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.

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

“…[75]. We will briefly discuss the benefit/risk balance of metformin in T2DM patients with CV disease, in patients with RI and in the elderly population.…”

“…There are more and more data suggesting that meformin can be used in stable mild to moderate CKD and that not prescribing metformin in these patients may cause more harm (no optimal protection against CV disease, for instance) compared to the benefits of avoiding potentially rare complications (in this case, lactic acidosis) [75,88,89]. These observations led to a recent position statement in which metformin may be used down to a GFR of 30 mL/min, with dose reduction advised at 45 mL/min ( Figure 2) [3,82].…”

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

“…Metformin is eliminated renally, and cases of lactic acidosis have been described in patients with renal failure. 123 There is an ongoing debate, however, as to whether these thresholds are too restrictive and that those with mildmoderate renal impairment would gain more benefit than harm from using metformin. 124,125 In the U.K., the National Institute for Health and Clinical Excellence (NICE) guidelines are less proscriptive and more evidence-based than those in the U.S., generally allowing use down to a GFR of 30 mL/min, with dose reduction advised at 45 mL/ min.…”

Guidelines on the use of iodinated contrast media in patients with kidney disease 2012: digest version

“…Although the recommended measures vary among guidelines, most guideline documents do not recommend the suspension of biguanides in patients with normal kidney function before the use of iodinated contrast media [29][30][31] ( Table 2). …”