Trends in the prescription of antidiabetic medications from 2009 to 2012 in a general practice of...

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Title: Trends in the prescription of antidiabetic medicationsfrom 2009 to 2012 in a ge<!–<query id="Q1">Please checkthe short title that has been created, or suggest an alternative offewer than 80 characters includingspaces.</query>–><!–<RunningTitle>Trends in theprescription of antidiabetic medications from 2009 to 2012 ina ge</RunningTitle>–>neral practice of Southern Italy: Apopulation-based study

Author: Concetta Rafaniello Vincenzo Arcoraci CarmenFerrajolo Liberata Sportiello Maria Giuseppa Sullo FrancescoGiorgianni Gianluca Trifiro Michele Tari Achille P. CaputiFrancesco Rossi Katherine Esposito Dario Giugliano AnnalisaCapuano

PII: S0168-8227(15)00006-6DOI: http://dx.doi.org/doi:10.1016/j.diabres.2014.12.007Reference: DIAB 6245

To appear in: Diabetes Research and Clinical Practice

Received date: 8-5-2014Revised date: 17-10-2014Accepted date: 29-12-2014

Please cite this article as: C. Rafaniello, V. Arcoraci, C. Ferrajolo, L. Sportiello, M.G.Sullo, F. Giorgianni, G. Trifiro, M. Tari, A.P. Caputi, F. Rossi, K. Esposito, D. Giugliano,A. Capuano, Trends in the prescription of antidiabetic medications from 2009 to 2012in a general practice of Southern Italy: A population-based study, Diabetes Researchand Clinical Practice (2015), http://dx.doi.org/10.1016/j.diabres.2014.12.007

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http://dx.doi.org/doi:10.1016/j.diabres.2014.12.007

http://dx.doi.org/10.1016/j.diabres.2014.12.007

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Trends in the prescription of antidiabetic medications from 2009 to 2012 in a general practice 1

of Southern Italy: A population-based study 2

Concetta Rafanielloa, Vincenzo Arcoraci

b, Carmen Ferrajolo

a, Liberata Sportiello

a, Maria Giuseppa 3

Sulloa, Francesco Giorgianni

b, Gianluca Trifirò

b, Michele Tari

c, Achille P. Caputi

b, Francesco 4

Rossia, Katherine Esposito

d, Dario Giugliano

e, Annalisa Capuano

a,*. 5

aRegional Centre of Pharmacosurveillance and Pharmacoepidemiology, Department of 6

Experimental Medicine, Second University of Naples, via de Crecchio 7 - 80138 Naples, Italy 7

bDepartment of Clinical and Experimental Medicine and Pharmacology, Pharmacology Unit, 8

University of Messina, Via Consolare Valeria-Gazzi, 98125 Messina, Italy 9

cCaserta-1 Local Health Service, Caserta, Italy 10

dDepartment of Clinical and Experimental Medicine and Surgery, Second University of Naples, 11

Naples, Italy 12

eDepartment of Medical, Surgical, Neurological, Metabolic Sciences, and Geriatrics, Second 13

University of Naples, Naples, Italy 14

Correspondence: Annalisa Capuano, Regional Centre of Pharmacosurveillance and 15

Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via 16

de Crecchio 7 - 80138 Naples, Italy 17

Tel/FAX +39 081 5667669; email [email protected] 18

Shortened title: Trends in antidiabetic medications 19

2795 words text only; 758 words references; Abstract: 330 words; Figures 2, Tables 3 20

The Authors declare they have no conflict of interest 21

ABSTRACT 22

Objective: To assess the prescribing pattern of antidiabetic drugs (AD) in a general practice of 23

Southern Italy from 2009 to 2012, with focus on behavior prescribing changes. Methods: This 24

retrospective, drug utilization study was conducted using administrative databases of the Local 25

Health Unit of Caserta (Southern Italy) including about 1 million citizens. The standardized 26

prevalence of AD use was calculated within each study year. A sample cohort of 78,789 subjects 27

with at least one prescription of AD was identified during the study period. Results: There was an 28

overall increase of the proportion of the patients treated with monotherapy, which was significant 29

for insulin monotherapy (from 11.2 to 14.6%, p < 0.001). The proportion of patients treated with 30

metformin remained stable (from 68.3% to 67.8%, p = 0.076), while those receiving sulfonylurea 31

dropped from 18.4% to 12.5% (p < 0.001); GLP-1 analogues and DPP-4 inhibitors showed the 32

http://ees.elsevier.com/diab/viewRCResults.aspx?pdf=1&docID=13232&rev=1&fileID=271668&msid=8391D3DF-3B14-4F95-BB8F-BB51CAABBC4C

