic obstructive pulmonary disease (COPD), sarcopenia, cancer or HIV, where weight-loss is counter-indicated.
The next step in the development of this groundbreaking drug is to move it through the pre-clinical phase into Phase I human studies. Doyle and his team have submitted a new grant proposal to the US National Institutes of Health (NIH) to fund this effort.
“There’s no treatment out there now that can keep weight off for a long period of time without illness behaviours such as nausea,” Doyle said. “So, my group is pushing to expand on GLP-1R agonists to treat diabetes with obesity and… to treat diabetes without affecting nutritional status.”
The article is published in Cell Reports.
Related topics
Drug Discovery, Drug Leads, Drug Targets, Hit-to-Lead, Research & Development, Therapeutics
Related conditions
Diabetes, Type-2 diabetes
Related organisations
Syracuse University, US Food and Drug Administration (FDA), US National Institutes of Health (NIH)
Related people
Dr Robert Doyle
