Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.
BACKGROUND
Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide.


METHODS
We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations.


RESULTS
From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk.


CONCLUSIONS
In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.
Division of Nephrology, Department of Medicine, University of Western Ontario, London, Canada. mweir@uwo.ca
Matthew A
MA
Weir
Tara
T
Gomes
Muhammad
M
Mamdani
David N
DN
Juurlink
Daniel G
DG
Hackam
Jeffrey L
JL
Mahon
Arsh K
AK
Jain
Amit X
AX
Garg
D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000453:epidemiology*; D007677:Kidney Function Tests; D008297:Male; D008687:Metformin / Q000009:adverse effects; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D005905:Glyburide