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Diabetes Obes Metab. 2019 Jan;21(1):52-60. doi: 10.1111/dom.13480. Epub 2018 Aug 28.

Sodium-glucose co-transporter-2 inhibitors and the risk of fractures of the upper or lower limbs in patients with type 2 diabetes: A nested case-control study.

Author information

1
Institute for Applied Health Research Berlin (InGef), Berlin, Germany.
2
University Medicine Berlin (Charité), Institute for Social Medicine, Epidemiology and Health Economics, Berlin, Germany.
3
Frank Andersohn Consulting & Research Services, Berlin, Germany.
4
Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.

Abstract

AIMS:

To investigate whether the use of SGLT-2 inhibitors is associated with an increased risk of fractures.

MATERIAL AND METHODS:

We conducted a cohort study with nested case-control analysis based on the InGef database between November 2011 and December 2016 among patients with type 2 diabetes who were initiating treatment with, switching to, or adding a new class of non-insulin antidiabetic drug. Patients with a hospital or ambulatory diagnosis of fractures of the upper or lower limbs were included and were matched to up to 40 randomly sampled control subjects. Conditional logistic regression was used to estimate confounder adjusted odds ratios (ORs) of fractures, comparing current use of metformin plus SGLT-2 inhibitor or metformin plus another antidiabetic drug class to metformin plus DPP-4 inhibitor as reference.

RESULTS:

The cohort comprised 210 042 new users of non-insulin antidiabetic drugs. For the nested case-control analysis, 7522 patients with fractures were matched to 296 845 control subjects. In the crude and confounder adjusted analyses, current use of metformin plus SGLT-2 inhibitor compared to current use of metformin plus DPP-4 inhibitor was not associated with fractures (OR: 1.00; 95% CI: 0.72-1.39 and OR: 0.99; 95% CI: 0.71-1.37, respectively). Similarly, no statistically significant association was found for current use of metformin plus another antidiabetic drug class. No treatment effect modification was observed after stratification by number of documented risk factors for falls and fractures (< 4 vs ≥ 4) and age (< 75 vs ≥ 75 years).

CONCLUSION:

Our study suggests that use of SGLT-2 inhibitors and other antidiabetic drug classes are not associated with an increased risk of fractures of the upper or lower limbs compared to use of DPP-4 inhibitors in patients with type 2 diabetes.

KEYWORDS:

Germany; bone; claims data; diabetes mellitus; fractures; hypoglycaemic agents ; type 2

PMID:
30047217
DOI:
10.1111/dom.13480

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