Effects of bardoxolone methyl on body weight, waist circumference and glycemic control in obese patients with type 2 diabetes mellitus and stage 4 chronic kidney disease

J Diabetes Complications. 2018 Dec;32(12):1113-1117. doi: 10.1016/j.jdiacomp.2018.09.005. Epub 2018 Sep 13.

Abstract

Aims: Obesity is associated with progression of chronic kidney disease (CKD). Treatment with bardoxolone methyl in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate (eGFR) with concurrent reductions in body weight. We performed post-hoc analyses to further characterize reductions in body weight with bardoxolone methyl.

Methods: Eligible patients with type 2 diabetes (T2DM) and CKD stage 4 (eGFR 15 to <30 mL/min/1.73 m2) were randomized 1:1 to receive once-daily oral dose of bardoxolone methyl (20 mg) or placebo.

Results: BEACON enrolled 2185 patients. Patients randomized to bardoxolone methyl experienced significant reductions in body weight from baseline relative to patients randomized to placebo (-5.7 kg; 95% CI: -6.0 to -5.3 kg; p < 0.001). In patients randomized to bardoxolone methyl, rate and magnitude of body weight loss were proportional to baseline BMI. Bardoxolone methyl resulted in significant reductions in waist circumference and improved glycemic control.

Conclusions: Bardoxolone methyl resulted in significant weight loss in a generally obese patient population with T2DM and stage 4 CKD, with the magnitude and rate dependent on baseline BMI.

Keywords: Bardoxolone methyl; Chronic kidney disease; HbA(1c); Metabolic effects; Obesity; Randomized clinical trial.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Body Weight / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / pathology
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / complications
  • Obesity / drug therapy*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / therapeutic use
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / pathology
  • Waist Circumference / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Oleanolic Acid
  • bardoxolone methyl