Does Metformin Increase the Risk of Fatal or Nonfatal Lactic Acidosis?

作者：Cayley William E Jr^*

来源：American Family Physician, 2010, 82(9): 1068-1070.

Background: Metformin is an oral antihyperglycemic agent that has been shown to reduce total mortality compared with other antihyperglycemic agents in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic, and pulmonary diseases, and, advancing age.
Objectives: To assess the incidence of fatal and nonfatal lactic acidosis and to evaluate blood lactate levels for those on metformin treatment compared with placebo or non-metformin therapies.
Search Strategy: A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators.
Selection Criteria: Prospective trials and observational cohort studies in patients with type 2 diabetes of at least one month's duration were included if they evaluated metformin, alone or in combination with other treatments, compared with placebo or any other glucose-lowering therapy.
Data Collection and Analysis: The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis, lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference in mmol per L, using the fixed-effect model for continuous data.
Main Results: Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patient-years in the non-metformin group. Using Poisson statistics, the upper limit for the true incidence of. lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared with non-metformin therapies.
Authors' Conclusions: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis or with increased levels of lactate compared with other antihyperglycemic treatments.

• 出版日期2010-11-1