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Clin Ther. 2017 Nov;39(11):2296-2310.e14. doi: 10.1016/j.clinthera.2017.09.016. Epub 2017 Nov 4.

Factors Associated with Type 2 Diabetes Mellitus Treatment Choice Across Four European Countries.

Author information

PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands. Electronic address:
PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands.
Grimsdyke House, London, United Kingdom.
Grup de Recerca en Malalties Prevalents de l'Aparell Locomotor (GREMPAL) Research Group and Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFes), Idiap Jordi Gol Primary Care Research Institute, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.
Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy.
AstraZeneca R&D, Mölndal, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.



The aim of this analysis was to identify factors associated with the choice of type 2 diabetes mellitus (T2DM) therapy at the time of intensification of antidiabetic treatment across 4 European countries.


Antidiabetic drug prescription/dispensing records and patients' characteristics were obtained from the electronic health care records of patients with T2DM from the Netherlands (NL), Italy, and Spain (ES) (all, 2007-2011); and the United Kingdom (UK; 2008-2012). Oral monotherapy was defined as first-line; oral dual therapy, as second-line; >2 oral treatments or oral combined with an injectable, as third-line; and injectables only, as fourth-line treatment. Treatment intensification was defined as the start of a higher line of treatment. Comedication, comorbidities, clinical parameters, and other factors associated with treatment choice were identified using multivariate relative risk estimation by Poisson regression with robust error variance.


In the 5-year study period, 485,120 patients (79% of the treated T2DM population) underwent treatment intensification. Changes in treatment choice were clearly visible over the study period, such as a decline in the use of thiazolidinediones (NL, ES, UK) and increases in the use of dipeptidyl peptidase-4 inhibitors (DPP4i) (NL, ES, UK) and glucagon-like peptide-1 receptor agonists (UK). With first-line treatment, advanced age and renal comorbidity were associated with the use of sulfonylureas (SUs; all countries), whereas high body mass index (BMI) was inversely associated with SU use in the United Kingdom and Spain. With second-line treatment, advanced age was associated with metformin + SU use (all countries); and renal comorbidity with SU + DPP4i use in the United Kingdom and the Netherlands. High BMI was associated with metformin + thiazolidinedione (TZD) use in the United Kingdom and Spain, and with metformin + DPP4i in the United Kingdom. With third-line treatment, advanced age and renal comorbidity were associated with the use of SU + insulin (NL, ES, UK). Hemoglobin A1c >8.5% was positively associated, and high BMI was inversely associated, with the use of any third-line combination containing insulin. Across treatment lines TZD and metformin were negatively associated with renal and cardiac morbidity. Second and third line treatment choices strongly depended on prior treatments. With fourth-line treatment, women were more likely to receive glucagon-like peptide-1 receptor agonists than were men in the United Kingdom and Spain.


The results suggest that the main factors driving treatment choice at any stage of intensification were age, hemoglobin A1c, BMI, renal and cardiac morbidity, and treatment history. These drivers were consistent with guidelines on, and contraindications of, specific medications. Differences between countries were generally consistent with, but not solely attributable to, differences in local guidelines and reimbursement policies.


Europe; glucose-lowering drugs; guidelines; treatment choice; type 2 diabetes mellitus

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