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`Diabetes Care Volume 37, May 2014
`
`se of Antidiabetic Drugs in the
`
`U.S., 2003—2012
`Diabetes Care 2014;37:1367—1374 I DO]: 10.2337/dc13-2289
`
`OBJECTIVE
`
`To describe market trends for antidiabetic drugs, focusing on newly approved
`drugs, concomitant use of antidiabetic drugs, and effects of safety concerns and
`access restrictions on thiazolidinedione use.
`
`RESEARCH DESIGN AND MEI'HODS
`
`Nationally projected data on antidiabetic prescriptions for adults dispensed from
`U.S. retail pharmacies were extracted from IMS Health Vector One National and
`Total Patient Tracker for 2003-2012 and from Encuity Research Treatment
`Answers and Symphony Health Solutions PHAST Prescription Monthly for 2012.
`
`RESULTS
`
`Since 2003, the number of adult antidiabetic drug users increased by 42.9% to 18.8
`million in 2012. Metforrnin use increased by 97.0% to 60.4 million prescriptions
`dispensed in retail pharmacies in 2012. Among antidiabetic drugs newly approved
`for marketing between 2003 and 2012, the dipeptidyl peptidase-4 (DPP-4) in-
`hibitor sitagliptin had the largest share with 10.5 million prescriptions in 2012.
`Rosiglitazone use plummeted to <13,000 prescriptions dispensed in retail or
`mail-order pharmacies in 2012. Concomitancy analyses showed that 44.9% of
`metformin use was for monotherapy. Between 33.4 and 48.1% of sulfonylurea,
`DPP-4 inhibitor, thiazolidinedione, and glucagon-like peptide 1 analog use was not
`accompanied by metformin.
`
`CONCLUSIONS
`
`The antidiabetic drug market is characterized by steady increases in volume, and
`newly approved drugs experienced substantial uptake, especially DPP-4 inhibi-
`tors. The use of rosiglitazone has been negligible since restrictions were put in
`place in 2011. Further study is needed to understand why one-third to one-half of
`other noninsulin antidiabetic drug use was not concomitant with metformin use
`despite guidelines recommending that metformin be continued when other
`agents are added to treatment.
`
`In 2010, 18.8 million adults in the U.S. had been diagnosed with diabetes mellitus,
`7.0 million additional Americans were affected by undiagnosed diabetes, and an
`estimated 1.9 million adults received a new diagnosis of diabetes during that year
`(1). The number of Americans with diabetes who have or have not received a di-
`agnosis is expected to increase to 44.1 million in 2034 (2). In 2012, the total cost of
`diabetes was estimated at $245 billion, including $176 billion in direct medical costs
`and $69 billion in reduced productivity (3). Spending on antidiabetic drugs ac-
`counted for $18.3 billion (3).
`Page 1 of 8
`
`1367
`
`(I)CrossMark
`
`Christian Hampp,’
`Vicky Borders-HemphilLZ
`David G. Moeny,’ and Diane K. Wysowski"
`
`‘Division of Epidemiology I, Office of Pharmaco
`vigilance and Epidemiology, Office of Surveil
`lance and Epidemiology, Center for Drug
`Evaluation and Research, U.S. Food and Drug
`Administration, Silver Spring, MD
`2Division of Medication Error Prevention and
`Analysis, Office of Medication Error Prevention
`and Risk Management, Office ofSurveillance and
`Epidemiology, Center for Drug Evaluation and
`Researdi, U. 5. Food and Drug Administration,
`Silver Spring, MD
`30ivlsion of Epidemiology ll, Office of Pharmaco
`vigilance and Epidemiology, Office of Surveil
`lance and Epidemiology, Center for Drug
`Evaluation and Researdw, US Food and Drug
`Administration, Silver Spring, MD
`Corresponding author: Christian Hampp, christian.
`hampp@fdahhs.gcv.
`Received 30 September 2013 and accepted 15
`January 2014.
`This article reflects the views of the authors and
`does not necessarily reflect the views or polides
`of the US Food and Drug Administration.
`@ 2014 by the American Diabetes Association.
