A Systematic Review of Metformin Therapy and Renal Outcomes in Type 2 Diabetes Mellitus

Abstract

Background : Nephropathy is an important sequelae of diabetes. Current clinical study of the potential nephroprotective effects of metformin in diabetes is small and outcomes of individual studies insufficient to arrive at a firm conclusion. The objective of this systematic review is to evaluate the relationship between metformin treatment and specific renal outcomes in patients with Type 2 Diabetes Mellitus (T2DM). Methods : Two authors independently performed comprehensive searches in relevant health care databases using pre-determined search terms. Included articles described metformin treatment compared to control group(s) whereby baseline and follow-up parameters of relevant renal outcome were adequately described. Study characteristics, outcomes, and methodological quality were extracted according to standard protocols. Results : Initial search yielded 1,147 articles of which 7(6 prospective and 1 retrospective) studies meeting inclusion criteria were included in the overall analysis totaling 62,993subjects exposed to metformin. Comparators included thiazolidinediones (TZDs), sulfonylureas (SUs) and insulin in studies spanning 12 weeks to 4 years. When change from baseline values is compared, metformin demonstrated a more pronounced increase in albumin to creatinine ratio (ACR) than SUs (mean difference [MD] 14.8 mg/g [-4.2 to 25]), while TZDs were consistently associated with improvements. No significant difference in glomerular filtration rate (eGFR) was observed between metformin and TZD (MD 0.22 mL/min [-0.24 to 0.68]), while data between metformin and SU was conflicting. Conclusions : The potential nephroprotective effects of metformin in diabetes patients with or without evidence of pre-existing proteinuria are not supported by our findings. Further long-term prospective study among larger populations is needed.