Aims: Epidemiological and experimental data suggest that activation of the oestrogen receptor pathway limits the incidence and the progression of diabetic nephropathy. We tested the hypothesis that raloxifene protects against increasing urinary albumin excretion in post-menopausal women with Type 2 diabetes in a randomized pilot clinical trial.
Methods: We included 39 post-menopausal women with Type 2 diabetes and micro- or macro-albuminuria in a 6-month, double-blind, placebo-controlled trial: 20 received placebo and 19 received 60 mg raloxifene per day. The albumin : creatinine ratio (ACR) in urine was determined on three consecutive days during the week before randomization and during the week before the final visit.
Results: One patient in each group dropped out in the first 3 weeks, leaving 37 patients for the analysis (19 on placebo and 18 on raloxifene). From randomization to the final visit, mean ACR was unchanged in the placebo group {277 microg/mg (67; 651) [median (interquartile range)] vs. 284 microg/mg (79; 1508)} but decreased slightly in the raloxifene group [376 microg/mg (67; 615) vs. 243 microg/mg (103; 549)]. This corresponds to a change of +24 (-37; +517) for the placebo group vs. -10 microg/mg (-36; +16) for the raloxifene group (P = 0.11). In multivariate analysis, raloxifene treatment (P(adjusted) = 0.013), baseline low-density lipoprotein (LDL) cholesterol (P(adjusted) = 0.023) and change in LDL cholesterol (P(adjusted) = 0.008) were related to the absolute change in ACR. Adverse effects were similar in the two groups.
Conclusions: These results suggest that raloxifene may limit the progression of albuminuria in post-menopausal women with diabetes; further studies in a larger population are warranted.