In a new study, a team of researchers from the Karolinska Institutet in Sweden and the University of Miami in Florida analyzed the effects of treatment with analogues of the incretin hormone GLP-1 — drugs commonly used to treat type 2 diabetes — in a humanized mouse (a mouse in which genes, tissues, or even organs are of human origin), and found that extended daily use of these types of drugs — especially liraglutide — are associated with decreased insulin release and increased blood glucose levels.
The research article, “Liraglutide Compromises Pancreatic β Cell Function in a Humanized Mouse Model,” was published in the journal Cell Metabolism.
Incretin mimetics are blood-sugar suppressor drugs frequently used in the treatment of type 2 diabetes, due to their ability to increase the release of insulin through the stimulation of the glucose response of insulin-producing pancreatic beta cells.
There is significant short-term evidence that these drugs, such as liraglutide, are effective at least initially in the control of blood sugar. However, there have been several recent reports detailing side effects such as nausea and vomiting, and also lack of response to treatment. Importantly, the clinical evidence regarding long-term use of these drugs remains scarce.
The research team developed a humanized mouse model transplanted with human insulin-producing pancreatic cells, and studied the effects of the prolonged use of liraglutide. The mice were treated daily with liraglutide for more than 250 days, and researchers monitored the effects on the pancreatic beta cells.
The results showed that although the drug initially had a beneficial function on pancreatic cells, its long-term use compromised the release of insulin and led to an increase in blood sugar levels.
These results raise an important concern regarding the prolonged use of these drugs by diabetes patients.
The study’s senior author, Dr. Per-Olof Berggren, professor at the Rolf Luft Research Centre for Diabetes and Endocrinology at Karolinska Institutet’s Department of Molecular Medicine and Surgery, said in a press release, “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. Our study also shows in general how to carry out in vivo (in living subjects) studies of the long-term effects of drugs on human insulin-producing cells, which should be extremely important to the drug industry.”