`See http://creativeco
`pns.org/l' en 9 by
`nc nd/3.0/fordetails."fi’10gen EXI'II It 2178
`Mylan v. Biogen
`IPR 2018-01403
`
` @ U
`
`

`

`1368 Use of Antidiabetic Drugs in the U.S.
`
`Diabetes Care Volume 37, May 2014
`
`Although intensive lifestyle interven-
`tions (4) and bariatric surgery in obese
`diabetic patients (5–7) have been shown
`to improve or even reverse diabetes
`mellitus, most patients require pharma-
`ceutical management of their disease
`(8). Indeed, between 2007 and 2010,
`only 52.2% of diabetic patients had
`HbA1c levels ,7.0%, and only 14.3%
`met the combined goal of controlled
`HbA1c level, blood pressure, and LDL
`cholesterol
`level and nonsmoking
`status (8).
`The antidiabetic drug market is char-
`acterized by a number of new drugs
`that have been introduced during the
`last decade. These are the amylin analog
`pramlintide (approved in 2005); glucagon-
`like peptide 1 (GLP-1) analogs (exenatide
`immediate release, 2005; liraglutide,
`2010; exenatide extended release,
`2012); dipeptidyl peptidase-4 (DPP-4) in-
`hibitors (sitagliptin, 2006; saxagliptin,
`2009; linagliptin, 2011; alogliptin, 2013);
`a bile acid sequestrant (colesevelam,
`2009); a dopamine agonist (bromocriptine,
`2009); and a sodium glucose transport
`protein-2 inhibitor (canagliflozin, 2013).
`Several of these agents were also ap-
`proved as combination products con-
`taining metformin or simvastatin.
`The field of antidiabetic drugs experi-
`enced not only the addition of new
`drugs, but also emerging safety con-
`cerns of established drugs. In 2007, a
`meta-analysis (9) raised concerns re-
`garding the cardiovascular safety of ro-
`siglitazone, which was later pulled from
`the European market (10), and its use
`was severely restricted in the U.S. (11).
`Safety concerns also arose about the
`other remaining thiazolidinedione,
`pioglitazone, regarding its role in heart
`failure (12) and bladder cancer (13).
`This study describes the U.S. market
`trends for prescription antidiabetic
`drugs from 2003 through 2012. We
`highlight the market uptake of drugs ap-
`proved during this decade and how the
`use of thiazolidinediones was affected
`by recent safety concerns. Additional
`details by active ingredients are pro-
`vided for all antidiabetic drugs for the
`year 2012, including an analysis of con-
`comitant use.
`
`RESEARCH DESIGN AND METHODS
`We queried the IMS Health Vector One
`National and Total Patient Tracker data-
`bases for prescription antidiabetic drug
`
`use in the U.S. adult population (ages
`$20 years), annually from 2003 through
`2012. The IMS Health databases are
`large commercial prescription and pa-
`tient databases of drugs dispensed
`from outpatient retail pharmacies. IMS
`Health contracts with retail pharmacies,
`software providers, and pharmacy
`claims aggregators to obtain dispensed
`prescription data from two-thirds of the
`;59,000 U.S. retail pharmacies, ac-
`counting for approximately one-half of
`all retail prescriptions dispensed in the
`U.S. On an ongoing basis, IMS Health
`projects these data to the national level
`by using a proprietary method incorpo-
`rating geography, pay type, and class of
`trade (e.g., retail, independent, mass
`merchandisers).
`Based on IMS Health data and U.S.
`Census Bureau population estimates,
`we calculated the annual population-
`adjusted rates of antidiabetic drug users,
`and the proportion of insulin users and
`users of noninsulin antidiabetic drugs.
`These categories were not mutually ex-
`clusive, and users of noninsulin antidia-
`betic drugs included patients who used
`insulin in addition to their noninsulin an-
`tidiabetic drug. Next, we obtained the
`annual number of prescriptions dis-
`pensed by class for all antidiabetic drug
`classes and prescriptions dispensed by
`active ingredient for noninsulin antidia-
`betic drugs that were newly introduced
`to the market during the observation pe-
`riod. Additional analyses in the IMS
`Health databases focused on the annual
`use of thiazolidinediones, and, for the
`year 2012, the number of prescriptions
`and users by active ingredient. To
`investigate a shift from retail to mail-
`order pharmacies as a consequence of
`restricted distribution of rosiglitazone,
`we accessed the Symphony Health Sol-
`utions PHAST Prescription Monthly da-
`tabase, which, unlike the IMS Health
`databases used in our primary analyses,
`also contains mail-order prescriptions.
