Clinical, biological, metabolic, and immune changes associated with the use of sodium-glucose cotransporter 2 inhibitors in people living with HIV

Abstract

Introduction: Positive cardiovascular and renal outcomes associated with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) use are attributed to their anti-inflammatory properties. Persistent immune activation accounts for part of the elevated cardiovascular risk of people living with HIV (PWH), but SGLT2i impact on this population has been poorly described.

Methods: All PWH with a history of SGLT2i treatment from May 2020 to April 2023 receiving care at Pitié-Salpêtrière Hospital (Paris, France) and with available pre- and post-treatment blood samples were included. Clinical and biological data were extracted from medical records, metabolic and immune biomarkers from cryopreserved plasma samples.

Results: Most of the 20 patients with SGLT2i treatment were men (75 %), with a median [IQR] age of 59 years [55;68], receiving antiretroviral therapy for a median of 21.5 years [15.3;26.5]. Most had type 2 diabetes (95 %), chronic kidney disease (90 %), dyslipidemia (80 %), and hypertension (75 %). SGLT2i treatment was associated with a median weight loss of 3 kg, an increase in hematocrit, and decreased AST levels. LDL, HDL, oxLDL, and Lp-PLA2 levels were unaffected. SGLT2i was associated with inflammasome inhibition and with decreased circulating levels of IL-1β and IL-8. We also observed a decrease in cytokines associated with the recruitment and activation of monocytes-macrophages MCP-1, MIP-1α, MIP-1β, Eotaxin, RANTES, IL-8, and their positive feedback, IL-13/IL-4. Decreased IL-6, CRP, and sCD14 levels were not significant.

Conclusion: SGLT2i was associated with weight loss and a significant impact on innate immunity in PWH, with inhibition of inflammasome and monocyte-macrophage activation.

Keywords: Dapagliflozin; Empagliflozin; HIV; Metabolism; SGLT2.