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Abstract: FR-OR20

Metformin Improves Vascular Function in CKD Patients with Metabolic Syndrome

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Ramos, Everly, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Sahinoz, Melis, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Pena, Carlos O., Universidad Central de Venezuela, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of
  • Akwo, Elvis A., Tennesse Valley Healthcare System, Nashville, Tennessee, United States
  • Roumie, Christianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Yu, Zhihong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Cardiovascular (CV) risk is increased in CKD. Insulin resistance (IR), highly prevalent in CKD patients, contributes to endothelial dysfunction and arterial stiffness, leading to poor CV outcomes. It remains unknown if insulin sensitization with metformin improves CV risk, in patients with CKD Stage 3-4 and metabolic syndrome (MS).

Methods

In a double-blinded randomized trial (NCT02252081), 50 patients with CKD Stage 3, and MS and/or pre-diabetes, received either metformin or placebo for 16 weeks. Dosing was initiated at 500 mg and up-titrated over 7-14 days based on GI tolerance up to 1500 mg/day in CKD3a and 1000 mg/day in CKD 3b. Co-therapies for optimal CV risk reduction were continued. The co-primary outcomes included change in brachial artery flow-mediated dilation (FMD), aortic pulse-wave velocity (aPWV), and carotid intima-media thickness (CIMT) in common (CCA) and internal (ICA) carotid arteries, at 16 weeks. Lactic acid was obtained throughout the study for safety.

Results

Participants were 65 ± 10 years old and 80% were men. Mean [SD]: BMI 31.4 ± 5.1 kg/m2; SBP 130.5 ± 16 mmHg; DBP 74 ± 9 mmHg; HDL 46.4 ± 15 mg/dl; fasting glucose (FG) 92.3 ± 10.3 mg/dl; HbA1c 5.7 ± 0.24%; HOMA-IR 2.4±1.5, and eGFR was 50 ± 7 ml/min/1.73 m2. There were 8 patients (16%) in CKD Stage 3b, 3 in the metformin and 5 in the placebo group. Compared with placebo, metformin improved FMDBA (baseline: 6.24% ± 4.5% [mean±SD], 16 weeks: 12.06% ± 8.4% [mean±SD] with metformin and baseline: 6.12% ± 3.34% [mean±SD], 16 weeks: 7.6% ± 4.6% [mean±SD] with placebo, P=0.03 [Fig 1]), without changing aPWV (P=0.84) or CIMT: R CAA (P=0.10) L CCA (P=0.96) R ICA (P=0.74) L ICA(P=0.44).

Conclusion

Treatment with metformin improved FMDBA but not aPWV or CIMT in patients with CKD and IR. Studies of larger sample size and longer duration are required to further evaluate the effects on cardiovascular outcomes.

Funding

  • Veterans Affairs Support