Comparative effectiveness of incident oral antidiabetic drugs on kidney function

Abstract

Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who filled an incident oral antidiabetic drug prescription for metformin, sulfonylurea, or rosiglitazone, and had an estimated glomerular filtration rate (eGFR) of 60 ml/min or better. The primary composite outcome was a persistent decline in eGFR from baseline of 25% or more (eGFR event) or a diagnosis of end-stage renal disease (ESRD). The secondary outcome was an eGFR event, ESRD, or death. Sensitivity analyses included using a more stringent definition of the eGFR event requiring an eGFR <60 ml/min per 1.73 m(2) in addition to the 25% or more decline; controlling for baseline proteinuria thereby restricting data to 15,065 patients; and not requiring persistent treatment with the initial oral antidiabetic drug. Compared to patients using metformin, sulfonylurea users had an increased risk for both the primary and the secondary outcome, each with an adjusted hazard ratio of 1.20. Results of sensitivity analyses were consistent with the main findings. The risk associated with rosiglitazone was similar to metformin for both outcomes. Thus, compared to metformin, oral antidiabetic drug treatment with sulfonylureas increased the risk of a decline in eGFR, ESRD, or death.

Figure 1

Flowchart of eligible patients. eGFR, estimated glomerular filtration rate; OAD, oral antidiabetic drug; VA, Veterans Affairs.

Figure 2

Crude cumulative incidence of the composite outcome (persistent reduction of baseline estimated glomerular filtration rate of 25% or end-stage renal disease by oral antidiabetic drug exposure group).

Figure 3

Adjusted hazard ratios for the composite outcome of glomerular filtration rate event or end-stage renal disease among age, race, HbA1c, and renin–angiotensin–aldosterone system blockade subgroups. Hazard ratios greater than 1 demonstrate an increased risk for composite outcome with sulfonylurea compared with metformin. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.