UVA Study Suggests NRTIs Could Reduce Risk of Developing Type 2 Diabetes

Jayakrishna Ambati, MD

A new study suggests use of therapies in a class known for treating hepatitis B and human immunodeficiency virus (HIV) could be useful in the management of a different disease.

Results of the study, which pooled data from 5 major databases, suggest use of nucleoside reverse-transcriptase inhibitors (NRTIs) was associated with a 33% decrease in risk of developing type 2 diabetes.

“The large scale of these clinical data and the size of the protective effect provide evidence that inflammasome inhibition in humans is beneficial,” said study investigator Jayakrishna Ambati, MD, professor at the University of Virginia School of Medicine, in a statement. “We are hopeful that prospective clinical trials will establish that inflammasome inhibitors known as Kamuvudines, which are less-toxic derivatives of NRTIs, will be effective not only in diabetes but also in macular degeneration and Alzheimer’s disease.”

While previously published data have suggested potential mechanistic benefits of NRTIs on the development of type 2 diabetes, Ambati and a team of UVA clinicians sought to determine whether this would translate into a clinical benefit in a real-world setting. With this in mind, they designed the current study as an analysis of real-world data related to use of NRTIs from multiple databases.

Specific databases included in the investigators’ analyses included Veterans Health Administration database, the Truven database, the PearlDiver database, the Medicare database, and the Clinformatics database. Of note, the study was originally designed to examine associations between exposure to NRTIs and development of type 2 diabetes in the Veterans Health Administration database and then assess the validity of these findings through analysis of the other 4 databases. In total, a cohort of 128,861 patients was obtained from the 5 databases.

In the main analysis, investigators identified a total of 79,744 patients with confirmed diagnoses of HIV or hepatitis B without a prior diagnosis of type 2 diabetes. During the follow-up period, 12,311 patients developed type 2 diabetes and results of the analysis suggested users of NRTIs were at a 34% lower risk of developing type 2 diabetes than their counterparts not receiving NRTIs (HR, 0.665; 95% CI, 0.625-0.708; P <.0001).

From the Truven database, investigators identified a cohort of 23,634 patients. Of these, 1630 went on to develop type 2 diabetes. In adjusted models, users of NRTIs were at a 39% lower risk of developing type 2 diabetes (HR, 0.614; 95% CI, 0.524-0.718; P <.0001). From the PearlDiver database, investigators identified a cohort of 16,045 patients. Of these, 1068 went to on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 26% lower risk of developing type 2 diabetes.

In the Medicare database, investigators identified a cohort of 3097 patients. Of these, 707 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 17% lower risk of develop type 2 diabetes (HR, 0.828; 95% CI, 0.646-1.062; P=.137). In the Clinformatics datable, investigators identified a cohort of 6341 patients. Of these, 1067 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 27% lower risk of developing type 2 diabetes (HR, 0.727; 95% CI, 0.572-0.924; P=.009).

In a pooled analysis including all 128,861 patients from the 5 databases, investigators found the adjusted risk of diabetes was 33% lower among patients with NRTI exposure (HR, 0.673; 95% CI, 0.638-0.710; P <.0001; 95% Prediction Interval, 0.618-0.734).

This study, “Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development,” was published in Nature Communications.