Avosentan reduces albuminuria when added to standard treatment in patients with type 2 diabetes and overt nephropathy, but induces significant fluid overload and congestive heart failure, according to recent study results.
In the study, nearly 1,400 subjects with type 2 diabetes took oral avosentan 25 mg or 50 mg, or placebo each day, in addition to continued ACE inhibitor and/or angiotensin receptor blocker (ARB) therapy.
Avosentan significantly reduced the albumin-to-creatinine ratio (ACR). The median ACR decreases were 44.3%, 49.3%, and 9.7% in the 25 mg/day, 50 mg/day, and placebo groups, respectively, researchers reported in the Journal of the American Society of Nephrology (2010;21:527-535).
The investigators ended the trial prematurely after a median follow-up of four months because adverse events—mainly fluid overload and congestive heart failure—led to the discontinuation of avosentan at a significantly higher rate than the discontinuation of placebo.
The results suggest that lower doses of avosentan may have a more favorable risk/benefit ratio.