title: Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study.
abstract: 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 metformin.
  
  
  METHODS
  Population based cohort study using routinely collected data from general practices in England.
  
  
  METHODS
  Clinical Practice Research Datalink (CPRD) database, 2004-12.
  
  
  METHODS
  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.
  
  
  METHODS
  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 m(2) (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 sulphonylureas.
  
  
  CONCLUSIONS
  Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m(2) 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 investigation.
authors.affiliation: Department of Clinical Pharmacy, Maastricht University Medical Centre, Maastricht, Netherlands Department of Clinical Pharmacy, Zuyderland MC, Heerlen, Netherlands Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: van Dalem
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: Martijn C G J
authors.initials: MC
authors.lastname: Brouwers
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Clinical Pharmacy, Zuyderland MC, Heerlen, Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Krings
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University, PO Box 80082, 3508 TB Utrecht, Netherlands.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: Department of Clinical Pharmacy, Maastricht University Medical Centre, Maastricht, Netherlands Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University, PO Box 80082, 3508 TB Utrecht, Netherlands.
authors.forename: Johanna H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Department of Clinical Pharmacy, Maastricht University Medical Centre, Maastricht, Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University, PO Box 80082, 3508 TB Utrecht, Netherlands f.devries@uu.nl.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
authors.affiliation: Department of Clinical Pharmacy, Maastricht University Medical Centre, Maastricht, Netherlands Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University, PO Box 80082, 3508 TB Utrecht, Netherlands.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Burden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000150:complications / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000453:epidemiology; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin