Abstract: FR-OR091

Effect of the SGLT2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes and Stages 3b-4 CKD

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Wheeler, David C., University College London, London, LONDON, United Kingdom
  • Dekkers, Claire, University Medical Center Groningen, Groningen, Netherlands
  • Sjostrom, David, AstraZeneca LP, Molndal, Sweden
  • Stefansson, Bergur V., AstraZeneca, Molndal, Sweden
  • Cain, Valerie, Bogier Clinical and IT Solutions, Inc, Haddonfield, New Jersey, United States
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
Background

Dapagliflozin, an anti-diabetic drug targeting the sodium-glucose co-transporter 2, decreases HbA1c, body weight, blood pressure (BP), and albuminuria (UACR) in patients with type 2 diabetes. Although the glucose lowering capacity of dapagliflozin is diminished in patients with reduced kidney function, the effects of this drug on body weight, BP, and UACR as well as its safety have not been properly defined in patients with type 2 diabetes and stages 3b-4 chronic kidney disease (CKD).

Methods

In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined changes in HbA1c, body weight, BP, hematocrit, eGFR, and UACR over 24 weeks in patients with type 2 diabetes and an eGFR <45 ml/min/1.73m2 receiving placebo (n=70) or dapagliflozin 5 mg or 10 mg (n=151). Effects on UACR were determined in a subgroup of patients with baseline UACR ≥ 30 mg/g (n=137).

Results

Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10 mg were -0.02 (95% CI: -0.36, 0.33) and -0.03 (95% CI: -0.34, 0.28). Dapagliflozin 5 and 10 mg compared to placebo changed eGFR after 24 weeks by -1.5 (95% CI: -4.6, 1.5) and -2.6 (95% CI: -5.3, 0.2) and UACR by -48.3% (95% CI: -67.4, -17.8), and -32.7% (95% CI: -56.2, 3.5), respectively. Additionally, dapagliflozin at both 5 and 10 mg compared to placebo increased hematocrit and decreased body weight and BP. The overall frequency of adverse events was similar among treatment groups. Adverse events associated with renal function occurred more frequently in the dapagliflozin 10 mg group. These events included many asymptomatic increases in serum creatinine of which none qualified as a serious adverse event.

Conclusion

Dapagliflozin does not decrease HbA1c in patients with type 2 diabetes and stages 3b-4 CKD. However, the drug decreases UACR, BP, and body weight to a clinically meaningful extent without major side effects. These actions of dapagliflozin support a large outcomes trial in this population to confirm long-term safety and efficacy in reducing adverse clinical end points.

Funding

  • Commercial Support