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Use of Exenatide and Liraglutide in Denmark: a Drug Utilization Study

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Use of Exenatide and Liraglutide in Denmark: a Drug Utilization Study Eur J Clin Pharmacol DOI 10.1007/s00228-013-1595-4 PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Use of exenatide and liraglutide in Denmark: a drug utilization study Anton Pottegård & Bine Kjøller Bjerregaard & Michael Due Larsen & Kasper Søltoft Larsen & Jesper Hallas & Filip K. Knop & Søren Ilsøe Moreno Received: 10 June 2013 /Accepted: 23 September 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract was most often performed by a hospital physician and was not Purpose The purpose of this study was to characterise the associated with any changes in concomitant treatment with utilization of the glucagon-like peptide-1 (GLP-1) analogues antihypertensives, cholesterol-lowering drugs or exenatide and liraglutide in Denmark. anticoagulants. Of liraglutide and exenatide users, 38 % and Methods From the Danish National Prescription Registry, we 43 % also used insulin. Low kidney function (eGFR<30 ml/ extracted all prescriptions for either liraglutide or exenatide min) was found in 10.1 % and 9.0 % of users of liraglutide and twice-daily in the period 1 April 2007 to 31 December 2012. exenatide respectively. Using descriptive statistics, we calculated incidence rates, Conclusions The preferred GLP-1 analogue in Denmark is prevalence proportions, daily consumption, and concomitant liraglutide. Certain aspects of the utilization of GLP-1 drug use. For a subset of users we included data from other analogues, such as large regional differences and concomitant registries and characterised the baseline characteristics of use of GLP-1 analogues and insulin, warrant further incident users of GLP-1 analogues. investigation. Results We identified 21,561 and 2,354 users of liraglutide and exenatide respectively. From market entry in 2009 Keywords GLP-1 . Diabetes mellitus . Denmark . liraglutide showed an increasing prevalence reaching 2.4 per Prescribing . Drug utilization thousand inhabitants in 2012. Exenatide ranged between 0.01 and 0.25 per thousand inhabitants from 2007 to 2012. Treatment intensity showed geographical variation ranging Introduction from 1.84per thousand inhabitants to 3.22 per thousand inhabitants for liraglutide. Average doses were 1.34 mg/day More than 200,000 Danes are estimated to suffer from type 2 (liraglutide) and 16.4 μg/day (exenatide). Treatment initiation diabetes [1–3]. The disease and related complications such as ischaemic heart disease, peripheral neuropathy and related A. Pottegård (*) : M. D. Larsen : K. S. Larsen : J. Hallas micro- and macrovascular complications constitute a Institute of Public Health, Clinical Pharmacology, University of worldwide increasing threat to public health and a massive Southern Denmark, JB Winsløwsvej 19, 2, 5000 Odense C, Denmark economic burden to society [1, 4]. Metformin in combination e-mail: [email protected] with lifestyle changes is the first drug of choice to achieve B. K. Bjerregaard glycaemic control [5, 6]. This is based on evidence of Data Deliveries and Medicinal Products Statistics, Sector for clinically relevant effects on glucose levels, micro- and National Health Surveillance and Research, Statens Serum Institut, macrovascular outcome measures, and mortality [7–10]. 2300 København S, Denmark However, sufficient glycaemic control is often not maintained F. K. Knop using metformin combined with lifestyle changes alone, and Diabetes Research Division, Department of Medicine, additional antidiabetic drugs are needed to achieve glycaemic Gentofte Hospital, 2900 Hellerup, Denmark goals. Current treatment guidelines suggest the use of dipeptidyl peptidase 4 (DPP-4) inhibitors, sulphonylureas, S. I. Moreno Institute for Rational Pharmacotherapy, Danish Health and thiazolidinediones, basal insulins or glucagon-like peptide 1 Medicines Authority, 2300 København S, Denmark (GLP-1) analogues as second-line add-on treatment. Of these, Eur J Clin Pharmacol GLP-1 analogues have gained increased interest owing to Exenatide twice-daily and once-weekly were marketed in glucose-lowering properties comparable to sulphonylureas Denmark in April 2007 and October 2011 respectively, and and superior to DPP-4 inhibitors and thiazolidinedione as liraglutide in July 2009. We thus obtained data regarding these add-ons to metformin, a low risk of hypoglycaemia, and their drugs from 1 April 2007 to 31 December 2012. body weight-reducing effect [11–14]. GLP-1 analogues stimulate insulin secretion and inhibit glucagon secretion in Databases a glucose-dependent manner [15]. Furthermore, GLP-1 analogues reduce gastric emptying, appetite and food intake, The Danish National Prescription Registry (DNPR) [19] and, consequently, give rise to weight loss [15]. Thus, GLP-1 