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greatest increase (from 1.2% to 6.6%, p < 0.001). In the whole sample of 25,148 new AD users, 1

metformin was the most commonly prescribed drug in monotherapy (41.9%), while insulin ranked 2

second (13.3%). Conclusion: This study shows a rising trend of AD monotherapy, with 3

sulfonylureas and incretins showing the more negative and positive trend, respectively. 4

Keywords: Diabetes mellitus, Medical therapy, Prescribing patterns 5

1. Introduction 6

Diabetes is one of the most chronic diseases worldwide, with about 592 million people being 7

affected by 2035 (1). According to the World Health Organization (WHO), diabetes will represent 8

the 7th leading cause of death in 2030, with an estimated prevalence of 7.8% (2). A steadily 9

increase of diabetes prevalence has also been registered in Italy (3), from 3.9% in 2001 to 5.0% in 10

2012. The two main forms of diabetes are type 1 diabetes, characterized by deficient insulin 11

production, and type 2 diabetes, characterized by a mixture of insulin resistance and insulin 12

deficiency; over 90% of cases are represented by type 2 diabetes (4). The global rising of obesity 13

and sedentary lifestyle represent hard risk factors for type 2 diabetes. Diet, exercise and drugs are 14

the mainstay of diabetes management (5-8). In the last decade, the available pharmacological 15

options have expanded with the introduction of new antidiabetic drugs (ADs), such as the glucagon-16

like peptide-1 (GLP-1) analogues and the dipeptidyl peptidase-4 (DPP-4) inhibitors. The rising of 17

diabetes prevalence and the availability of these new drugs represent the main cause of the 18

increased ADs utilization and related costs worldwide. To date, several studies have analysed the 19

trend in the use of ADs, which indicated an increased trend in consumption of these drugs over 20

time, with sharp differences between and within countries (9-19). In Italy, data on drugs 21

consumption in 2012 showed that drugs in the ATC group A “alimentary tract and metabolism”, 22

which includes ADs, were those with an higher increase in expenditure (+22.5%) and consumption 23

(+7.8%) compared with data of 2011 (20). A picture of ADs prescription data in Italy is only 24

available from some Northern Italian Counties, and is consistent with other worldwide scientific 25

evidence (18,19). Within this scenario, and in light of the recent introduction on the market of new 26

ADs, the aim of this study was to assess the prescribing pattern of ADs in a general practice of 27

Southern Italy, with focus on behaviour prescribing changes. 28

2. Materials and methods 29

This retrospective, drug utilization study was conducted using administrative databases of the Local 30

Health Unit (LHU) of Caserta from Campania region (Southern Italy). The source population 31

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included about 1 million citizens living in the catchment area of Caserta. The database collects 1

anonymized claims data about: a) drugs routinely dispensed to the patients and reimbursed by the 2

Italian National Health System, prescribed by either general practitioners (GP) or specialists 3

working in both public and private sector; b) drugs directly supplied to patients by LHU (Direct 4

Distribution, DD), or by hospitals through local pharmacies (DPC), both at enrolment and during 5

the follow-up period. Dispensing data contained information about unique patient identifier, 6

patients‟ demographics, branded and generic drug name and related Anatomical Therapeutic 7

Chemical (ATC) classification code, quantity and dispensing date. These databases were linked 8

anonymously using encrypted patient codes according to the Italian law for confidentiality data. No 9

ethical approval is required for using encrypted retrospective information. Since type 1 and type 2 10

diabetes could not be accurately distinguished from the available data, the type of diabetes was not 11

considered in this analysis. 12

2.1 Study population 13

From the source population, we identified all the subjects with at least one AD prescription during 14

the study period January 1st, 2009 –December 31st, 2012. Moreover, according to the inclusion 15

criteria, patients had to be alive, registered in the list of LHU for two years, during which they had 16

to receive drug prescription reimbursed by the Italian National Health System, until the date of AD 17

prescription. No age restriction was applied. The drug exposure under study included all ADs 18

