Background This study explores the relationship between different ART therapy based on NRTIs, and inflammatory markers, along with fasting blood glucose levels in treatment-naïve people living with HIV (PLWH). Methods We retrospectively analyzed the variations in fasting blood glucose and inflammatory markers and their relationship with different ART regimens in 497 treatment-naïve PLWH at the ART clinic of Zhongnan Hospital of Wuhan University from June 2018 to March 2022. Results From baseline to 24 months, fasting blood glucose, systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV) and lymphocyte-to-monocyte ratio (LMR) in PLWH receiving ART increased, while neutrophillymphocyte ratio (NLR) decreased ( p < .05). In the NNRTIs group, fasting blood glucose, SII, PIV and LMR were higher than before ( p < .05). In the INSTIs group, fasting blood glucose and LMR increased ( p < .05), while NLR was lower ( p < .05). Compared to the INSTIs, fasting blood glucose in the NNRTIs group was higher at 12 and 24 months ( p < .05). At 24 months, both NLR and SII were higher in the NNRTIs group than in the INSTIs group ( p < .05). Conclusions Despite the virus suppression, fasting blood glucose and certain inflammatory markers in PLWH can gradually increase. Compared to NNRTIs, the INSTIs regimen was associated with favorable alterations in the levels of glucose and inflammatory markers.