`This analysis was not restricted to
`adult use.
`We further extracted information on
`the concomitant use of antidiabetic
`drugs during the year 2012 using the
`Encuity Research Treatment Answers
`database. This database includes data
`from a survey of .3,200 office-based
`physicians representing 30 specialties
`across the U.S. who report on all patient
`activity during 1 typical workday per
`
`month. Encounter forms include basic
`patient demographic information, diag-
`noses, and treatments. Physicians are
`recruited by region and specialty based
`on the American Medical Association
`mailing list, which includes member
`and nonmember physicians. No filter is
`applied with regard to physician affilia-
`tion, and physicians in large health care
`systems are also invited to participate.
`We interpreted an office visit where
`more than one antidiabetic drug was
`mentioned as concomitant use of these
`drugs. In this context, drugs mentioned
`during an office visit include ongoing
`therapy, issuance of prescriptions, or
`the dispensing of drug samples. Combi-
`nation products were treated as con-
`comitant use of two antidiabetic drugs.
`The Treatment Answers database was
`also used to investigate diagnoses asso-
`ciated with the use of metformin. All
`data are nationally projected.
`Our analyses included all antidia-
`betic drugs available in 2012, with the
`exception of colesevelam. Colesevelam
`was approved for treatment of type 2
`diabetes in 2009, but it also carries an
`established indication for hypercholes-
`terolemia, thus not permitting us to
`analyze its use for the treatment of di-
`abetes in the IMS Health database.
`Bromocriptine was also approved
`for type 2 diabetes in 2009, and it is
`an established therapy for Parkinson’s
`disease, hyperprolactinemia, and acro-
`megaly. However, one bromocriptine
`product (Cycloset; Santarus, San Diego,
`CA) is exclusively indicated for the
`treatment of type 2 diabetes melli-
`tus, and we included Cycloset in our
`analyses.
`Summary statistics and linear regres-
`sion analysis to describe longitudinal
`trends in the total number of antidia-
`betic drug users were computed in Excel
`2010 (Microsoft, Redmond, WA). Popu-
`lation rates of drug use were calculated
`using U.S. Census Bureau estimates of
`the U.S. adult population (14).
`
`RESULTS
`Longitudinal Trends in Antidiabetic
`Drug Use
`According to IMS Health data, ;18.8
`million adults filled antidiabetic drug
`prescriptions from U.S. retail pharma-
`cies in 2012. This number represents a
`42.9% increase from 13.2 million in
`2003, and an average annual increase
`
`Page 2 of 8
`
`

`

`1369
`Hampp and Associates
`care.diabetesjou mals.org
`—
`
`by 650,229 (95% CI 519,490-780,968).
`On a per capita level, 81.3 per 1,000
`adults filled antidiabetic drug prescrip-
`tions in 2012, a 28.9% relative increase
`from 63.1 per 1,000 adults in 2003. Al-
`though rates of antidiabetic drug use
`have increased since 2003, the propor-
`tion of insulin users (27.1% in 2012) and
`the proportion of noninsulin antidia-
`betic drug users (86.7% in 2012) among
`all antidiabetic drug users remained
`constant over time.
`
`Figure 1A shows an increase in the
`total number of prescriptions for non-
`insulin antidiabetic drugs by 36.2%,
`from 88.8 million prescriptions in 2003
`to 120.9 million in 2012. During this de-
`cade, the use of biguanides (metformin)
`increased by 97.0% to 60.4 million
`
`prescriptions in 2012. The use of sulfo-
`nylureas remained constant in terms of
`prescription volume, but their share
`among noninsulin antidiabetic drug pre-
`scriptions decreased from 36.3% in 2003
`to 26.7% in 2012. During this period, the
`use of thiazolidinediones decreased by
`64.0%.
