Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study.
OBJECTIVE
The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark.


METHODS
All patients aged ≥ 30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi- or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality.


RESULTS
A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p = 0.02), metformin + sulfonylurea 0.89 (95% CI 0.82-0.96, p = 0.003), metformin + insulin 0.96 (95% CI 0.82-1.13, p = 0.6), metformin + insulin + sulfonylurea 0.94 (95% CI 0.77-1.15, p = 0.5), sulfonylurea + insulin 0.97 (95% CI 0.86-1.08, p = 0.5) and insulin 1.14 (95% CI 1.06-1.20, p = 0.0001).


CONCLUSIONS
Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.
Andersson
C
C
Department of Cardiology, Gentofte University Hospital, Niels Andersens Vej 65, 2900 Hellerup, Denmark. ca@heart.dk
Olesen
J B
JB
Hansen
P R
PR
Weeke
P
P
Norgaard
M L
ML
Jørgensen
C H
CH
Lange
T
T
Abildstrøm
S Z
SZ
Schramm
T K
TK
Vaag
A
A
Køber
L
L
Torp-Pedersen
C
C
Gislason
G H
GH
D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D058065:Diabetic Cardiomyopathies / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000209:etiology / Q000401:mortality* / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D016019:Survival Analysis
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin