This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (48)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Diabetes Mellitus  • Evidence-Based Medicine  • Adverse Effects  • Alert me on articles by topic

Systematic Review and Meta-analysis

Shelley R. Salpeter, MD; Elizabeth Greyber, MD; Gary A. Pasternak, MD; Edwin E. Salpeter, PhD

Arch Intern Med. 2003;163:2594-2602.

Background  Metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase the risk of lactic acidosis. The true incidence of fatal and nonfatal lactic acidosis associated with metformin use is not known.

Methods  A comprehensive search was performed to identify all comparative trials or observational cohort studies published between January 1, 1959, and March 31, 2002, that evaluated metformin therapy, alone or in combination with other treatments, for at least 1 month. The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years for metformin treatment and for placebo or other treatments. In a second analysis, lactate levels were measured as a net change from baseline or as mean treatment values for metformin and comparison groups.

Results  Pooled data from 194 studies revealed no cases of fatal or nonfatal lactic acidosis in 36 893 patient-years in the metformin group or in 30 109 patients-years in the nonmetformin group. Using Poisson statistics with 95% confidence intervals, the probable upper limit for the true incidence of lactic acidosis in the metformin and nonmetformin groups was 8.1 and 9.9 cases per 100 000 patient-years, respectively. There was no difference in lactate levels for metformin compared with placebo or other nonbiguanide therapies.

Conclusion  There is no evidence to date that metformin therapy is associated with an increased risk of lactic acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications.

From the Department of Medicine, Stanford University School of Medicine, Stanford, Calif (Dr S. R. Salpeter); Department of Medicine, Santa Clara Valley Medical Center, San Jose, Calif (Drs S. R. Salpeter, Greyber, and Pasternak); and Center for Radiophysics and Space Research, Cornell University, Ithaca, NY (Dr E. E. Salpeter). The authors have no relevant financial interest in this article.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Screening Adults for Type 2 Diabetes: A Review of the Evidence for the U.S. Preventive Services Task Force
Norris et al.
ANN INTERN MED 2008;148:855-868.
ABSTRACT | FULL TEXT  

Scales to Assess the Quality of Randomized Controlled Trials: A Systematic Review
Olivo et al.
ptjournal 2008;88:156-175.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2008
American Diabetes Association
Diabetes Care 2008;31:S12-S54.
FULL TEXT  

The Safety of Metformin in Heart Failure
Roberts and Ryan
The Annals of Pharmacotherapy 2007;41:642-646.
ABSTRACT | FULL TEXT  

Effects of Medical Therapy on Insulin Resistance and the Cardiovascular System in Polycystic Ovary Syndrome
Meyer et al.
Diabetes Care 2007;30:471-478.
ABSTRACT | FULL TEXT  

Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery
Duncan et al.
Anesth. Analg. 2007;104:42-50.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2007
American Diabetes Association
Diabetes Care 2007;30:S4-S41.
FULL TEXT  

Practical Review of Oral Antihyperglycemic Agents for Type 2 Diabetes Mellitus
Koski
The Diabetes Educator 2006;32:869-876.
ABSTRACT | FULL TEXT  

Phenformin-Induced Lactic Acidosis in an Older Diabetic Patient: A recurrent drama (phenformin and lactic acidosis)
Fimognari et al.
Diabetes Care 2006;29:950-951.
FULL TEXT  

Standards of Medical Care in Diabetes-2006
American Diabetes Association
Diabetes Care 2006;29:S4-S42.
FULL TEXT  

Metformin's contraindications should be contraindicated
McCormack et al.
CMAJ 2005;173:502-504.
FULL TEXT  

Metformin's contraindications: needed for now
Fantus
CMAJ 2005;173:505-507.
FULL TEXT  

Comparative Outcomes Study of Metformin Intervention Versus Conventional Approach The COSMIC Approach Study
Cryer et al.
Diabetes Care 2005;28:539-543.
ABSTRACT | FULL TEXT  

Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure: An Observational Study
Masoudi et al.
Circulation 2005;111:583-590.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes
American Diabetes Association
Diabetes Care 2005;28:S4-S36.
FULL TEXT  

Blue acid blues
Dreykluft et al.
Nephrol Dial Transplant 2004;19:2668-2671.
FULL TEXT  

Review: metformin does not increase risk of lactic acidosis or increase lactate levels in type 2 diabetes
Kruse
Evid. Based Med. 2004;9:111-111.
FULL TEXT  

Other articles noted: 14 Nov 2003 to 30 Jan 2004
Evid. Based Nurs. 2004;7:e2-e2.
FULL TEXT