In patients with type 2 diabetes and predominantly normal renal function, renal outcomes were similar across four different antidiabetic drug classes.

In the landmark GRADE trial (NEJM JW Gen Med Oct 15 2022 and N Engl J Med 2022; 387:1075-1088), researchers compared kidney outcomes in 5000 people (mean age, 57 years) with type 2 diabetes who were taking metformin and who were randomised to one of four add-on therapies: insulin glargine, glimepiride (a sulfonylurea), liraglutide (a glucagon-like peptide-1 receptor agonist) or sitagliptin (a dipeptidyl peptidase-1 inhibitor). The original published report showed no difference between groups in renal outcomes at five years; now, researchers have provided additional detail.

At baseline, mean glycosylated haemoglobin (HbA_1c) was 58 mmol/mol (7.5%), mean duration of diabetes was 4.2 years and mean estimated glomerular filtration (eGFR) was 95mL/min/1.73 m²; only 2.5% of patients had eGFRs of 60mL/min/1.73m² or lower, and 16% had moderate-to-severe albuminuria. About 60% of patients were receiving renin-angiotensin-aldosterone inhibitors. After five-year follow up, mean change in eGFR was similar for all groups. Another endpoint for progression of kidney disease (i.e. a composite of increase in albuminuria stage, dialysis, transplant or death) was about 12% in all groups and almost entirely due to progression of albuminuria.

Similar results were obtained for multiple secondary outcomes (e.g. incident eGFR 60mL/min/1.73m² or lower).

Comment: In metformin-treated patients with type 2 diabetes and relatively normal kidney function, kidney outcomes were similar, regardless of which antidiabetic agent was added. Trial limitations include its relatively short duration for a low-risk population and lack of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor arm; SGLT-2 inhibitors can slow eGFR decline – with absolute benefits more likely to occur in patients who already have evidence of kidney involvement – but were not approved for use when this trial began.

Paul S. Mueller, MD, MPH, FACP, Regional Vice President – Southwest Wisconsin, Mayo Clinic Health System, La Crosse; Professor of Medicine and Biomedical Ethics, Mayo Clinic College of Medicine and Science, Rochester, USA.

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.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.