Hypoglycaemia is associated with increased risk of fractures in patients with type 2 diabetes mellitus: a cohort study

in European Journal of Endocrinology
Correspondence should be addressed to K A Toulis or K Nirantharakumar; Email: K.Toulis@bham.ac.uk or k.nirantharan@bham.ac.uk

*(A Ntouva and K A Toulis contributed equally to this work)

†(A A Tahrani and K Nirantharakumar are joint senior authors)

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Type 2 diabetes is associated with an increased risk of fracture. Any factor that incrementally increases this risk should be taken into account when individualising treatment. Hypoglycaemia is a common complication of antidiabetes medications and suggested as a risk factor for fractures; yet, its real-life clinical impact is unclear.


A population-based, retrospective open cohort study using routinely collected data between 1st of January 1995 and 1st of May 2016 in The Health Improvement Network (THIN) database.


Patients with type 2 diabetes mellitus with documented hypoglycaemic events were compared to randomly matched patients with type 2 diabetes mellitus without documented hypoglycaemic events matched to exposed patients on age, sex, duration of diabetes and BMI. The primary outcome was any incident fracture. Secondary outcome was incident fragility (osteoporotic) fracture.


A total of 41 163 patients with type 2 diabetes were included: 14 147 patients in the exposed cohort and 27 016 patients in the unexposed cohort. Patients with a documented hypoglycaemic event were significantly more likely to sustain any fracture compared to patients with no record of hypoglycaemic events: adjusted IRR = 1.20 (95% CI: 1.12–1.30; P < 0.0001). Patients who had a documented hypoglycaemic event were significantly more likely to suffer a fragility fracture compared to controls: adjusted IRR = 1.24 (95% CI: 1.13–1.37; P < 0.0001).


Hypoglycaemic events are a significant risk factor for fractures in patients with diabetes mellitus. This observation is clinically relevant when individualising targets for glycaemic control and selecting antidiabetic agents.

Downloadable materials

  • Supplementary Table. Read codes used to identify diabetes mellitus, hypoglycaemia and fractures.
  • Supplementary Figure 1
  • Supplementary Figure 2 (PDF 6408 KB)


     European Society of Endocrinology

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    Cumulative incidence for all fractures and fragility fractures in patients presenting with hypoglycaemia compared to patients with no record of hypoglycemia.

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