Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2016 Jul 13:354:i3625.
doi: 10.1136/bmj.i3625.

Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study

Judith van Dalem  1 , Martijn C G J Brouwers  2 , Coen D A Stehouwer  3 , André Krings  4 , Hubert G M Leufkens  5 , Johanna H M Driessen  6 , Frank de Vries  7 , Andrea M Burden  6
Affiliations
Comparative Study

Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study

Judith van Dalem et al. BMJ. .

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.

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 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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: HGML receives no direct funding or donations from private parties, including the pharmaceutical industry. Research funding from public-private partnerships, ie, IMI and TI Pharma (www.tipharma.nl), has been accepted under the condition that no company specific product or company related study is conducted. He has received unrestricted research funding from the public sources, ie, the Netherlands Organisation of Health Research and Development (ZonMW), the EU 7th Framework Program (FP7), the Dutch Medicines Evaluation Board (MEB), the National Health Care Institute (ZIN), and the Dutch Ministry of Health. Other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. International Diabetes Federation. About diabetes, 2015. www.idf.org/.
    1. World Health Organization. Health topic - Diabetes Mellitus, 2015. www.who.int/topics/diabetes_mellitus/en/.
    1. Ashcroft FM. Mechanisms of the glycaemic effects of sulfonylureas. Horm Metab Res 1996;28:456-63. 10.1055/s-2007-979837 pmid:8911983. - DOI - PubMed
    1. Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycaemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev 2001;17:467-73. 10.1002/dmrr.235 pmid:11757083. - DOI - PubMed
    1. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc 1996;44:751-5. 10.1111/j.1532-5415.1996.tb03729.x pmid:8675920. - DOI - PubMed

Publication types

MeSH terms