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2025 ISPE Annual Meeting Main banner

Safety Outcomes / Other

5E-05 - Acute eGFR Dip with SGLT2 Inhibitors vs. Other Antihyperglycemic Medications Among People with HIV

Tuesday, August 26, 2025
9:30 AM - 9:45 AM ET
Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in the general population but can cause an acute dip in estimated glomerular filtration rate (eGFR), raising safety concerns, particularly in people with HIV (PWH) who may be more vulnerable to renal complications.

Objectives: To assess the risk of acute eGFR decline with SGLT2i vs other antihyperglycemic classes, and to explore longer-term eGFR trends over 24 months.

Methods: We conducted an observational study using a new-user, active-comparator design with data from 9 sites within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. PWH initiating SGLT2i or other antihyperglycemic agents (glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i), or sulfonylureas) between 2013 and 2023 were included if they had ≥2 eGFR measurements: 1 at baseline and 1 within 6 months of medication initiation. Outcomes were time to ≥10% and ≥30% eGFR decline within 6 months of medication initiation. We used 1:1 propensity score matching to balance covariates between new users of SGLT2i and other antihyperglycemic medications. Propensity scores were estimated using logistic regression model including baseline age, sex, race/ethnicity, eGFR, comorbidities, and comedications as covariates. Cox proportional hazards models were used to compare risks between SGLT2i and other antihyperglycemic classes following an intention-to-treat analysis. Additionally, longer-term eGFR trends over 24 months were visualized using locally weighted scatterplot smoothing (LOWESS) curves.

Results: Among 1554 (299 initiating SGLT2i and 1255 initiating other antihyperglycemic classes), 295 SGLT2i new users were matched to 295 new users of other antihyperglycemic medications. After matching, baseline characteristics were similar between groups, including age (56 vs 57 years), sex (80% vs 83% male), and eGFR (71 vs 71 mL/min/1.73 m²). At 6 months, SGLT2i users had a higher incidence of ≥10% (58.2% vs. 37.4%; aHR 1.79, 95% CI: 1.40–2.28) and ≥30% (17.3% vs. 9.8%; aHR 1.69, 95% CI: 1.05–2.73) eGFR declines compared to users of other antihyperglycemic classes. Long-term eGFR trends revealed an initial decline following SGLT2i initiation, followed by stabilization and a slower subsequent decline compared to other classes.

Conclusions: Acute eGFR dips were more common in PWH initiating SGLT2i, but declines were modest, transient, and consistent with patterns seen in the general population. Further research is needed to assess long-term renal effects of SGLT2i in PWH.