Association between integrase strand transfer inhibitor use with insulin resistance and incident diabetes mellitus in persons living with HIV: a systematic review and meta-analysis

Whether integrase strand transfer inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus (DM) than other antiretroviral therapies (ART) needs to be established.MEDLINE, Embase, Web of Science, and ClinicalTrials.gov registries were searched for studies published between 1 January 2000 and 15 June 2022. Eligible studies reported incident DM or mean changes in insulin resistance measured by Homeostatic Model for Insulin Resistance (HOMA-IR) in patients on INSTIs compared with other ARTs. We performed random-effects meta-analyses to obtain pooled relative risks (RRs) with 95% CIs.A total of 16 studies were pooled: 13 studies meta-analyzed for incident diabetes with a patient population of 72 404 and 3 for changes in HOMA-IR. INSTI therapy was associated with a lower risk of incident diabetes in 13 studies (RR 0.80, 95% CI 0.67 to 0.96, I-2=29%), of which 8 randomized controlled trials demonstrated a 22% reduced risk (RR 0.88, 95% CI 0.81 to 0.96, I-2=0%). INSTIs had a lower risk compared with non-nucleoside reverse transcriptase inhibitors (RR 0.75, 95% CI 0.63 to 0.89, I-2=0%) but similar to protease inhibitor-based therapy (RR 0.78, 95% CI 0.61 to 1.01, I-2=27%). The risk was lower in studies with longer follow-up (RR 0.70, 95% CI 0.53 to 0.94, I-2=24%) and among ART-naive patients (RR 0.78, 95% CI 0.65 to 0.94, I-2=3%) but increased in African populations (RR 2.99, 95% CI 2.53 to 3.54, I-2=0%).In conclusion, exposure to INSTIs was not associated with increased risk of DM, except in the African population. Stratified analyses suggested reduced risk among ART-naive patients and studies with longer follow-up.International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42021273040.

Automated summary

This meta-analysis found that there is no significant association between integrase strand transfer inhibitors (INSTIs) and an increased risk of type 2 diabetes mellitus (DM) compared to other antiretroviral therapies (ARTs), except in the African population. However, it is important to note that exposure to INSTIs may increase the risk of DM in African populations. Additionally, lower risk of DM was observed in studies involving ART-naive patients and longer follow-up periods.