et al. Ann. Intensive Care (2017) 7:116
Does metformin exposure before ICU
stay have any impact on patients’ outcome? A
retrospective cohort study of diabetic patients
, Jean‑Emmanuel Alphonsine
, Jonathan Chelly
, Ly Van Phach Vong
, Oumar Sy
, Olivier Ellrodt
, Mehran Monchi
and Christophe Vinsonneau
Background: Impact of metformin exposure before ICU stay remains controversial. Metformin is thought to induce
lactic acidosis and haemodynamic instability but may reduce ICU mortality. We evaluated its inﬂuence on outcome in
diabetic patients admitted in the ICU and then compared two diﬀerent populations based on the presence of septic
Methods: We conducted a retrospective cohort study in a 24‑bed French ICU between October 2010 and December
2013, including all ICU‑admitted diabetic patients.
Results: Among 635 diabetic patients admitted during the study period, 131 (21%) were admitted with septic shock.
Multivariate analysis showed no diﬀerence in hospital mortality in all metformin users (OR 0.75 [95% CI 0.44–1.28];
p = 0.29), except in the septic shock subgroup (OR 0.61; 95% CI [0.37–0.99]; p = 0.04) despite higher vasopressor
dosages in the ﬁrst hours after shock onset. Blood lactate level was higher in metformin users than in non‑metformin
users in all patients (p < 0.001), in septic shock patients (p < 0.001) and in patients without kidney injury (p < 0.001).
Metformin users did not have more septic shock from unknown aetiology (p = 0.65) or unknown pathogen
(p = 0.99).
Conclusions: Metformin use before admission to ICU did not aﬀect in‑hospital mortality. However, for patients with
septic shock, mortality was lower, despite worse clinical presentation on admission. Blood lactate levels were always
higher with or without septic shock and indiﬀerent of kidney function.
Keywords: Metformin, Septic shock, Diabetes, Lactic acidosis, ICU
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Metformin is increasingly used as an oral antidiabetic
(OAD) agent, especially in patients with type 2 diabetes
mellitus. Metformin inhibits hepatic glucose production,
reduces intestinal glucose absorption and improves glu
cose metabolism .
Its use is associated with a reduction in cardiovascu
lar morbidity and mortality, in comparison with insu-
lin, other OADs or diet alone, in non-acutely ill patients
[2, 3]. It is thought to induce or worsen lactic acidosis,
especially in acute renal or liver dysfunction . But in
a recent meta-analysis pooling 347 trials involving long-
run metformin use, the authors found no case of met
formin-associated lactic acidosis (MALA), as well as no
diﬀerence in blood lactate level related to metformin use
. ese results were conﬁrmed in a large cohort of
diabetic patients treated with metformin despite various
metformin contraindications, in which no MALA has
been described by the authors .
In the ICU, MALA has been described in renal, liver,
pulmonary or cardiovascular chronic failure , and
several case reports described fatal or non-fatal MALA
in acute conditions. In contrast, a recent retrospective
Département de Médecine Intensive et Unité de Recherche Clinique,
Groupe Hospitalier Sud Ile‑de‑France, Hôpital de Melun, 77000 Melun,
Full list of author information is available at the end of the article