(ATC: A10*). According to their first prescription during the enrolment period, patients were 19

stratified in two main categories :a) monotherapy; and b) polytherapy and each of them into two 20

sub-categories. Patients with a first prescription of only one drug belonging to the biguanides 21

(A10BA), sulfonamides, urea derivatives (A10BB), α-glucosidase inhibitors (A10BF), 22

thiazolidinediones (A10BG), dipeptidyl peptidase-4 inhibitors (A10BH) and others blood glucose 23

lowering drugs (A10BX), were included in the monotherapy AD. Patients with the first prescription 24

of only one of the insulin group (Human: A10AB01, A10AC01, A10AD01 and Analogues: 25

A10AB04, A10AB05, A10AB06, A10AC04, A10AD04, A10AE04, A10AE05 or A10AD05) were 26

included in the insulin monotherapy group. The polytherapy group was distinguished as fixed 27

combination group, that was made up of patients with prescription of drugs in the ATC A10BD 28

(combinations of oral blood glucose-lowering drugs), and no-fixed combination group, composed 29

of subjects with an overlapping period from the first and second prescription of oral AD of at least 30

of 15 days. This definition is consistent with the indications reported in previous studies (21,22). 31

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2.2 Statistical analysis 1

One-year prevalence of AD treatment was evaluated, for each year, as the ratio between the number 2

of patients who received at least one AD prescription during the observational year and the number 3

of all resident subjects alive in the same period. Yearly incidence of AD treatment was assessed as 4

the number of new AD users per year divided by the number of residents at risk of receiving an AD 5

prescription (i.e. alive residents during the observation year minus prevalent AD user at the end of 6

the previous years). New users were identified as patients receiving at least one AD prescription 7

during the observational year, without any recorded AD prescription in the previous year. Both 8

prevalence and incidence of use were expressed as rates per 1000 inhabitants together with 95% 9

confidence interval (CI). Frequency analyses by age-category over the study period were also 10

conducted. The incidence of AD treatment was also stratified by drug class for each study year. The 11

Cochrane-Armitage test was used to assess the statistical significance of patients‟ characteristics 12

and prescribing patterns from 2010 to 2012. Significance was set at a level of P < 0.05. Statistical 13

analyses were performed using STATA vs 11.1 (STATA Corporation, Texas, USA). 14

15

3. Results 16

A sample cohort of 78,789 subjects with at least one prescription of AD was identified during the 17

study period. Overall cumulative prevalence of AD use in the Caserta LHU remained stable from 18

62.6 (95% CI: 62.1 to 63.1)/1000 inhabitants in 2009, to 62.3 (95% CI: 61.8- 62.8)/1000 inhabitants 19

in 2012. Prevalence increased with age with a peak in 65-74 years group (Figure 1). Overall 20

cumulative incidence of antidiabetic drug use per 1000 inhabitants decreased from 11.2 (95% CI 21

11.0-11.4) in 2010, to 7.4 (95%CI 1.2-7.6) in 2012 (Figure 2). When stratified by age category, the 22

peak of incidence was observed in people 65-74 years old both in 2010 and 2012, and in subjects 23

over 74 in 2011. 24

3.1 AD prescription in newly-treated patients 25

From 2010 to 2012, we observed a progressive decrease of the absolute number of new users of 26

ADs over the study years, from 9,852 in the 2010, 9,509 in the 2011, to 6,325 patients in the 2012, 27

associated with a change in the prescribing pattern of first-line therapy (Table 1). There was an 28

overall increase of the proportion of the patients treated with monotherapy from 2010 to 2012, 29

specifically from 60.1% (N 5,919) to 62.1% (N 3,929) for monotherapy AD (P=0.212), and from 30

11.2% (N 1,104) and 14.6% (N 924) for insulin monotherapy (P<0.001); this was associated with 31

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an overall decrease of polytherapy, including both fixed and no-fixed combinations (from 19.7% to 1

16.4%, and from 9.10% to 6.8%, respectively, P<0.001 for both). As specific drug monotherapy is 2

concerned (Table 2), the proportion of newly treated patients with metformin (the only available 3

biguanide on the Italian market) remained stable across the years of observation (from 68.3% in 4

