META-INSTI: metabolic adverse events following integrase strand transfer inhibitor administration in spontaneous adverse event reports

Abstract

Background: Unexpected metabolic effects of integrase inhibitors (INSTIs) have been reported in the literature. The FDA Adverse Event Reporting System (FAERS) is a publicly available database that captures spontaneously reported adverse events. Analysis of these data allows for the determination of whether rare or unknown events represent a cause for concern. The objective of this study was to evaluate the relationship between INSTIs and metabolic adverse events using the FAERS database. Method(s): FAERS data were queried from quarter 4 2007 through quarter 4 2019 and limited to adults. The Standardized MedDRA Query (SMQ) for hyperglycemia/ new onset diabetes mellitus (H/DM) was used to identify metabolic adverse events of interest. Weight gain was defined as increased weight or increased BMI and was analyzed as a separate event. Reporting odds ratios (ROR) and 95% Confidence Intervals (CIs) were calculated for the INSTI class and for individual agents. Result(s): Over 10.1 million FAERS reports were identified. H/DM was noted in 732,591 reports (7.2%); 109,566 (1.1%) reported weight gain. Consumers (49%) and physicians (23%) were the most common reporters. The most frequent countries of occurrence were the US, Great Britain, and Japan. The mean (SD) age was 57 (17) years with 63% females. Any INSTI was mentioned as a primary and/or secondary suspect agent in 18,400 (0.18%) reports (bictegravir: 1,414 [0.01%]; dolutegravir: 7,840 [0.08%]; elvitegravir: 4,034 [0.04%]; raltegravir: 5,551 [0.05%]). RORs (95% CI) for H/DM and weight gain for any INSTI were 1.20 (1.15, 1.27) and 2.16 (1.96, 2.38). For individual agents, RORs (95% CI) for H/DM and weight gain were bictegravir: 1.23 (1.10, 1.37) and 6.82 (5.50, 8.41); dolutegravir: 1.28 (1.19, 1.39) and 1.86 (1.58, 2.18); elvitegravir: 0.76 (0.56, 1.02) and 1.63 (1.37, 1.92); raltegravir: 1.00 (0.90, 1.11) and 3.29 (2.77, 3.91). H/DM was noted in 159 bictegravir and 712 dolutegravir reports. Conclusion(s): Overall, H/DM was associated with bictegravir and dolutegravir; weight gain was associated with all INSTIs. Clinicians should be aware of the potential relationship with INSTIs and concerning metabolic effects and institute appropriate monitoring. Future clinical studies to evaluate these findings are warranted.