Apostolos Tsapas, MD, PhD
In patients with type 2 diabetes, does metformin increase risk for lactic acidosis compared with placebo or other glucose-lowering therapies?
Included studies compared ≥ 1 month of metformin (alone or with other therapies) with placebo or another glucose-lowering therapy in adults with type 2 diabetes mellitus. Outcomes were death due to lactic acidosis, lactic acidosis, and blood lactate levels.
Cochrane Library (issue 3, 2009), MEDLINE, EMBASE/Excerpta Medica, and REACTIONS (to Oct 2009); Cumulated Index Medicus (1959 to 1965); references of identified studies and reviews; and clinical symposium abstracts published in a single issue of Diabetologia (2000) were searched for clinical trials published in any language. Authors of identified studies and Bristol-Myers Squibb were contacted. 347 studies (n = 96 295, mean age 57 y, 61% men) met the selection criteria. 209 were prospective comparative trials, 125 were prospective cohort studies, and 13 were retrospective cohort studies. Metformin dosage was 1 to 3 g/d, titrated clinically. Comparison therapies were placebo, diet, insulin, glyburide, gliclazide, glipizide, glimepiride, chlorpropamide, tolbutamide, acarbose, nateglinide, repaglinide, miglitol, troglitazone, rosiglitazone, pioglitazone, vildagliptin, sitagliptin, saxagliptin, dapagliflozin, and guar gum. 32 trials were judged to have a low risk for bias.
No cases of fatal or nonfatal lactic acidosis were identified in the 347 studies (70 490 patient-y of metformin therapy). Based on Poisson statistics, the risk difference for metformin compared with nonmetformin therapies was 0.00 per 100 000 patient-years (95% CI −5.4 to 4.3). Metformin and nonmetformin groups did not differ for net change in blood lactate levels (7 studies, n = 222, weighted mean difference [WMD] 0.12 mmol/L, 95% CI −0.01 to 0.25) or for mean lactate levels (16 studies, n = 1387, WMD 0.04 mmol/L, CI 0.00 to 0.13).
Metformin does not increase risk for lactic acidosis compared with placebo or other glucose-lowering therapies in patients with type 2 diabetes.
Tsapas A. Review: Metformin does not increase risk for lactic acidosis in type 2 diabetes. Ann Intern Med. ;153:JC1–9. doi: 10.7326/0003-4819-153-2-201007200-02009
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Published: Ann Intern Med. 2010;153(2):JC1-9.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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