2010 to 67.8% in 2012, P = 0.951), while the percentage of new patients treated whit a sulfonylurea 5

dropped steadily, from 18.4% in 2010 to 12.5% in 2012 (P < 0.001). While GLP-1 analogues and 6

DPP-4 inhibitors, showed the greatest relative increase during the study period (from 1.2% to 6.6%, 7

P < 0.001), the use of other AD, showed small differences. In particular, a small but statistically 8

significant increase of new acarbose users (from 4.9% in the 2010 to 5.9% in the 2012; P = 0.045) 9

and a not significant increase in new glinides users were detected (from 6.1% in the 2010 to 6.3% in 10

the 2012; P = 0.0881). On the contrary, a small but significant reduction of new pioglitazone users 11

was highlighted, in particular from 1.1% in the 2010 to 0.9 in the 2012. The percentage of patients 12

starting treatment with insulin analogues rose from 84.0% in 2010 to 92.4% in 2012 (P < 0.001), 13

according to a decrease of human insulin use (from 16.0% to 7.6%, P < 0.001). 14

3.2 Demographic characteristics of AD new users 15

Table 3 reports the demographic and clinical characteristics (gender, mean age, and age strata), 16

stratified by drug, for all patients with at least one prescription of AD any time across the study 17

period (N=25,148). Metformin was the most commonly prescribed drug (41.9%), without 18

difference in gender; the mean age of metformin new users was 60.1 ± 15.3 years, with a peak 19

(45.7%) in the age stratum of 45-64 years. Classic insulin secretagogues, including sulfonylureas 20

and glinides, ranked second (9.7%) and third (3.8%), respectively, among monotherapy AD group: 21

the age of sulfonylureas and glinides users was above the mean age of the whole population, and in 22

absolute the mean age of glinides users was the highest (65.6 ± 17.5 years, P = 0.01). A high 23

percentage of patients aged >74 years took glinides (33.4%) or a sulfonylurea (27.4%). Among the 24

other noninsulin drugs, acarbose, incretins (GLP-1 analogues and DPP-4 inhibitors) and 25

pioglitazone ranked fourth, fifth and sixth, respectively, with a total percentage of noninsulin 26

monotherapy prescriptions of 6.3%. The mean age of new incretins users in monotherapy was the 27

lowest (57.1 ± 17.2 years), according to the lowest percentage of patients over 74 (11.8%). Insulin 28

ranked second among the antidiabetic drugs given in monotherapy, with a total of 13.3% new users, 29

the most treated with insulin analogues. The most new human-insulin users were over 74 (35.6%) 30

while new treatments with insulin analogues are mostly prescribed between 45 and 65 years 31

(30.4%). Polytherapy, in terms of both fixed and no fixed combinations, were used by one fourth 32

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(25.1%) of the whole new users, with most using fixed combination therapy (17.2%): the age peak 1

of polytherapies occurred between 45-64 years for both (fixed and no fixed). 2

4. Discussion 3

This study, based on administrative databases of the Local Health Unit (LHU) of Caserta, showed 4

that the prevalence of patients on AD treatment remained stable across the study period (around 62 5

per 1000 inhabitants in the years 2009-2012 ) with a peak in subjects aged 65-74 years. With regard 6

to the distribution of new users of AD treatment per year, a rising trend of monotherapy (both AD 7

and insulin), and a steady decrease of polytherapy, both fixed and no-fixed combinations were 8

detected. In particular, metformin, as monotherapy treatment, was the oral AD mostly used as 9

starting therapy during the whole study period; sulfonylureas and incretins showed the more 10

negative and positive trend, respectively, across the years. These findings are consistent with the 11

more recent American guidelines, according to metformin as monotherapy intervention represents 12

the first choice at the early stage of the disease (5). In apparent contrast to that reported in other 13

