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


METHODS
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.


METHODS
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.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Christian Fynbo
CF
Christiansen
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Vera
V
Ehrenstein
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Uffe
U
Heide-Jørgensen
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Stine
S
Skovbo
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Helene
H
Nørrelund
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
Henrik Toft
HT
Sørensen
Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, Massachusetts, USA.
Lin
L
Li
Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, Massachusetts, USA.
Susan
S
Jick
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology*; D012307:Risk Factors; D006113:United Kingdom
D007004:Hypoglycemic Agents; D008687:Metformin
DIABETES & ENDOCRINOLOGY; EPIDEMIOLOGY