Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Abstract

Metformin is unanimously considered as the first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of the presence of numerous contraindications corresponding to situations that may increase the risk of lactic acidosis. Various observational data from real life showed that many diabetic patients considered as "at risk" still receive metformin, often without appropriate dose adjustment, apparently without any harm, especially no increased risk of lactic acidosis. More interestingly, recent data suggest that type 2 diabetes patients who are considered as being "at risk" because of the presence of traditional contraindications still take benefit from metformin therapy, with a reduction of morbidity and mortality compared with other glucose-lowering agents, more particularly sulfonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that may theoretically increase the risk of lactic acidosis. A special attention will be devoted to elderly patients with type 2 diabetes. Indeed, this population is growing rapidly and older patients may cumulate several comorbidities

The rs10885122 polymorphism of the adrenoceptor alpha 2A (ADRA2A) gene in Euro-Brazilians with type 2 diabetes mellitus

“…T2D is a polygenic disease, and several single nucleotide polymorphisms (SNPs) have been associated with risk or protection regarding this disease and its complications (3)(4)(5).…”

Lactic Acidosis in a Man with Diabetes: Is Metformin the Culprit?

“…Similarly metformin is contraindicated in liver failure, advanced heart failure or respiratory insufficiency, all of which are recognized risk factors for systemic hypoxia and lactic acidosis [21]. All these are recognized risk factors for metformin associated lactic acidosis [3].…”

Drugs for the Treatment of Type II Diabetes: A Visit to the Past and a Look to the Future

“…Felizmente a incidência bastante baixa (um caso a cada 33.000 pacientes) não impede seu emprego clínico, mas é motivo de preocupação e atenção por médicos e pacientes, principalmente naqueles com alguma predisposição ao quadro de acidose. 18,19 …”