Impact of SGLT2 Inhibitors on Kidney Function Among People With HIV: A US Prospective Multisite Study

Area of Science:

• Nephrology
• Infectious Diseases (HIV/AIDS)
• Pharmacology

Background:

• Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for kidney protection but can cause an early estimated glomerular filtration rate (eGFR) decline, termed 'eGFR dip'.
• This phenomenon is understudied in people with HIV (PWH), who have an elevated risk of kidney disease.

Purpose of the Study:

• To investigate the incidence and magnitude of early eGFR decline in PWH initiating SGLT2i compared to other antihyperglycemic agents.
• To analyze the longer-term eGFR trends over 24 months in PWH using SGLT2i.

Main Methods:

• A 1:1 propensity score-matched cohort study was conducted using data from 9 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites.
• New SGLT2i users were compared with new users of other antihyperglycemic classes.
• Adjusted hazard ratios (aHRs) for eGFR decline (≥10% and ≥30%) and multivariable linear mixed models for eGFR change were used. Longer-term trends were visualized using locally weighted scatterplot smoothing (LOWESS) curves.

Main Results:

• Among 295 matched pairs of PWH, SGLT2i users showed a higher incidence of ≥10% eGFR decline (58.2% vs. 37.4%; aHR: 1.79) and ≥30% eGFR decline (17.3% vs. 9.8%; aHR: 1.69) over 6 months.
• The adjusted mean eGFR change at 6 months was -2.62 mL/min/1.73m² for SGLT2i users versus 0.05 mL/min/1.73m² for other classes.
• Long-term analysis revealed an initial eGFR dip after SGLT2i initiation, followed by stabilization and a slower decline compared to other antihyperglycemic classes.

Conclusions:

• Acute eGFR dips are more frequent in PWH initiating SGLT2i compared to other antihyperglycemic agents.
• However, these declines are small, transient, and consistent with findings in the general population.
• Further research is warranted to fully understand the long-term renal effects of SGLT2i in PWH.