Italian studies (18,19), our results do not show a steady increase in the use of metformin as initial 14

therapy in new users: this likely could reflect the introduction of the regional legislative decree n.51 15

on September 2010, as a measure of regional pharmaceutical expenditure containment, which 16

established a form of patient co-payment for some drugs off-patent, such as metformin. Given the 17

low absolute cost of metformin, this would have result in more diabetic people buying metformin 18

without the prescription of the general practitioner, thus escaping the database. Moreover, another 19

conceivable explanation for our results, different to the other ones reported, could also be the 20

different time frame analysis among the studies. At the same time, the number of patients with 21

diabetes treated with combinations of oral antidiabetic drugs decreased, suggesting that the 22

availability on the market of new classes of drugs, such as incretins, has expanded the possibility of 23

“personalizing” therapy in order to achieve better glucose control. With regard to insulin 24

monotherapy, our analysis revealed also a rising use in new users (from 11.2 in 2010 to 14.6 in 25

2012). These data could reflect either a more severe hyperglycemia or a renal impairment status that 26

represents one of the contraindications of biguanides or sulfonylureas use (18, 23). The present 27

study also assessed associations between patient characteristics and the prescribing pattern of 28

differential antidiabetic drugs. While no gender effect was evident from the analysis of prescribing 29

patterns, age seem to influence the choice of antidiabetic drugs in new users. For instance, glinides 30

and incretins were the drugs associated with the higher and lower mean age at starting therapy, 31

respectively, with a difference of 7.5 years between the groups. Older individuals with type 2 32

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diabetes are inherently at higher risk of serious complications brought on by hypoglycemia, in part 1

because of the presence of age-related comorbid conditions and also because their symptoms are 2

often misinterpreted and not treated as quickly and effectively as needed (24). Accordingly, the 3

DPP-4 inhibitor alogliptin has been shown to be efficacious and safe, without increased incidence 4

of hypoglycemia or weight gain in post hoc analyses of subpopulations of older patients with type 2 5

diabetes mellitus (aged 65–80 years), as monotherapy and in combination with other antidabetic 6

drugs (25). The theoretical advantages of DPP-4 inhibitors in older patients are not reflected by the 7

prescribing patterns, especially in the age stratum >74 years, where the use of incretins dropped to 8

11.8%, as compared with 33.4% of glinides. In particular, considering insulin secretagogues, 9

patients over 74 represent 29,1% of glinides/sulfonylureas new users, although these drugs are not 10

recommended in older people. The underutilization of DPP-4 inhibitors could reflect physician's 11

caution in prescribing the newer classes of glucose-lowering drugs in the elderly population, 12

although the comforting safety data (25). However, although the new oral antidiabetic drugs appear 13

to have a lower risk of hypoglycemia, making them theoretically attractive for older patients, their 14

efficacy and safety profile need to be further investigated in long-term studies with appropriate 15

comparators on the clinical endpoint. Our results show that the use of metformin as monotherapy is 16

higher in the age-stratum 45-64 years. In agreement with previous data (18), younger patients were 17

more likely to be prescribed metformin, as its use was low in older patients, probably owing to renal 18

contraindications. We also reported an overall decrease of the incidence of new users of antidiabetic 19

drugs, in contrast with national and international data that predicted an increase of the incidence of 20

antidiabetic drugs use. However, the administrative databases of Local Health Unit are not able to 21

capture the potential effect of the policy/economic intervention by the National Health System, 22

especially of those patients with diabetes who decide to bypass prescriptions, owned by co-23

payment, and buy directly low-cost drugs, as metformin and sulfonylureas. This limitation could 24

also explain the difference between the total number of yearly new users and the number of anytime 25

new users (25,686 and 25,148 respectively). Several limitations of our study should be recognized. 26

First of all, it is well known that administrative health database, useful tools in observational drug 27

utilization studies are characterized by several limitations such as the absence of important clinical 28

information which limits interpretation of data. Second, the use of outpatient dispending data does 29

not inform whether antidiabetic medications were actually taken by the patients; although these data 30

are ideal for measuring prescription patterns, non-adherence to treatment is not captured. Third, in 31

the absence of a clinical diagnosis of diabetes (type 1 or type 2), we decided to describe prescribing 32

trends on the overall population with diabetes since differentiation between these main forms of 33

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diabetes based on patients‟ age and use of insulin are imperfect (10). However, more than 90% is 1

estimated to be type 2 diabetes. On the other hand, this study has also strengths; in particular, the 2

use of linked administrative databases for identifying all patients treated with antidiabetic drugs 3

across 3 consecutive years makes it possible to follow actual changes in drug prescriptions. 4

