From the Journals

HIV drugs prevent type 2 diabetes, may be path to new therapy


 

A class of drugs long used to treat HIV and hepatitis B viral infections appears to prevent the development of diabetes in a substantial proportion of patients who take these agents, an analysis of multiple databases has shown.

“Nucleoside reverse transcriptase inhibitors [NRTIs], drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation,” Jayakrishna Ambati, MD, University of Virginia, Charlottesville, and colleagues wrote in Nature Communications.

“[We showed that] the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure. ... These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes,” they wrote.

The researchers made a small chemical modification to NRTIs that led to their developing a new class of drugs, which they have termed “kamuvudines.” Kamuvudines are nontoxic derivatives of NRTIs, Dr. Ambati said in an interview.

“People take NRTIs because they need to live with HIV, but giving them to the general population is not a great idea because of the toxicities associated with long-term NRTI use. So our focus is not to go forward specifically with NRTIs but rather with these new molecules that are far less toxic, and that is how we envision a clinical trial going forward,” Dr. Ambati noted.

Researchers screened five databases of >100,000 patients

Dr. Ambati and colleagues analyzed information from five databases in which patients who had been exposed to an NRTI but who had not previously been diagnosed with type 2 diabetes were assessed for the subsequent development of diabetes over varying time intervals. In one, the Veterans Health Administration database – from the largest integrated health care system in the United States – the analysis spanned a period of 17 years.

Of 79,744 patients with a confirmed diagnosis of HIV or hepatitis B in the Veterans Health Administration database, the risk for type 2 diabetes was reduced by 34% among NRTI users, compared with nonusers after adjusting for potential confounders (P < .0001).

The reduction in diabetes risk was similar among HIV-positive and hepatitis B–positive patients.

These results were reaffirmed by further analyses of four other databases, the investigators reported. One of these, the employer-based health insurance Truven database, had data on 23,634 patients who had been diagnosed with HIV or hepatitis B. After adjusting for potential confounders, NRTI users had a 39% lower risk of developing type 2 diabetes, compared with nonusers (P < .0001).

The risk of developing type 2 diabetes was somewhat lower among NRTI users in the Pearl Diver database, which includes predominantly private health insurance claims. Of 16,045 patients diagnosed with HIV or hepatitis B included in this database, the risk for type 2 diabetes was 26% lower among NRTI users, compared with nonusers (P = .004).

A similar magnitude of risk reduction was seen in the analysis of the Clinformatics dataset. Among 6,341 users of NRTIs, the risk for type 2 diabetes was 27% lower than it was for nonusers (P = .009).

The least reduction in diabetes risk was in the Medicare database, in which only 3,097 patients had been diagnosed with either HIV or hepatitis B. Among these patients, the risk for diabetes was 17% lower among NRTI users than it was for nonusers (P = .137).

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