Pharmacovigilance study of INSTIs associated with weight gain and glucose/lipid metabolism adverse events based on the FDA adverse event reporting system

Abstract

Objective: Integrase strand transfer inhibitors (INSTIs) are widely used in antiretroviral therapy (ART) for people with HIV due to their efficacy and tolerability. However, concerns about weight gain and metabolic disturbances have emerged. This study aimed to evaluate the association between INSTIs and metabolic adverse events (AEs), including weight gain and glucose/lipid disorders.

Design: The US Food and Drug Administration Adverse Event Reporting System (FAERS) reports from the first quarter (Q1) of 2004 through Q1 2025 were analysed for AEs associated with bictegravir (BIC), dolutegravir (DTG), elvitegravir (EVG) and raltegravir (RAL), focusing on weight gain and glucose/lipid metabolism disorders. Kaplan-Meier curves and Weibull shape parameter tests were used to analyse the cumulative incidence and time to onset of AEs.

Results: All four INSTIs were associated with safety signals for weight gain and glucose/lipid metabolism disorders. BIC had the highest reporting odds ratio (ROR) for weight gain (ROR: 7.70, 95% CI: 7.00-8.47), while DTG had the highest for glucose/lipid disorders (1.81, 95% CI: 1.66-1.97). Younger age and female sex were linked to BIC-related weight gain; older age was a risk factor for DTG-, EVG- and RAL-related glucose/lipid AEs. DTG-associated events occurred earlier than those with other agents.

Conclusion: This study identified metabolic AEs associated with INSTIs, with agent-specific differences in risk and timing, highlighting the need for regular monitoring and individualized management during INSTI-based ART.

Keywords: FAERS; HIV; INSTIs; glucose and lipid metabolism disorders; weight gain.