Among patients diagnosed with HIV-1 or hepatitis B, the adjusted risk of incident type 2 diabetes was 33% lower among those who had been exposed to nucleoside reverse-transcriptase inhibitor (NRTI) drugs compared with those not exposed, suggesting that NRTIs have the potential to be repurposed for diabetes prevention in the future, according to a study published in Nature Communications.
After examining patient data from the Veterans Health Administration (VHA) over a 17-year period, researchers concluded that NRTIs are associated with a reduced risk of developing type 2 diabetes after adjusting for sociodemographic factors and comorbidities. To confirm this finding among more diverse populations, researchers examined patient data from 4 additional insurance databases: Truven, PearlDriver, Medicare, and Clinformatics.
In the VHA database, a total of 79,744 patients had a confirmed diagnoses of HIV or hepatitis B and did not have a prior type 2 diabetes diagnosis; 12,311 of these patients eventually developed type 2 diabetes. NRTI users had a 34% reduced risk of developing type 2 diabetes.
In the Truven database, 1630 of 23,634 HIV-positive or hepatitis B-positive patients developed incident type 2 diabetes; NRTI users had a 39% reduced risk of developing diabetes compared to non-NRTI users. Similarly, 1068 of 16,045 eligible patients in the PearlDriver database developed type 2 diabetes; NRTI users had a 26% reduced risk. A total of 3097 Medicare patients were eligible; 707 of these patients developed type 2 diabetes, and NRTI users had a 17% reduced risk. Researchers identified 6341 eligible patients in the Clinformatics database, 1067 of whom developed type 2 diabetes. NRTI users in this group had a 27% reduced hazard of developing type 2 diabetes.
At 1, 2, 5, and 10 years of follow up, NRTI users maintained a reduced hazard of developing type 2 diabetes. In the VHA cohort, follow-up durations and mortality rates were comparable between NRTI users and non-users; researchers concluded that differences in mortality rates were not responsible for the observed risk reduction for type 2 diabetes among NRTI users.
Among patients in the VHA cohort who were hepatitis B-positive and HIV-negative, NRTI use was associated with a 28% reduced risk for developing type 2 diabetes. For HIV-positive and hepatitis B-negative patients, researchers observed a 38% reduced risk for type 2 diabetes in the veterans cohort.
With each additional year of using NRTIs, patients diagnosed with HIV-1 or hepatitis B in all 5 cohorts had a 3% to 8% reduced hazard of developing type 2 diabetes. Researchers could not establish a consistent association between other drug classes aside from NRTIs that are used to treat HIV or hepatitis B and incident development of type 2 diabetes.
Researchers then studied insulin resistance-induced human cells to observe the effects NRTIs have on non-HIV-positive or hepatitis B-positive patients, and concluded that NRTI drugs such as lamivudine, azidothymidine, and stavudine were effective in improving insulin resistance.
“We find that NRTI exposure is associated with reduced development of type 2 diabetes in people and that lamivudine inhibits inflammasome activation and improves insulin sensitivity in experimental systems,” concluded the study authors.”
Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Ambati J, Magagnoli J, Leung H, et al. Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development. Nat Commun. 2020;11(1):4737.