5. Conclusions 5

The results of our study show that the prevalence of patients on AD treatment remained stable 6

across the study period (2009-2012), with a peak in subjects aged 65-74 years. Moreover, data also 7

show a rising trend of monotherapy, and a steady decrease of polytherapy, both fixed and no-fixed 8

combinations; metformin, as monotherapy treatment, was the oral AD with the higher proportion 9

during the entire study period; sulfonylureas and incretins showed the more negative and positive 10

trend, respectively, across the years. The changes in antidiabetic drugs prescription patterns 11

probably reflect the impact of recent guidelines of diabetes treatment, the introduction of different 12

classes of medications to the marketplace, and the potential effect of the policy/economic 13

intervention by the local National Health System. 14

Conflict of interest 15

The authors declare that they have no conflict of interest with the article. 16

References 17

1. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of 18

diabetes prevalence in adults for 2013 and projections for 2035. Diabetes Res Clin Pract 2014. 103 (2): 137-19

149 20

2. Global status report on non communicable diseases 2010. Geneva, World Health Organization, 2011. 21

3. Italian national institute of statistics http://www3.istat.it/dati/catalogo/20121218_00/ 22

4. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and 23

classification of diabetes mellitus. Geneva, World Health Organization, 1999 (WHO/NCD/NCS/99.2) 24

5. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care 2014;37 25

(Suppl 1):S14-S80. 26

6. Morgillo F, Sasso FC, Della Corte CM, Festino L, Manzo A, Martinelli E, et al. Metformin in lung cancer: 27

rationale for a combination therapy. Expert Opin Investig Drugs 2013;33:1401-9. 28

7. Esposito K, Chiodini P, Capuano A, Petrizzo M, Improta MR, Giugliano D. Basal supplementation of 29

insulin lispro protamine suspension versus insulin glargine and detemir for type 2 diabetes: meta-analysis of 30

randomized controlled trials. Diabetes Care 2012;35:2698-705. 31

of 15

Accep

ted

Man

uscr

ipt

9

8. Esposito K, Capuano A, Giugliano D. Humalog (lispro) for type 2 diabetes. Expert Opin Biol Ther 1

2012;12:1541-50. 2

9. Kohro T, Yamazaki T, Sato H, Harada K, Ohe K, Komuro I, et al. Trends in antidiabetic prescription 3

patterns in Japan from 2005 to 2011. Int Heart J 2013;54:93-7. 4

10. Cohen FJ, Neslusan CA, Conklin JE, Song X. Recent antihyperglycemic prescribing trends for US 5

privately insured patients with type 2 diabetes. Diabetes Care 2003;26:1847-51. 6

11. Wysowski DK, Armstrong G, Governale L. Rapid increase in the use of oral antidiabetic drugs in the 7

United States, 1990-2001. Diabetes Care. 2003;26(6):1852-1855. 8

12. Alexander GC, Sehgal NL, Moloney RM, Stafford RS. National trends in treatment of type 2 diabetes 9

mellitus, 1994-2007. Arch Intern Med 2008;168:2088-94. 10

13. Mann DM, Woodward M, Ye F, Krousel-Wood M, Muntner P. Trends in medication use among US 11

adults with diabetes mellitus: glycemic control at the expense of controlling cardiovascular risk factors. Arch 12

Intern Med 2009;169:1718-20. 13

14. Walley T, Hughes D, Kendall H. Trends and influences on use of antidiabetic drugs in England, 1992-14

2003. Pharmacoepidemiol Drug Saf 2005;14:769-73. 15

15. Melander A, Folino-Gallo P, Walley T, Schwabe U, Groop PH, Klaukka T, et al. Utilisation of 16

antihyperglycaemic drugs in ten European countries: different developments and different levels. 17

Diabetologia 2006;49:2024-9. 18

16. Lub R, Denig P, van den Berg PB, Hoogenberg K, de Jong-van den Berg LT. The impact of new insights 19

and revised practice guidelines on prescribing drugs in the treatment of Type 2 diabetes mellitus. Br J Clin 20

Pharmacol 2006;62:660-5. 21

17. Filion KB, Joseph L, Boivin JF, Suissa S, Brophy JM. Trends in the prescription of anti-diabetic 22

medications in the United Kingdom: a population-based analysis. Pharmacoepidemiol Drug Saf 23

