To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function.
Observational study between July 2004 and December 2010, mean follow-up 3.9 years.
Hospital outpatient clinics and primary care in Sweden.
51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin.
Main outcome measures
Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression.
Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45–60 ml/min/1.73 m2, and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30–45 ml/min/1.73 m2.
Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.
To evaluate the risks of CVD, acidosis/serious infection and mortality associated with metformin and other glucose-lowering treatments, in a cohort of 51 675 type 2 diabetes patients and in subgroups with different degrees of renal impairment.
Metformin was associated with reduced risk of CVD, acidosis/serious infection and all-cause mortality compared with insulin and a reduced risk of all-cause mortality compared with other OHAs.
The effects were consistent in patients with renal impairment (eGFR 45–60 ml/min/1.73 m2), and there were no increased risk of acidosis/serious infection even in patients with low renal function (eGFR 30–45 ml/min/1.73 m2).
Strengths and limitations of this study
A large cohort with comprehensive data on patient characteristics was studied.
A composite end point including diagnosis of acidosis, shock, acute renal failure and serious infections was used to evaluate the occurrence of lactic acidosis.