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

Journal: BMJ Open

Authors: Christian Fynbo ChristiansenVera EhrensteinUffe Heide-JørgensenStine SkovboHelene NørrelundHenrik Toft SørensenLin LiSusan Jick

NLM Citation: Christiansen CF, Ehrenstein V, Heide-Jørgensen U, Skovbo S, Nørrelund H, Sørensen HT, Li L, Jick S. Metformin initiation and renal impairment: a cohort study in Denmark and the UK. BMJ Open. 2015 Sep 2;5(9):e008531. doi: 10.1136/bmjopen-2015-008531. PMID: 26338686; PMCID: PMC4563232.

Abstract

Objectives: To 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 participants: We 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 measures: We 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.

Results: We included 124,720 metformin initiators in the 2 countries. Prevalence of eGFR <60 mL/min/1.73 m(2) 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 m(2) 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 m(2), 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.

Conclusions: Mild 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.

Keywords: DIABETES & ENDOCRINOLOGY; EPIDEMIOLOGY.