Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial
Authors' conclusion
In this randomized clinical trial, among people with T2D and predominantly free of kidney disease at baseline, no significant differences in kidney outcomes were observed during 5 years of follow-up when a dipeptidyl peptidase 4 inhibitor, sulfonylurea, glucagonlike peptide 1 receptor agonist, or basal insulin was added to metformin for glycemic control.
Study context
- Population
- Adults with T2D <10 years, HbA1c 6.8%–8.5%, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m², on metformin; 36 US sites
- Participants
- 5,047 adults
- Comparison
- Insulin glargine vs glimepiride vs liraglutide vs sitagliptin, each added to metformin
- Primary endpoint
- Chronic eGFR slope (change in eGFR between year 1 and trial end) and composite kidney disease progression (albuminuria, dialysis, transplant, or death due to kidney disease)
- Follow-up
- Mean 5.0 years (range, 0-7.6 years)
Methodological detailsmulticentre, comparative effectiveness, intention-to-treat
- Multicentre
- Comparative effectiveness
- Intention-to-treat
Primary result
As reported in the abstract
Sitagliptin
−2.03
mean · 95% CI −2.20–-1.86 · mL/min/1.73 m² per year
Glimepiride
−1.92
mean · 95% CI −2.08–-1.75 · mL/min/1.73 m² per year
Liraglutide
−2.08
mean · 95% CI −2.26–-1.90 · mL/min/1.73 m² per year
Insulin glargine
−2.02
mean · 95% CI −2.19–-1.84 · mL/min/1.73 m² per year
P = 0.61
Secondary outcomes
Composite kidney disease progression (co-primary) · across 4 groups
P = 0.56
- Composite kidney disease progression (co-primary) — Share of composite attributable to albuminuria progression
- 98.4%
Secondary outcomes (incident eGFR <60, 40% eGFR decline, urine albumin-to-creatinine ratio (UACR) doubling, KDIGO stage progression)
- No significant differences by treatment assignment
Safety
- No adverse kidney events attributable to medication assignment
Original publication
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