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Abstract: TH-PO973

Comparative Effectiveness of Glucose-Lowering Medications on Kidney Outcomes in the Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness (GRADE) Randomized Clinical Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Wexler, Deborah J., Massachusetts General Hospital, Boston, Massachusetts, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
  • Ghosh, Alokananda, The George Washington University Milken Institute of Public Health, Rockville, Maryland, United States
  • Mudaliar, Sunder, VA San Diego Healthcare System, San Diego, California, United States
  • Younes, Naji, The George Washington University Milken Institute of Public Health, Rockville, Maryland, United States
  • Bebu, Ionut, The George Washington University Milken Institute of Public Health, Rockville, Maryland, United States
  • McGill, Janet B., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Tamborlane, William V., Yale School of Medicine, New Haven, Connecticut, United States
  • Tan, Menghee, University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • The GRADE Research Group

Here we report kidney outcomes in the GRADE Study, which evaluated the comparative effectiveness of sitagliptin, glimepiride, liraglutide, or insulin glargine added to metformin for glucose control in individuals with type 2 diabetes (T2D); basal or prandial insulin was added to maintain glycemic control if the HbA1c exceeded 7.5% on the assigned combination.


Co-primary outcomes: slope of eGFR, measured annually, between year 1 and end of follow up; and a composite of kidney disease progression (progression to moderately or severely elevated albuminuria, kidney transplant, dialysis, or death). Secondary outcomes were incident eGFR <60 mL/min/1.73m2, 40% decline in eGFR to <60 mL/min/1.73m2, doubling of urine albumin-creatinine ratio to ≥30 mg/g, and KDIGO stage progression.


GRADE enrolled 5,047 participants with baseline mean (SD) age 57.2 years (10.0), HbA1c 7.5% (0.5), diabetes duration 4.2 (2.8) years, BMI 34.3 (6.8) kg/m2, blood pressure 128/77 mmHg (15/10), eGFR 94.9 (16.8) mL/min/1.73m2, and median urinary albumin-to-creatinine ratio (UACR) 6.4 (IQR 3.1, 16.9) mg/g; 58% were treated with ACE inhibitor or angiotensin receptor blocker. Mean follow-up was 5.0 (range 0-7.6) years. Mean (95% CI) eGFR slope was -2.03 (-2.20, -1.86), -1.92 (-2.08, -1.75), -2.08 (-2.26, -1.90), and -2.02 (-2.19, -1.84), mL/min/1.73m2/year among participants assigned to sitagliptin, glimepiride, liraglutide, and insulin glargine, respectively (p=0.61). The composite kidney disease progression outcome occurred among 135 (10.6%), 155 (12.4%), 152 (12.0%), and 150 (11.9%), participants, respectively (p=0.56). Moderately (83%) and severely (15.8%) elevated albuminuria accounted for the majority of kidney disease progression. There were no differences by treatment arm in secondary outcomes.


Among people with T2D and little or no evidence of prevalent kidney disease, we observed no difference in kidney outcomes over 5 years when a DPP-4 inhibitor, sulfonylurea, GLP-1 receptor agonist, or basal insulin was added to metformin.


  • NIDDK Support