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Melillo, MD 4/10/2003
Reviewer: David Thom, MD, PhD
Evidence
• In the Cochrane systematic review, pooled data from 176 comparative trials and
cohort studies (taking account contraindications) revealed no cases of fatal or
nonfatal lactic acidosis in 35,619 patient- years of metformin use or in 30,002
patient-years in the non-metformin group. (1)
• Using Poisson statistics with 95% confidence intervals the upper limit for the true
incidence of metformin-associated lactic acidosis was 8.4 cases per 100,000
patient-years and the upper limit for the true incidence of lactic acidosis in the
non- metformin group was 9 cases per 100,000 patient-years. (1)
• The University of Pittsburgh Medical Center Presbyterian (UPMC) conducted a
case-control study of 263 hospitalizations involving 204 patients who received at
least 1 dose of metformin during inpatient admission. In this study patients in 71
admissions (27%) had at least 1 absolute contraindication to metformin at the time
of or during the time of admission. In 29 (41%) of these 71 admissions, treatment
with metformin continued despite the contraindication. (2)
• The most common contraindication, elevated serum creatinine concentration, was
present or developed during 32 admissions (12%); however, metformin use was
discontinued in only 8 of these 32 patients. (2)
1
Comments
• The Cochrane review is the most comprehensive and rigorous study examining
the potential increased risk of lactic acidosis from metformin. However, the
authors were not able to quantitatively assess the safety of metformin treatment in
the presence of each of hypoxic conditions (see table below for contraindications)
because the data excluded most contraindications and those patients with
contraindications such as renal or hepatic insufficiency who were included were
not separated into subgroups.
• The UPMC trial was only focused on whether prescribers were complying with
the labeled contraindications and precautions to the use of metformin instead of
verifying that metformin therapy causes lactic acidosis in patients at increased
risk.
Citations
Salpeter S, Greber E, Pasternak G, Salpeter EA. Risk of fatal and nonfatal lactic acidosis
with metformin use in type 2 diabetes mellitus (Cochrane Review). In: The Cochrane
Library, Issue 1, 2003. Oxford Update Software.