Metformin as a means to reduce mortality in critical illness

Posted by Biome on 10th September 2013 - 0 Comments

Metformin is widely prescribed in type 2 diabetes and previous studies have also suggested that it may improve in outcomes in critical illness. New research published in Critical Care, led by Henrik Toft Sørensen of Aarhus University Hospital, Denmark has found that in patients with type 2 diabetes, use of metformin before admission to an intensive care unit (ICU) is associated with reduced 30-day mortality.

Sørensen and colleagues conducted a cohort study looking at the association between pre-admission metformin use and mortality after ICU admission. Using the unique Danish Civil Registration Number assigned to each citizen, data was collected by individual-level linkage between population based medical registries and databases. All 52,964 adult patients admitted to a medical or surgical ICU in Northern Denmark between January 2005 and December 2011 were identified. Of these patients, 7,404 had type 2 diabetes. Prescription data for anti-diabetic medication, including metformin was collected for each patient. 1,073 were taking metformin alone and 1,335 metformin in combination with other anti-diabetic drugs. Patients were followed up from the date of ICU admission for 30 days (or death if sooner). 30-day mortality was calculated and current metformin use was compared to recent use, former use, and never use.

Current metformin users had a lower 30-day mortality compared to non-users. 30-day mortality in non-users was 25 percent, compared to 17.6 percent for those on metformin monotherapy and 17.9 percent for those on metformin in combination with other anti-diabetics. This reduced mortality persisted after adjustment for pre-admission morbidity and other potential confounders, and was only seen in patients who were currently using metformin. Mortality was not associated with recent or former metformin use. No difference in mortality was observed between those on other anti-diabetic drugs and those who did not use any anti-diabetic drugs.

The reasons for this reduced mortality are not clear. One potential explanation is that, in addition to lowering blood glucose, metformin has other effects that may be beneficial during critical illness. It has anti-inflammatory effects that may modulate the hyper-inflammatory response central to the early phase of sepsis and organ dysfunction, as well as anti-thrombotic effects that could prevent microvascular thrombosis.

Although this study suggests that ICU patients may benefit from pre-admission metformin, the safety and effect of using metformin during critical illness is unclear. Metformin is generally not recommended during hospitalization due to the potential risk of lactic acidosis in patients with severe renal, liver or heart disease, or in patients with shock or post major surgery. It is therefore frequently switched to insulin on admission to hospital. The effect observed in the study is therefore likely due to mediation of the early response to critical illness.

This study suggests that use of metformin, alone or in combination with other anti-diabetic drugs, before admission to an ICU, is associated with reduced 30-day mortality. However, more work is needed to understand and balance the potential risks of lactic acidosis with any potential benefits of metformin in critical illness.



Preadmission metformin use and mortality among intensive care patients with diabetes: a cohort study

Christiansen CF, Johansen MB, Christensen S, O’Brien JM, Tønnesen E and Sørensen HT
Critical Care 2013, 17:R192

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