Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group:population based cohort study
Objective To determine the association
between use of sulphonylureas and risk of hypoglycaemia in relation to
renal function and sulphonylurea metabolic group compared with use of
Design Population based cohort study using routinely collected data from general practices in England.
Setting Clinical Practice Research Datalink (CPRD) database, 2004-12.
Participants 120 803 new users of a non-insulin antidiabetic agent with at least one
prescription and aged 18 years or more. The first prescription defined
start of follow-up. Patients were followed until the end of data
collection, a record for hypoglycaemia, or a blood glucose level of less
than 3.0 mmol/L.
Main outcome measures Associations between sulphonylurea dose, renal impairment, type of sulphonylurea used, and risk of hypoglycaemia, were determined using Cox proportional
hazard models. Adjustments were made for age, sex, lifestyle, comorbidity, and drug use.
Results The risk of hypoglycaemia in current users of sulphonylureas only was
significantly increased compared with current users of metformin only
(adjusted hazard ratio 2.50, 95% confidence interval 2.23 to 2.82). The
higher risk in current users of sulphonylureas only was further
increased in patients with an estimated glomerular filtration rate of
less than 30 mL/min/1.73 m2 (4.96, 3.76 to 6.55). The risk of
hypoglycaemia was also significantly higher in patients with a high
sulphonylurea dose (3.12, 2.68 to 3.62) and in current users of
glibenclamide (7.48, 4.89 to 11.44). Gliclazide, the sulphonylurea of
first choice, showed a similar risk of hypoglycaemia compared with other
Conclusions Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m2
should be considered with caution. Moreover, an increased risk of
hypoglycaemic events was observed among all users of sulphonylureas.
This contrasts with several guidelines that recommend gliclazide as
first choice sulphonylurea, and therefore requires further