Kidney Week

Abstract: TH-PO1141

The FAGOTTO Trial: Randomized Controlled Trial for Impact on Renal Hemodynamics of the SGLT2 Inhibitor Canagliflozin in Diabetic Kidney Disease

Session Information

• Late-Breaking Posters
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Nishibori, Nobuhiro, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Nobuhiro Nishibori,

• Kato, Sawako, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Sawako Kato,

• Saka, Yosuke, Kasugai Shimin Byoin, Kasugai, Japan

Yosuke Saka,

• Mizukoshi, Toshihiro, Kaikoukai, Nagoya, Japan

Toshihiro Mizukoshi,

• Naruse, Tomohiko, Kasugai Shimin Byoin, Kasugai, Japan

Tomohiko Naruse,

• Kasuga, Hirotake, Kaikoukai, Nagoya, Japan

Hirotake Kasuga,

• Miyata, Takashi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Takashi Miyata,

• Ando, Masahiko, Nagoya Daigaku Igakubu Fuzoku Byoin, Nagoya, Aichi, Japan

Masahiko Ando,

• Kuwatsuka, Yachiyo, Nagoya Daigaku Igakubu Fuzoku Byoin, Nagoya, Aichi, Japan

Yachiyo Kuwatsuka,

• Arima, Hiroshi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Hiroshi Arima,

• Maruyama, Shoichi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Shoichi Maruyama,

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have a potential to maintain renal function in the long-term despite of a dip on glomerular filtration rate (GFR) slope shortly after administration. We evaluated change of renal hemodynamics during GFR dip in patients (pts) with type 2 diabetic kidney disease (DKD) with moderate renal dysfunction [30 ≤ estimated GFR (eGFR) ≤ 60 mL/min/1.73 m²].

Methods

The FAGOTTO (jRCTs041200069) was a 12-week multicenter, open-label, randomized (1:1=canagliflozin : control), parallel-group trial. We directly measured GFR (mGFR) and effective renal plasma flow (eRPF) by the clearance of inulin and para-aminohippuric acid at baseline and 4 weeks after start of the trial. We also assessed glomerular filtration fraction (FF), renal blood flow (RBF) and renal vascular resistance (RVR). The primary endpoint was change in FF.

Results

A total 111 pts were allocated. Mean age was 71 yrs; 73% were male; mean GFR, albuminuria and HbA1c were 46.0 ml/min, 371 mg/gCr and 6.9 %, respectively. Canagliflozin significantly reduced mGFR by -4.9 ml/min (95% CI: -7.2 to -2.6, P =0.0008), eRPF by -18.5 ml/min (-33.7 to -3.3, P = 0.0093), and RBF by -25.6 ml/min (-52.3 to 1.06, P = 0.021) vs control, respectively. No changes were observed in FF and RVR between these two groups. Figure shows the direct values. eGFRs were estimated 54.3, 50.8 and 48.6 ml/min in pts treated with canagliflozin and 54.7, 54.7 and 52.0 in controls at baseline, 4 and 12 weeks in a linear mixed model, respectively. Canagliflozin reduced eGFR after 4-week treatment (P = 0.009) and also 12-week (P = 0.032) vs control using Tukey-Kramer to correct for multiplicity.

Conclusion

SGLT2 inhibition reduced GFR and RPF while remained the levels of FF and RVR in DKD pts with moderate renal dysfunction.

Funding

• Commercial Support – Mitsubishi Tanabe Pharma Corporation Co., Ltd.