Highlights
- •Risk of severe hypoglycemia, requiring hospitalization, associated with sulfonylurea use was assessed.
- •Severe hypoglycemia risk was 4.5 times higher among patients initiating sulfonylurea compared with patients initiating metformin.
- •An alternative antidiabetic agent to sulfonylurea may be warranted when metformin is contraindicated.
Abstract
Purpose
The magnitude of the risk of severe hypoglycemia associated with sulfonylureas as
the initial treatment for type 2 diabetes in the real-world setting is unknown. We
assessed the risk of severe hypoglycemia associated with initiating monotherapy with
sulfonylurea compared with metformin for the treatment of type 2 diabetes.
Methods
By using the UK Clinical Practice Research Datalink and Hospital Episode Statistics
linked to the Office for National Statistics, we identified a cohort of patients with
type 2 diabetes who initiated sulfonylureas or metformin monotherapy between April
1, 1998, and December 31, 2012, with follow-up until December 31, 2013. Sulfonylurea
users were matched one-to-one to metformin users by high-dimensional propensity scores.
Hazard ratios (HRs) and 95% confidence intervals (CIs) of severe hypoglycemia, defined
as requiring hospitalization, were estimated using Cox proportional hazards models
comparing sulfonylureas with metformin monotherapy.
Results
The study cohort consisted of 14,012 initiators of sulfonylureas matched to 14,012
initiators of metformin. The mean treated follow-up time was 1.41 (standard deviation,
1.84) years. Use of sulfonylurea was associated with an elevated incidence of severe
hypoglycemia compared with metformin as the initiating monotherapy for type 2 diabetes
(incidence rate, 2.4/1000 person-years; 95% CI, 1.90-2.90; HR, 4.53; 95% CI, 2.76-7.45).
Conclusions
Sulfonylureas, when prescribed as the initiating monotherapy for the treatment of
type 2 diabetes, is associated with a 4.5-fold increase in the risk of severe hypoglycemia.
Given the negative consequences of this outcome, clinicians should consider alternative
hypoglycemic agents when metformin is not tolerated or contraindicated.
Keywords
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Article info
Publication history
Published online: October 13, 2017
Footnotes
Funding: This study was funded in part by grants from the Canadian Institutes of Health Research (CIHR MOP-49462), Canada Foundation for Innovation (CFI 94480), and Boehringer Ingelheim. The sponsors had no role in the design of the study, the analysis and interpretation of the data, or the preparation and approval of the manuscript. Boehringer Ingelheim was invited to comment on the study protocol and the manuscript.
Conflicts of Interest: SS has received research grants and participated in advisory board meetings or as a speaker at conferences for AstraZeneca, Bayer Pharma, Boehringer-Ingelheim, Bristol-Myers-Squibb, Merck, and Novartis.
Authorship: All authors had access to the data and played a role in writing this manuscript.
Identification
Copyright
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