Table 1 Summary of evidence on the role of SGLT2 inhibitors in PD
From: SGLT2 inhibitors in peritoneal dialysis: a promising frontier toward improved patient outcomes
Study | Subjects | SGLT2 inhibitors | Key findings |
|---|---|---|---|
Alhwiesh et al. [129] | 50 patients with T2DM on insulin, who were treated with APD | Dapagliflozin | Decrease in insulin requirement by 2.6 units, HbA1c by 1.6%, body weight by 2.6 kg, fasting blood glucose by 36.4 mg/dL, serum CRP by 2.0 mg/dL, serum ferritin by 261.3 µg/L, and mean systolic blood pressure by 14 mmHg; increase in urine volume by 253.2 mL/24 h, ultrafiltration volume by 229.9 mL. No effect on the status of the high-glucose transporter |
Lai et al. [130] | 4 patients treated with PD | Dapagliflozin | Increase in peritoneal ultrafiltration |
Zhou et al. [124] | Rat PD model | Empagliflozin | Reduction in glucose uptake and increase in ultrafiltration through the rat peritoneum. Inhibition of glucose uptake by human PMCs |
Martus et al. [126] | Rat PD model | Empagliflozin | Increased urinary glucose excretion and decreased plasma glucose levels after PD. No significant changes in sodium or water transport across the peritoneal membrane |
Martus et al. [127] | Rat PD model | Phlorizin | Increase in urinary glucose excretion, decrease in plasma glucose, and increase in plasma creatinine after PD. Increase in glucose concentration in the dialysate after 60 min and no difference after 120 min |
Balzer et al. [123] | Mouse model of chronic peritoneal exposure to high-glucose dialysate and human peritoneal samples in vitro | Dapagliflozin | Reduced PDE–TGF-β concentrations, peritoneal thickening and fibrosis, and microvessel density, leading to improved ultrafiltration. In vitro, dapagliflozin reduced the release of MCP-1. No effect on the status of the high-glucose transporter |
Shi et al. [98] | Rat PD model and human PMCs in vitro | Empagliflozin | Improvement of peritoneal function, reduction of the thickness of the peritoneum and improvement of collagen accumulation. Inhibition of high glucose-induced EMT and oxidative stress by activating the Nrf2/HO-1 signaling pathway |
Shentu et al. [125] | Mouse PD model and human PMCs in vitro | Empagliflozin | Protective effect on high glucose-induced peritoneal fibrosis by suppressing TGF-β/Smad signaling: reducing levels of inflammatory cytokines (TNF-α, IL-1β, IL-6), TGF-β1, α-smooth muscle actin, collagen I and p-Smad3 accumulation in PMCs |
Wang et al. [128] | Rat PD model and human PMCs in vitro | Canagliflozin | Improvement of peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-β/p-Smad3 signaling pathway |