Integrase strand transfer inhibitor–related changes in body mass index and risk of diabetes: A prospective study from the RESPOND cohort consortium. Clinical Infectious Diseases
Integrase strand transfer inhibitors (INSTIs) are widely used in HIV treatment due to their strong efficacy and tolerability. However, emerging evidence suggests a link between INSTI use, weight gain, and increased risk of type 2 diabetes (DM).
In this prospective cohort study, Rupasinghe et al. analyzed data from over 20’000 people with HIV across 19 cohorts in Europe and Australia. Participants were followed for a median of 4.8 years. The study investigated how INSTI use and changes in body mass index (BMI) influenced the risk of developing DM.
Key findings:
- 785 participants developed incident DM, with a crude incidence rate of 0.73/100 person-years.
- Current INSTI use was associated with a 48% higher risk of developing DM compared to non-INSTI use, even after adjusting for BMI and other risk factors.
- Higher BMI remained a strong independent predictor of diabetes across all treatment groups.
- The increased DM risk was most evident among individuals using dolutegravir or raltegravir.
- No significant difference in diabetes risk was found between users of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF).
These findings suggest that INSTIs may increase diabetes risk partly through weight gain and possibly through other mechanisms. The authors recommend continued monitoring of weight and metabolic health in people with HIV, particularly when initiating or switching to INSTI-based regimens.