2009;18:973-6. 24

18. Mazzaglia G, Yurgin N, Boye KS, Trifirò G, Cottrell S, Allen E, et al. Prevalence and antihyperglycemic 25

prescribing trends for patients with type 2 diabetes in Italy: a 4-year retrospective study from national 26

primary care data. Pharmacol Res 2008;57:358-63. 27

19. Baviera M, Monesi L, Marzona I, Avanzini F, Monesi G, Nobili A, et al. Trends in drug prescriptions to 28

diabetic patients from 2000 to 2008 in Italy's Lombardy Region: a large population-based study. Diabetes 29

Res Clin Pract 2011;93:123-30. 30

20. Osservatorio Nazionale sull‟Impiego dei Medicinali - L‟uso dei farmaci in Italia gennaio - settembre 31

2012 (National Monitoring Center for Drug Use. The Use of Drug in Italy. Rome, National Ministry of 32

Health). 33

21. Colombo GL, Rossi E, De Rosa M, Benedetto D, Gaddi AV. Antidiabetic therapy in real practice: 34

indicators for adherence and treatment cost. Patient Prefer Adherence 2012;6:653-61. 35

of 15

Accep

ted

Man

uscr

ipt

10

22. Cheong C, Barner JC, Lawson KA, Johnsrud MT. Patient adherence and reimbursement amount for 1

antidiabetic fixed-dose combination products compared with dual therapy among Texas Medicaid recipients. 2

Clin Ther 2008;30:1893-907. 3

23. Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control 4

and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term 5

intensive insulin therapy. Diabetes Care 2008;31:1927-32. 6

24. Zamitt NN, Frier BM. Hypoglycemia in type 2 diabetes. Diabetes Care 2005; 28: 2948–61. 7

25. Pratley RE, McCall T, Fleck PR, Wilson CA, Mekki Q. Alogliptin use in elderly people: a pooled 8

analysis from phase 2 and 3 studies. J Am Geriatr Soc 2009; 57: 2011–9. 9

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Table 1. New users of antidiabetic drugs per calendar year and group of therapy.

Year (number of patients,

%)

2010 (9,852, %) 2011 (9,509, %) 2012 (6,325, %) P value

Monotherapy AD 5,919 (60.1) 5,750 (60.5) 3,929 (62.1) 0.212

Monotherapy Insulin 1,104 (11.2) 1,330 (14.0) 924 (14.6) <0.001

Fixed-combination 1,937 (19.7) 1,678 (17.6) 1,040 (16.4) <0.001

No fixed-combination 892 (9.1) 751 (7.9) 432 (6.8) <0.001

Table

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Table 2. New users of monotherapy antidiabetic drugs per calendar year and drug.

Year (number of patients) 2010 (N. 7,023) 2011 (N. 7,080) 2012 (N. 4,853) P value

Monotherapy AD Metformin 4,043 (68.3) 3,895 (67.7) 2,662 (67.8) 0.951

Sulfonylureas 1,090 (18.4) 882 (15.3) 492 (12.5) <0.001

Glinides 359 (6.1) 350 (6.1) 248 (6.3) 0.0881

Acarbose 290 (4.9) 271 (4.7) 230 (5.9) 0.045

GLP-1 analogues and

DDP4-inhibitors 72 (1.2) 264 (4.6) 260 (6.6)

<0.001

Thiazolidinediones 65 (1.1) 88 (1.5) 37 (0.9) 0.022

Sub total 5,919 (100) 5,750 (100) 3,929 (100)

Monotherapy Insulin Analogues 927 (84.0) 1,168 (87.8) 854 (92.4) <0.001

Human 177 (16.0) 162 (12.2) 70 (7.6) <0.001

Sub total 1,104 (100) 1,330 (100) 924 (100)

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Table 3. Distribution of clinical characteristics of new users* of antidiabetic drugs anytime by drug.