`
`Among the noninsulin antidiabetic
`drugs that were newly introduced to
`the market between 2003 and 2012,
`the DPP-4 inhibitor sitagliptin gained
`the largest share with 10.5 million pre-
`scriptions (single ingredient or combina-
`tion products) in 2012 (Fig. 13). Among
`GLP-1 analogs, immediate-release exe-
`natide (Byetta; Bristol-Myers Squibb,
`New York, NY) first entered the marked
`in 2005, and its use peaked in 2008 at 2.5
`
`million prescriptions. An increase in the
`use of liraglutide, which first assumed
`leadership of the GLP—1 analog market
`in 2011, was paralleled by a 49.5% de-
`cline in the use of exenatide-containing
`products. A once-weekly extended-
`release version of exenatide (Bydureon;
`Bristol-Myers Squibb) was approved by
`the U5. Food and Drug Administration
`(FDA) in January 2012 and represented
`20.3% of all exenatide prescriptions in
`2012 (data from both exenatide products
`are combined in Fig. 18).
`The use of thiazolidinediones is char-
`
`acterized by recent steep declines (Fig.
`2). Rosiglitazone-containing products
`declined from their peak in 2006, when
`12.7 million prescriptions were dis-
`pensed, to <1,000 prescriptions dis-
`pensed by retail pharmacies in 2012.
`The use of pioglitazone-containing
`products started a slow decline follow-
`ing its peak in 2008 when 14.2 million
`prescriptions were dispensed. This de-
`cline accelerated in recent years, and
`6.8 million prescriptions were dispensed
`in 2012, down 52.1% from the peak in
`2008. Using the Symphony Health Solu-
`tions PHAST Prescription Monthly data-
`base, we found 12,597 prescriptions of
`rosiglitazone—containing products dis-
`pensed in a retail or mail-order setting
`in 2012. Unlike analyses based on IMS
`Health data, this estimate was not re-
`stricted to adult use.
`
`Antidiabetic Drug Use in 2012
`In 2012, 154.5 million prescriptions
`were dispensed for antidiabetic drugs,
`78.4% of which were for noninsulin an-
`
`tidiabetic drugs (Table 1). About one in
`every two noninsulin antidiabetic drug
`prescriptions was for single-ingredient
`metfonnin, which was used by 11.8 million
`of 16.3 million noninsulin antidiabetic
`
`drug users (72.3%). More than one-quarter
`of noninsulin antidiabetic drug pre-
`scriptions was for sulfonylureas, and
`almost all ofthem were divided between
`
`three second-generation sulfonylureas
`(glipizide, glimepiride, and glyburide).
`DPP—4 inhibitors dominated the new class
`
`of incretin mimetic drugs, which also in-
`cludes the GLP—1 analog. In comparison,
`the use of some other drugs that were re-
`cently introduced to the diabetic market,
`such as pramlintide and bromocriptine,
`was infrequent.
`In 2012, 33.4 million insulin prescrip-
`tions were dispensed to 5.1 million
`
`[DAII others
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`
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`
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`
`Sitagliptin
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`Numberofprescriptions[millions]
`
`2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
`
`Figure 1—A: Trends in noninsulin antidiabetic drug prescriptions filled in US. retail pharmacies
`2003 2012. B: Prescriptions of recently approved noninsulin antidiabetic drugs filled in us.
`retail pharmacies, 2003 2012. AD, antidiabetic drugs. Source: IMS Health Vector One National.
`Page 3 of 8
`
`

`

`1370 Use of Antidiabetic Drugs in the U.S.
`
`Diabetes Care Volume 37, May 2014
`
`used the drug as monotherapy (Table
`2), consistent with recommendations
`by the American Diabetes Association
`and the European Association for the
`Study of Diabetes to use metformin as
`first-line therapy (20). Although metfor-
`min was used for other indications, the
`vast majority of prescriptions was for
`the treatment of diabetes.
`While the share of sulfonylurea use
`decreased, antidiabetic drugs that
`were approved during the last decade
`quickly gained significant market share.
