Doupe, Malcolm Bray

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are nephroprotective but are associated with early eGFR decline, also termed “eGFR dip.” Despite elevated risk of kidney disease, this phenomenon is understudied among people with HIV (PWH). Methods: In a 1:1 propensity score–matched cohort study using data from 9 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites, we compared new SGLT2i users with new users of other antihyperglycemic classes. We estimated adjusted hazard ratios (aHRs) for time to ≥10% and ≥30% eGFR decline using multivariable Cox proportional hazards models and analyzed eGFR change using multivariable linear mixed models. In addition, longer-term eGFR trends over 24 months were visualized using locally weighted scatterplot smoothing (LOWESS) curves. Results: Among 1554 eligible PWH, we obtained 295 matched pairs. Over 6 months, eGFR decline incidence of ≥10% and ≥30% was higher among users of SGLT2i versus other antihyperglycemic classes (58.2% vs. 37.4%; aHR: 1.79; 95% CI: 1.40%–2.28%; and 17.3% vs. 9.8%; aHR: 1.69; 95% CI: 1.05–2.73; respectively). The adjusted mean eGFR change at 6 months was −2.62 mL/min/1.73 m 2 for SGLT2i versus 0.05 mL/min/1.73 m 2 for other classes. Long-term eGFR trends revealed an expected initial decline after SGLT2i initiation, followed by stabilization and a slower subsequent decline compared with other classes. Conclusions: Acute eGFR dips were more common among PWH initiating SGLT2i relative to other antihyperglycemic classes, although overall declines were small, transient, and consistent with the general population. Further research is needed to explore the long-term effects of SGLT2i in PWH.