Total Monotherapy AD Monotherapy Insulin Polytherapy

Number (%) Metformin Sulfonylureas Glinides Acarbose Incretins Thiazolidine

diones

Human Analogues Fixed

combination

No fixed

combination

25,148 (%) 10,531 (%) 2,434 (%) 952 (%) 789 (%) 595 (%) 189 (%) 405 (%) 2,939 (%) 4,323 (%) 1,991 (%)

Gender (p=0.296)

Female 12,779 (50.8) 5,312 (50.4) 1,249 (51.3) 492 (51.7) 412 (52.2) 294 (49.4) 95 (50.3) 215 (53.1) 1,536 (52.3) 2,212 (51.2) 962 (48.3)

Male 12,369 (49.2) 5,219 (49.6) 1,185 (48.7) 460 (48.3) 377 (47.8) 301 (50.6) 94 (49.7) 190 (46.9) 1,403 (47.7) 2,111 (48.8) 1,029 (51.7)

Mean Age

(±SD)

61.1 (17.1) 60.1 (15.3) 64.1 (16.1) 65.6 (17.5) 63.5 (14.6) 57.1 (17.2) 57.5 (20.0) 64.4 (20.7) 59.6 (20.7) 62.7 (17.9) 59.1 (17.9)

Age group (years) (p<0.001)

≤14 526 (2.1) 106 (1.0) 37 (1.5) 21 (2.2) 8 (1.0) 20 (3.4) 9 (4.8) 19 (4.7) 127 (4.3) 110 (2.5) 69 (3.5)

15-44 2,973 (11.8) 1,298 (12.3) 207 (8.5) 74 (7.8) 60 (7.6) 85 (14.3) 31 (16.4) 34 (8.4) 487 (16.6) 432 (10.0) 265 (13.3)

45-64 10,079 (40.1) 4,816 (45.7) 883 (36.3) 291 (30.6) 297 (37.6) 288 (48.4) 66 (34.9) 115 (28.4) 894 (30.4) 1,589 (36.8) 840 (42.2)

65-74 6,178 (24.6) 2,613 (24.8) 639 (26.3) 248 (26.1) 262 (33.2) 132 (22.2) 54 (28.6) 93 (23.0) 674 (22.9) 1,034 (23.9) 429 (21.5)

>74 5,392 (21.4) 1,698 (16.1) 668 (27.4) 318 (33.4) 162 (20.5) 70 (11.8) 29 (15.3) 144 (35.6) 757 (25.8) 1,158 (26.8) 388 (19.5)

* Patients with at least one prescription of AD any time across the study period were included in the table.

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2009 2010 2011 20120-14 1.7 2 2.6 2.515-44 8.1 9 10 9.845-64 94.6 97.3 100 99.665-74 232.4 232.9 227.4 218.3>74 229.1 206.4 193.2 172.9

0 0 0 0tot 62.6 63.1 63.7 62.395%(‐) 0.5 0.5 0.5 0.595%(+) 0.5 0.5 0.5 0.5

0

50

100

150

200

250

2009 2010 2011 2012Ye

arly cum

ulative prevalen

ce

Figure 1. Yearly prevalence of antidiabetic drug users per 1,000 inhabitants stratified by age‐category (yrs).

0‐14 15‐44 45‐64 65‐74 >74 tot

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fascia 2010 2011 2012<14 yrs 0.9 1.5 1.115‐44 yrs 2.7 3.1 2.2 fascia <14 yrs 15‐44 yrs 45‐64 yrs 65‐74 yrs >74 yrs totale 95%(‐) 95%(+)45‐64 yrs 18.7 17.8 11.8 anno 2010 0.9 2.7 18.7 41.8 41.1 11.2 0.2 0.265‐74 yrs 41.8 40.5 25.9 anno 2011 1.5 3.1 17.8 40.5 41.9 11.2 0.2 0.2>74 yrs 41.1 41.9 24.7 anno 2012 1.1 2.2 11.8 25.9 24.7 7.4 6.2 0.2

totale 11.2 11.2 7.4

0

5

10

15

20

25

30

35

40

45

50

2010 2011 2012

Yearly in

cide

nce pe

r 1,000

inha

bitants

Figure 2. Yearly incidence of antidiebetic drug users per 1,000 inhabitants stratified by age‐category (yrs)

<14 yrs 15‐44 yrs 45‐64 yrs 65‐74 yrs >74 yrs totale

Trends in the prescription of antidiabetic medications from 2009 to 2012 in a general practice of...

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