contains data on all prescription drugs redeemed by Danish analogues are considered particularly relevant when weight citizens (population 5.5 million) since 1995. Prescription data reduction is central to treatment. Thereby, GLP-1 analogues include the type of drug, date of dispensing, and quantity. can be considered in a substantial proportion of overweight Dosing information and indication for each prescription are patients with insufficient glycaemic control on metformin available in the DNPR, but data are incomplete and are treatment [16]. therefore not used in the present study. Drugs are categorized At present, three GLP-1 analogues are available: exenatide according to the Anatomic Therapeutic Chemical (ATC) in a formulation administered twice-daily (Byetta™), classification; a hierarchical classification system developed liraglutide (Victoza™) administered once-daily, exenatide in by the World Health Organisation (WHO) for the purposes of a formulation designed for once-weekly administration drug use statistics [20], and the quantity dispensed for each (Bydureon™), and the most recent lixisenatide (Lyxumia™), prescription is expressed by the defined daily dose (DDD) administered once-daily. They were introduced in Europe in measure, also developed by the WHO [20]. 2007, 2009, 2011 and 2013 respectively. As current treatment Odense University Pharmacoepidemiological Database guidelines recommend the use of these drugs in different (OPED) is a regional prescription database covering Funen dosages and in a variety of combinations with other County (population 480,000) since 1990, extended to the antidiabetic drugs, while also advocating individualised, region of Southern Denmark (1.2 million) in 2007 [21]. The patient-centred treatment regimens, there is a strong need to structure of the database is roughly similar to that of the have post-marketing knowledge of the use patterns, actual national database. However, contrary to the national database, concordance with treatment guidelines and characteristics of prescription drugs that are not reimbursed (i.e. oral the GLP-1 analogue drug users. Unfortunately, data on the contraceptives, hypnotics, sedatives, dieting products and utilization of GLP-1 analogues in Denmark are sparse. The certain antibiotics) are not covered. nationwide prescription registry available in Denmark offers a Funen County Patient Administrative System (FPAS) unique tool for pharmacoepidemiological research [17, 18]. holds data on all hospital contacts and discharge diagnoses Accordingly, the aim of the present study was to characterise for the population of Funen since 1977 for inpatients and since the utilization of GLP-1 analogues in Denmark from a 1989 for outpatients. The diagnoses have been encoded national perspective, using population-based pharmacy according to the International Classification of Diseases 10th dispensing data. We also compared the characteristics of revision (ICD-10) since January 1994. actual GLP-1 analogue users with characteristics of patients The laboratory database of Odense University Hospital enrolled in the core clinical trials of GLP-1 analogues. (NetLab) is a clinical laboratory system, which holds information on all blood samples analysed at various hospital laboratories in the Funen area since November 1999. The Material and methods coverage includes both primary and secondary health providers as well as inpatients and outpatients. In this study, we described the use of the GLP-1 analogues Linkage was performed using a unique personal identifier, liraglutide and exenatide (twice-daily) in Denmark, using the Danish Central Person Registry Code, which is assigned to descriptive statistics. The analysis was divided into five all Danish citizens since 1968 [22]. questions, four of which were answered using national data and one was answered using data from the geographical Study drugs region of Southern Denmark. Data were extracted from the Danish National Prescription We included all prescriptions for exenatide twice-daily and Registry. For the comparison of real-life users and trial liraglutide. Exenatide twice-daily has the ATC code enrolees, we also extracted data from the following regional A10BX04 and a DDD of 15 μg. Liraglutide has the ATC databases: The Odense University Pharmacoepidemiological code A10BX07 and a DDD of 1.2 mg. Database, the Funen County Patient Administrative System We excluded prescriptions for exenatide in its once-weekly and the laboratory database of Odense University Hospital. formulation, as it was introduced late in the study period and Eur J Clin Pharmacol was rarely used (234 unique subjects within the study Which drugs relevant to the treatment of type 2 diabetes period). Lixisenatide was not included at it was marketed are used by users of GLP-1 analogues? in Denmark after the study period had ended (15 April 2013). To
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