No differences found in effects of secondary diabetes drugs on kidney outcomes

There were no significant differences in kidney outcomes between drug classes added to metformin in a recent study of people with type 2 diabetes who were predominantly free of kidney disease at baseline.

Researchers conducted a randomized trial in 5,047 patients with type 2 diabetes who had been treated with metformin for less than 10 years, had an HbA1c level between 6.8% and 8.5%, and had an estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m². They were randomly assigned to receive a sulfonylurea, a dipeptidyl peptidase-4 (DPP-4) inhibitor, a glucagon-like peptide-1 (GLP-1) receptor agonist, or basal insulin. Metformin and the secondary drugs were continued unless the HbA1c level rose above 7.5%, after which insulin was added to maintain glycemic control. Patients were enrolled between July 2013 and August 2017 and followed for a mean of 5.0 years (range, 0 to 7.6 years). Results were published by JAMA Internal Medicine on May 22.

All groups had good glycemic and blood pressure management, and there were no significant differences between groups in progression of albuminuria, dialysis, kidney transplant, or death during five years of follow-up. Mean chronic eGFR slope was similar among the drugs at −2.03 (95% CI, −2.20 to −1.86) mL/min/1.73 m² per year for sitagliptin, −1.92 (95% CI, −2.08 to −1.75) mL/min/1.73 m² per year for glimepiride, −2.08 (95% CI, −2.26 to −1.90) mL/min/1.73 m² per year for liraglutide, and −2.02 (95% CI, −2.19 to −1.84) mL/min/1.73 m² per year for insulin glargine (P=0.61). On the mean composite outcome of kidney disease progression (albuminuria, dialysis, transplant, or death due to kidney disease) outcomes were also similar at 10.6% with sitagliptin, 12.4% with glimepiride, 12.0% with liraglutide, and 11.9% with insulin glargine (P=0.56). Most of the composite outcome was attributable to albuminuria progression (98.4%). No adverse kidney events were attributable to medication assignment.

“These results suggest that neither DPP-4 inhibitor, GLP-1 receptor agonist, sulfonylurea, nor basal insulin has a substantial comparative advantage when added to metformin for preventing the development or progression of DKD [diabetic kidney disease] in [type 2 diabetes] in the first decade after diagnosis,” the authors wrote. They noted that their results appear to differ from some other trials of the drugs, which were generally conducted in patients with worse kidney function at baseline. “These observations raise the possibility that GLP-1 receptor agonists are more effective at slowing the progression of established DKD than at preventing the development of DKD,” the authors wrote.