Long-term use of liraglutide - a drug used to lower blood sugar levels in type 2 diabetes patients - may have a deteriorating effect on insulin-producing beta cells, leading to an increase in blood sugar levels, a new study has claimed.
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There is now compelling evidence that liraglutide therapy is efficacious at least in the short term, since it produces an initial reduction in blood sugar. However, many patients do not respond to the treatment and some even display adverse reactions such as nausea, vomiting and diarrhoea.
Researchers from Karolinska Institute in Sweden and University of Miami in US conducted a study on mice implanted with human insulin-producing cells. Blood-sugar suppressors in the form of analogues of the incretin hormone GLP-1 are commonly used in the treatment of type 2 diabetes, since they stimulate the glucose response of the pancreatic beta cells to make them secrete more insulin.
To study the long-term effects of incretin therapy, researchers worked with humanised mice, generated by transplanting human insulin-producing cells into the anterior chamber of the eye. The mice were given daily doses of liraglutide for more than 250 days, during which time the researchers were able to monitor how the pancreatic beta cells were affected.
The results showed an initial improvement in the insulin-producing cells, followed by a gradual exhaustion, with reduced secretion of insulin as a response to glucose. This, they say, was unexpected.
"Given the lack of clinical studies on the long-term effect of these drugs in diabetes patients, this is a very important discovery," said Midhat Abdulreda from University of Miami. "We also need to take these results into account before prescribing blood-sugar suppressing GLP-1 analogues when planning long-term treatment regimens for patients," said Per-Olof Berggren from Karolinska Institute.
"Our study also shows in general how to carry out in vivo studies of the long-term effects of drugs on human insulin-producing cells, which should be extremely important to the drug industry," said Berggren.
The findings were published in the journal Cell Metabolism.