Angiotensin-Receptor Blockade Versus Converting-Enzyme Inhibition in Type 2 Diabetes and Nephropathy

Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J; Diabetics Exposed to Telmisartan and Enalapril Study Group. N Engl J Med. 2004;351:1952-1961.

Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been found to reduce progression of renal dysfunction in diabetic nephropathy in addition to and independent of their blood pressure lowering effects. However, there have been very few head-to-head studies of ACE inhibitors and ARBs in patients with diabetic nephropathy. Thus, the purpose of this randomized, double-blind, prospective study was to compare the renal protective effects of telmisartan, an ARB, and enalapril, an ACE inhibitor, in patients with type 2 diabetes and early nephropathy over a 5-year period.

Subjects were randomized to treatment with telmisartan 80 mg/day (n=120) or enalapril 20 mg/day (n=130). Change in glomerular filtration rate (GFR) was used to assess renal dysfunction. From baseline to year 5, mean change in GFR was –17.9 mL/min/1.73 m² in the telmisartan treatment group and –14.9 mL/min/1.73 m² in the enalapril treatment group. A difference in GFR of ≥10.0 mL/min/1.73 m² between treatment groups was predefined as being clinically significant. The treatment difference between the 2 groups was –3.0 mL/min/1.73 m² (95% CI: –7.6–1.6 mL/min/1.73 m²), which therefore showed noninferiority of telmisartan to enalapril. There was a high dropout rate of approximately one third in both treatment groups, largely attributed to adverse events. A dropout rate of 25% per year was expected based on previous reports of cardiovascular events in patients with type 2 diabetes and increased urinary albumin excretion.

In summary, telmisartan was shown to be noninferior to enalapril in the prevention of progression of renal dysfunction over a 5-year period in patients with type 2 diabetes. Both the American Diabetes Association and the Joint National Committee on Prevention, Diagnosis, and Management of Hypertension recommend an ACE inhibitor or ARB as first-line treatment in hypertensive and normotensive patients with diabetic nephropathy, and these findings are consistent with this recommendation.