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.