AbstractThe aim of this study was to investigate whether the use of nucleoside reverse transcriptase inhibitors (NRTIs) impacts the incidence of prediabetes or type 2 diabetes mellitus (T2DM) or the progression from prediabetes to T2DM in people living with HIV (PLWH). We conducted a retrospective cohort study using the US Veterans Health Administration database among adult patients with an HIV diagnosis from the year 2000 until 2021 to determine the incidence of prediabetes and further progression to T2DM among NRTI exposed and unexposed patients. A multistate model was used to evaluate progression from normoglycemia to prediabetes and then to T2DM, and covariate adjustment with the Cox proportional hazards model was used to estimate the hazard ratios (HRs). Among 32,240 veterans diagnosed with HIV, prediabetes and T2DM were observed among 20.2% and 20.7% of patients, respectively. Among those diagnosed with prediabetes, 31.8% progressed to T2DM. Patients exposed to NRTIs at any time (86.6%), had a reduced risk of prediabetes [HR: 0.50 (95% confidence interval, CI: 0.47–0.53)] and among prediabetics, a lower risk of progression to T2DM [HR: 0.73 (95% CI: 0.63–0.85)] when compared to patients who never used NRTIs. In summary, NRTIs may reduce the risk of developing prediabetes and the progression from prediabetes to T2DM in PLWH.