HbA1c, Antidiabetic Treatment and Risk of Fracture in Type 2 Diabetes

Sarfaroj Khan 


November 17, 2020


  • Type 2 diabetes (T2D) patients with glycated haemoglobin (HbA1c) levels of <8.0% who were currently exposed to metformin monotherapy were at a lower risk of fracture compared with those not currently exposed to an antidiabetic drug.

  • In contrast, the risk of fracture in patients receiving intensified treatment was not or only slightly associated with glycaemic control.

Why this matters

  • Findings confirm that metformin is safe in terms of skeletal changes and predominantly exerts its beneficial effect on the risk of fracture in an early and well-controlled disease stage.

Study design

  • This nested case-control study included 8809 patients with T2D and fracture and 35,219 matched control participants from the UK Clinical Practice Research Datalink database (1995-2017).

  • The association between the level of glycaemic control, antidiabetic treatment and risk of low-trauma fractures was evaluated.

  • Funding: Swiss National Science Foundation.

Key results

  • Patients with current metformin use and HbA1c levels ≤7.0% were at a lower risk of fractures than those not using any antidiabetic medication (adjusted OR [aOR], 0.89; 95% CI, 0.83-0.96).

  • Risk reduction was marginally stronger for those with HbA1c levels of 7.0-8.0% (aOR, 0.81; 95% CI, 0.73-0.90).

  • Patients receiving metformin with HbA1c levels >8.0% had a risk of fracture similar to patients not using any antidiabetic drugs (aOR, 0.95; 95% CI, 0.81-1.10).

  • The level of glycaemic control was not associated with the risk of fracture in patients with current use of first intensification treatment.

  • The level of glycaemic control in patients with current use of second intensification treatment showed an association with the risk of fracture.

    • HbA1c levels ≤7.0% (aOR, 1.32; 95% CI, 1.18-1.49).

    • HbA1c levels >7.0 to ≤8% (aOR, 1.26; 95% CI, 1.13-1.41).

    • HbA1c levels >8.0% (aOR, 1.13; 95% CI, 1.02-1.25).


  • Possibility of missing some unrecorded fracture cases.

  • Study did not analyse the cause of the fracture.


Charlier S, Vavanikunnel J, Becker C, Jick SS, Meier C, Meier CR. Antidiabetic treatment, level of glycemic control, and risk of fracture in diabetes type 2: A nested case-control study. J Clin Endocrinol Metab. 2020 Nov 3 [Epub ahead of print]. doi: 10.1210/clinem/dgaa796. PMID: 33141149 View abstract

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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