title: Contraindications can damage your health--is metformin a case in point?
abstract: Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.
authors.affiliation: Clinic Lippe, First Department of Medicine, Detmold, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Holstein
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D000375:Aging; D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006331:Heart Diseases; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015994:Incidence; D019344:Lactic Acid / Q000097:blood; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin