Type 2 diabetes research: fewer side effects from modified medication

Scientists have made progress in the quest to find medication for Type 2 diabetes that causes fewer side effects than current treatments.

Researchers at the University of Pennsylvania and Syracuse University altered the key ingredient in current diabetes drugs, producing a compound that is effective for hyperglycaemia in animal trials, but without the most problematic side effects of current drugs.

The team modified the active ingredient in current drugs, a compound called exendin-4 by attaching each molecule of exendin-4 to vitamin B12. They created a compound that is absorbed to a lesser degree by the dorsal vagal complex region of the brain that triggers nausea and vomiting.

Dr Bart De Jonghe of the University of Pennsylvania School of Nursing, one of the study leaders, said, “Drug regimens often have long lists of side effects which negatively impact treatment. In Type 2 diabetes, nausea and vomiting top that list. It’s the main reason people stop taking their diabetes medications, and diminishes quality of life for millions who do take them.”

As laboratory rats and mice are unable to vomit, the researchers used the musk shrew, a mouse-sized mammal with a vomiting reflex similar to humans.

Using the modified drugs made a striking difference in the shrews’ response. While both versions of the drug provided equal benefits for controlling blood sugar, vomiting occurred in almost 90% of shrews dosed with ordinary exendin-4 and only 12% of shrews treated with the modified version.

The widely prescribed class of drugs mimics the hormone glucagon-like peptide-1 (GLP-1), which controls hyperglycemia. Yet all FDA-approved GLP-1 based drugs cause nausea and vomiting in 20-50% of patients.

Since 1996, the number of people diagnosed with diabetes in the UK has risen from 1.4 million to 3.5 million. And, taking into account the number of people likely to be living with undiagnosed diabetes, the number of people with diabetes in the UK is more than 4 million. This figure is estimated to rise to 5 million by 2025.

Type 2 diabetes, which is linked to obesity, is one of the world’s most common long-term health conditions. It is estimated that 415 million people are living with diabetes globally – around one in 11 of the world’s adult population.

De Jonghe and his collaborators presented their findings at the annual meeting of the Society for the Study of Ingestive Behavior.