The Effectiveness and Safety of Metformin Compared to Sulfonylureas in Diabetic Nephropathy: A Systematic Review

Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against using these drugs in severe diabetic kidney disease. Consequently, the choice of anti-diabetic medicine in various stages of diabetic nephropathy should balance the benefits and risks to the patient. We aim to synthesize available evidence on the effectiveness and safety of metformin concerning sulfonylureas in patients with diabetic renal disease. The COSMOS-E (Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology) and MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology) guidelines were followed when designing the systematic review. The present study assessed the effectiveness of metformin and sulphonylurea monotherapy regarding renal function. Studies published from 2001 to 2022 were included. We have identified 570 records from PubMed, BioMed Central, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ScienceDirect, and PLoS (The Public Library of Science) Medicine databases. Eight cohort studies met the inclusion criteria. All studies reported adjusted hazard ratios with confidence limits. Metformin was found to be more effective in the following events: all-cause mortality, GFR (glomerular filtration rate), ESRD (end-stage renal disease) or death events, one-year risk of death or end-stage renal disease, cardiovascular events, heart failure hospitalization, and hypoglycemic episodes. However, metformin was less effective in acute renal replacement therapy, end-stage renal disease, and/or death, with a one-year risk of acute dialysis. Lactic acidosis was not significant with metformin. The present study recommends that metformin therapy is safe compared to sulfonylurea therapy in diabetic nephropathy patients, provided that the contraindications given in the guidelines are strictly adhered to.