Similar Outcomes with Different Glucose-Lowering Drugs in Type 2 Diabetes

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In patients with type 2 diabetes, four different classes of glucose-lowering medications produce similar kidney outcomes at 5 years' follow-up, according to a clinical trial report in JAMA Internal Medicine.

The randomized “Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness” (GRADE) trial enrolled 5047 patients with type 2 diabetes at 36 U.S. centers. Approximately two-thirds of patients were men. The mean age was 57.2 years; hemoglobin A1c (HbA1c), 7.5; duration of diabetes, 4.2 years; and estimated glomerular filtration rate (eGFR), 94.9 mL/min/1.73 m2.

Patients were assigned to receive insulin glargine, glimepiride, liraglutide, and sitagliptin, added to metformin. Treatment continued until HbA1c exceeded 7.5%, at which point insulin therapy was started. At 5 years, the chronic eGFR slope and a composite outcome of kidney disease progression were compared among treatment groups, along with secondary outcomes.

There was no significant difference in the mean chronic eGFR slope: −2.03 mL/min/1.73 m2 per year with sitagliptin, −1.92 with glimepiride, −2.08 with liraglutide, and −2.02 with insulin glargine. Rates of the composite kidney disease outcome were 10.6%, 12.4%, 12.0%, and 11.9%, respectively. Albuminuria progression accounted for 98.4% of composite outcome events.

Secondary outcomes were also similar among treatments, including incident eGFR reductions to less than 60 mL/min/1.73 m2. No treatment-related adverse kidney events occurred.

Among patients with type 2 diabetes, free of baseline kidney diseases, 5-year kidney outcomes are comparable with various classes of glucose-lowering medications. The authors discuss their findings in the context of randomized trials of the different types of drugs [Wexler DJ, et al. Comparative effects of glucose-lowering medications on kidney outcomes in type 2 diabetes: The GRADE randomized clinical trial. JAMA Intern Med 2023; 183:705–714. doi: 10.1001/jamainternmed.2023.1487].