Metformin and lactic acidosis in an Australian community setting: the Fremantle Diabetes Study.
OBJECTIVE
To determine the incidence of lactic acidosis in community-based patients with type 2 diabetes, with special reference to metformin therapy.


METHODS
Substudy within a longitudinal observational study, the Fremantle Diabetes Study (FDS).


METHODS
1279 patients from a postcode-defined population of 120 097 people in Western Australia.


METHODS
Confirmed hospitalisation with lactic acidosis identified through the WA Data Linkage System during two periods: (1) from study entry, between 1993 and 1996, and study close in November 2001; and (2) from study entry to 30 June 2006.


RESULTS
At entry, 33.3% of patients were metformin-treated, and 23.1% of these had one or more contraindications to metformin (55.1% and 38.0%, respectively, after 5 years' follow-up). Five confirmed cases of lactic acidosis were identified during 12 466 patient-years of observation; all had at least one other potential cause, such as cardiogenic shock or renal failure. From study entry to close, the incidence was 0/100,000 patient-years in both metformin-treated and non-metformin-treated patients. Between study entry and 30 June 2006, incidence was 57/100,000 patient-years (95% CI, 12-168) in metformin-treated patients and 28/100,000 patient-years (95% CI, 3-100) in the non-metformin-treated group, an incidence rate difference of -30 (-105 to 46) (P=0.4).


CONCLUSIONS
The incidence of lactic acidosis in patients with type 2 diabetes is low but increases with age and duration of diabetes, as cardiovascular and renal causes become more prevalent. Metformin does not increase the risk of lactic acidosis, even when other recognised precipitants are present.
Kamber
Niklaus
N
School of Medicine and Pharmacology, University of Western Australia, Fremantle, WA.
Davis
Wendy A
WA
Bruce
David G
DG
Davis
Timothy M E
TM
D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000453:epidemiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014904:Western Australia / Q000453:epidemiology
D007004:Hypoglycemic Agents; D008687:Metformin