Introduction and Objective: Treatment with SGLT-2i reduces the risk of both cardiovascular and renal outcomes in type 2 diabetes (T2D). Recent findings indicate that in obese individuals, the kidney exhibits lower 18Fluorodeoxyglucose ([18F]-FDG) uptake rates compared to lean individuals, possibly due to insulin resistance. This study aims to evaluate changes in renal [18F]-FDG uptake in T2D patients following short-term treatment with dapagliflozin and to assess the long-term effects on kidney function after a four-year follow-up.Methods: In our DAPAHeart Trial, a single-center, four-week, prospective, double-blind, controlled study, we enrolled T2D patients with stable coronary artery disease and preserved glomerular filtration rates (eGFR >60 ml/min/1.73m²). Participants were randomly assigned in a 1:1 ratio to receive either dapagliflozin (10 mg daily) or a placebo. PET scans using [18F]-FDG were performed during a hyperinsulinemic-euglycemic clamp (HEC) to measure regional FDG uptake before and after the four-week treatment with SGLT-2i.Results: After the four-week treatment, the SGLT-2i group showed a significant reduction in renal standardized uptake value (SUV) expressed as peak activity concentrations (SUVpeak; p=0.045) compared to the placebo group, with trends toward reductions in SUVmax and SUVmean. Additionally, long-term follow-up data revealed that four years of dapagliflozin treatment was associated with stable eGFR (pre-treatment: 81.4 ± 6.4 ml/min; post-treatment: 76.2 ± 6 ml/min; p=0.4).Conclusion: Short-term treatment with dapagliflozin is associated with a reduction in renal SUVpeak, indicating decreased glucose uptake during an insulin-stimulated state (insulin clamp). While the causes of this reduction require further investigation, it is suggested that SGLT-2 inhibition decreases tubular energy requirements and glucose uptake, contributing to kidney function preservation, as confirmed by the four-year follow-up.
S. Gugliandolo: None. C. Morciano: None. G. Sorice: None. L. Leccisotti: None. U. Capece: None. A. Guarneri: None. T. Mezza: None. G. Di Giuseppe: None. G. Ciccarelli: None. L. Soldovieri: None. M. Brunetti: None. A. Avolio: None. A. Splendore: None. P. Iozzo: None. A. Giaccari: Board Member; Novo Nordisk A/S. Speaker’s Bureau; AstraZeneca, Sanofi. Advisory Panel; Sanofi. Speaker’s Bureau; Guidotti. F. Cinti: None.
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