Metformin initiation and renal impairment: a cohort study in Denmark and the UK

Abstract

ObjectivesTo estimate prevalence of renal impairment, rate of decline in kidney function and changes in metformin use after decline in kidney function, in metformin initiators.Design, setting and participantsWe conducted this 2-country cohort study using routine data from northern Denmark and the UK during 2000–2011. We included metformin initiators among patients aged ≥30 years with medically treated diabetes.Main outcome measuresWe described patients’ demographics, comorbidity, co-medications and their estimated glomerular filtration rates (eGFR). Furthermore, we described the patients’ characteristics according to eGFR level. Finally, we examined the rate of any decline in eGFR and changes in metformin use within 90 days after first decline in eGFR during follow-up.ResultsWe included 124 720 metformin initiators in the 2 countries. Prevalence of eGFR <60 mL/min/1.73 m2 among metformin initiators was 9.0% in Denmark and 25.2% in the UK. In contrast, prevalence of eGFR values <30 mL/min/1.73 m2 among metformin initiators was 0.3% in Denmark and 0.4% in the UK. Patients with renal impairment were older and more likely to have received cardiovascular drugs. Incidence rate of decline in renal function was 4.92 per 100 person-years (95% CI 4.76 to 5.09) in Denmark and 7.48 per 100 person-years (95% CI 7.39 to 7.57) in the UK. The proportion of patients continuing metformin use, even after a first decline brought the eGFR below 30 mL/min/1.73 m2, was 44% in Denmark and 62% in the UK. There was no clinically significant dose reduction with decreasing baseline eGFR level discernible from the data.ConclusionsMild to moderate renal impairment was common among metformin initiators, while severe renal impairment was uncommon. Patients with severe renal impairment frequently continued receiving/redeeming metformin prescriptions even 90 days after eGFR decline.

Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK

“…The source population comprised residents captured by the Aarhus University Prescription Database (AUPD) in Denmark and the Clinical Practice Research Datalink (CPRD) in the UK. Both resources have been described elsewhere . The study population consisted of people with diabetes with ≥ 1 prescription(s) for glucose‐lowering agents in the AUPD or the CPRD during 2000–2011, aged ≥ 30 years at cohort entry (date of first glucose‐lowering prescription during the study period).…”

“…the UK. Both resources have been described elsewhere [9]. The study population consisted of people with diabetes with ≥ 1 prescription(s) for glucose-lowering agents in the AUPD or the CPRD during 2000-2011, aged ≥ 30 years at cohort entry (date of first glucose-lowering prescription during the study period).…”

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

“…Indeed, other authors have put forward the case for metformin to be continued with lower levels of renal function and there is some evidence that this reflects current clinical practice. [80][81][82][83] In our experience, many prescribers adopt a pragmatic approach…”

Administration of metformin in type 2 diabetes mellitus patients with chronic kidney disease; facts and myths

“…Some physicians prefer to prescribe metformin 250 mg/d to peritoneal dialysis, and 500 mg/d after each dialysis to hemodialysis patients (26). While some of the physicians in their clinical practice do not prescribe if eGFR of patient is below 30 mL/min (27). A large prospective cohort study on patients with diabetes and CKD stage 4 showed that treatment with low-dose metformin during one month revealed stable pharmacokinetics and was not associated with adverse effects (28).…”