DRI Study Shows Effects of Long-Term Drugs on Insulin-Producing Cells

An important study led by researchers at the Diabetes Research Institute (DRI) at the University of Miami’s Miller School of Medicine shows the effects of liraglutide, a popular GLP-1 analog, on the function of human pancreatic islets after long-term daily treatment in humanized mice.

The study, published online on February 11 in the journal Cell Metabolism, was led by DRI researchers Midhat H. Abdulreda, Ph.D., assistant professor, and Per-Olof Berggren, Ph.D., adjunct professor of surgery, in collaboration with Alejandro Caicedo, Ph.D., associate professor, and Rayner Rodriguez-Diaz, Ph.D., senior research associate, in the Department of Medicine.

As part of the lab research, humanized mice were generated by transplanting human pancreatic islets into the anterior chamber of the eye, which allowed long-term follow-up and revealed unexpected consequences after continuous daily treatment with liraglutide. The results showed that prolonged liraglutide treatment was associated with initial improvement in human islet function that was followed by an unexpected progressive deterioration over time.

The unanticipated findings raise concern about the potential impact of continuous multi-year use of the popular GLP-1 analogs in diabetic patients.

“These findings, albeit preliminary, are critical given the current lack of clinical information on the effects of these drugs after many years of continuous use in diabetic patients” said Abdulreda. “We were surprised by these findings, as we expected, based on what we know about these drugs, that liraglutide treatment will improve islet function.”

Researchers concluded that the findings are consistent with the notion that “excessive” activation of the already overworked insulin-producing beta cells under diabetic conditions during long-term treatment with incretin mimetics may lead to metabolic exhaustion of these cells and, ultimately, worsening in the control of blood sugar levels in diabetic patients.

“The findings of the paper are conceptually important to consider prior to prescribing long-term multi-year continuous usage of GLP-1 analogs for the treatment of diabetes,” said Berggren. “This study points to the uniqueness of the humanized mouse anterior chamber of the eye model that we have developed for drug screening.”

The study is expected to be published in print in the journal’s March edition.

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