Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register

Abstract

ObjectiveTo 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.DesignObservational study between July 2004 and December 2010, mean follow-up 3.9 years.SettingHospital outpatient clinics and primary care in Sweden.Participants51 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 measuresRisks 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.ResultsCompared 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.ConclusionsMetformin 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.

Clarifying the relationship between metformin, acute kidney injury and lactic acidosis

“…Finally, we do not agree with the recommendation made by C. Rhee and K. KalantarZadeh that the use of metformin should be restricted in patients with chronic kidney disease (CKD), particularly in view of the increasing evidence base that supports metformin safety in patients with CKD 4,5 . We eagerly await further pharmacokinetic studies on the safety and efficacy of metformin in these patients.…”

Metformin in advanced chronic kidney disease: are current guidelines overly restrictive?

“…In a prospective observational study, Ekström et al examined metformin therapy in 51,675 patients with type 2 diabetes and differing levels of renal function (eGFR 30-44 mL/min, 45-59 mL/min and ≥60 mL/min). 34 In this study, metformin-based therapy was not associated with a reduced risk of CVD when compared with other therapies, independent of renal function.…”

“…In the aforementioned study by Ekström et al, metformin prescription was not associated with an increased risk of acidosis or serious infection in patients with an eGFR of 30-44 mL/min when compared with other hypoglycaemic treatments. 34 Conversely, metformin was associated with a significantly lower risk of this composite outcome compared with other agents in those with an eGFR ≥45 mL/min. In a recent study by Hung et al, metformin use in 3,254 patients with advanced CKD approaching ESRD (creatinine >530 μmol/L) was not associated with a significantly greater risk of metabolic acidosis (adjusted HR 1.30, 95% CI 0.88 to 1.93).…”

Metformina en enfermedad renal diabética: estado actual

“…Más aún, en comparación con las sulfonilureas, el uso de metformina está asociado con una menor probabilidad de deterioro de la función renal 33 .…”