Endocrine Abstracts (2017) 49 GP84 | DOI: 10.1530/endoabs.49.GP84

Antidiabetic medication use and the risk of fracture in type 2 diabetic patients: a nested case-control study

Eladio Losada1, Berta Soldevila2,3, M. Sanni Ali4, Daniel Martinez-Laguna5, Xavier Nogués6,7, Adolfo Diez-Perez6,7, Manel Puig-Domingo2,3, Dídac Mauricio2,3 & Daniel Prieto-Alhambra4,5

1Section of Endocrinology, Hospital Can Misses, Ibiza, Spain; 2Department of Endocrinology and Nutrition. University Hospital & Health Sciences Research Institute “Germans Trias i Pujol”, Badalona, Spain; 3CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM). Carlos III Institute of Health, Madrid, Spain; 4Oxford NIHR Musculoskeletal Biomedical Research Unit. Nuffield Department of Orthopaedics. Rheumatology and Musculoskeletal Sciences. University of Oxford., Oxford, UK; 5GREMPAL Research Group. IDIAP Jordi Gol Primary Care Research Institute. Autonomous University of Barcelona, Barcelona, Spain; 6Internal Medicine Department. IMIM (Hospital del Mar Research Institute). Autonomous University of Barcelona, Barcelona, Spain; 7Cooperative Research Network on Aging and Fragility (Spanish acronym: RETICEF). Carlos III Institute of Health, Madrid, Spain.

Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures. Anti-diabetic oral agents and insulin may also impact on fracture risk. There is however scarce data available on the effect of such therapies combined as usually prescribed in real-life practice conditions.

Objectives: The objective of this study was to compare the risk of fracture among T2DM patients who are users of different antidiabetic treatments.

Methods: A nested case-control study was conducted using incident T2DM patients registered in computerised primary care records in the Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) between 2006–2012, with follow-up available until end/2013. Each case (incident fractures of the hip, spine, wrist, or proximal humerus in 2006–2013) was risk-set matched with five controls of the same gender, calendar year of T2DM diagnosis and age at index date (±10 years). Study exposure included metformin mono-therapy (reference category) and other antidiabetic medications (alone or in combination as prescribed in actual practice) in the 180 days before the index date. Conditional logistic regression analysis was used to estimate odds ratios and 95% confidence interval adjusting for the following confounders: age, gender, HbA1c level, body mass index, history of fracture, co-morbidities, and concomitant medication use.

Results: Data on 12,277 T2DM patients (2,049 cases and 10,2280 controls) was analysed. Insulin use was associated with increased fracture risk (adj OR 1.63 [95%CI 1.30–2.04]), as was the combination of metformin + sulphonylureas (adj OR 1.29 [1.07–1.56]). No significant association was found with other antidiabetic medications and/or combinations.

Discussion: Insulin and sulphonylureas use appear to be associated with an increased fracture risk when compared to metformin amongst recently diagnosed T2DM patients. Residual confounding cannot be ruled out, and more studies are needed to confirm these findings. Given their impact, risk of fracture should be taken into account in the management of T2DM patients.