`The most commonly prescribed new
`class was the DPP-4 inhibitors, which
`are available as oral tablets. Injectable
`GLP-1 analogs have also been widely
`used; however, between them, liraglu-
`tide has continued to gain market share
`while the use of exenatide declined. Lir-
`aglutide requires one daily injection,
`compared with twice-daily injections re-
`quired for immediate-release exena-
`tide, which may partially explain this
`trend. An extended-release version of
`exenatide, which requires only one
`weekly injection, was approved by the
`FDA in January 2012, and it reached a
`20% share of all exenatide prescriptions
`during that year.
`During the last decade, several com-
`bination products were approved, and
`their early rise in prescriptions has
`been documented before (15). Alexander
`et al. (15) found that 15% of treatment
`visits in 2004 were associated with oral
`combination products (first introduced
`in 2000), but this increase did not con-
`tinue (13% in 2007). We found that in
`2012, only 6.7% of noninsulin anti-
`diabetic drug prescriptions were for
`combination products, predominantly
`combinations of metformin with either
`sitagliptin or glyburide. While combi-
`nation products using metformin rep-
`resented a substantial share of DPP-4
`inhibitor–containing products, they played
`a smaller role among sulfonylureas or
`thiazolidinediones.
`Our analysis of the concomitant use
`of antidiabetic drugs in 2012 showed
`that only one-half to two-thirds of sul-
`fonylurea, DPP-4 inhibitor, thiazolidine-
`dione, and GLP-1 analog use was
`concomitant with metformin use. This
`occurred despite guideline recommen-
`dations of continuing metformin use
`when adding another noninsulin antidia-
`betic drug to therapy, unless metformin is
`contraindicated or not well-tolerated
`
`Figure 2—Thiazolidinedione prescriptions filled in U.S. retail pharmacies, 2003 2012. Source:
`IMS Health Vector One National.
`
`patients. The insulin market was domi-
`nated by long-acting human analog in-
`sulin, mostly insulin glargine, followed
`by fast-acting human analog insulin,
`mostly insulin aspart and insulin lispro.
`In 2012, metformin was predominantly
`used for the treatment of diabetes-
`related diagnoses (97.6%). Other uses
`were for gynecologic diagnoses (1.8%,
`predominantly for polycystic ovary dis-
`ease), disorders related to obesity (0.1%),
`or other diagnoses (0.5%).
`
`Concomitant Antidiabetic Drug Use in
`2012
`Concomitant use of more than one an-
`tidiabetic drug class in 2012 is displayed
`in Table 2 for the most commonly used
`antidiabetic drug classes. This table
`shows that 44.9% of metformin use
`was for monotherapy, 22.1% was con-
`comitant with the use of sulfonylureas,
`22.0% was concomitant with the use of
`DPP-4 inhibitors, and 9.7% was concom-
`itant with the use of long-acting insulin.
`In contrast, between 51.9% (GLP-1 ana-
`logs) and 66.6% (thiazolidinediones) of
`noninsulin antidiabetic drug use was
`concomitant with the use of metformin.
`Almost one-third of long-acting insulin
`use was concomitant with the use of
`fast-acting insulin, and, conversely, al-
`most two-thirds of fast-acting insulin
`use was concomitant with the use of
`long-acting insulin.
`
`CONCLUSIONS
`This study adds current and nationally
`projected estimates to previous studies
`describing the use of antidiabetic drugs
`(15–19). We documented a steady increase
`
`in the number of patients who used
`antidiabetic drugs and in the number
`of dispensed prescriptions in U.S. re-
`tail pharmacies. Our estimate of 18.8
`million antidiabetic drug users in 2012
`is identical to the Centers for Disease
`Control and Prevention estimate (1) of
`patients in whom diabetes has been di-
`agnosed (18.8 million in 2010). How-
`ever, our number should not be taken
`as the actual number of diabetic pa-
`tients because not every patient who
`receives a diagnosis of diabetes uses
`antidiabetic drugs, the number of pa-
`tients with diagnosed diabetes likely
`increased during the 2 years between
`the Centers for Disease Control and
`Prevention estimate and our estimate,
`and not all antidiabetic drugs are used
`solely for diabetes. Nevertheless, the
`fact that these numbers are so similar,
`although obtained through very differ-
`ent methodology, provides reassur-
`ance regarding data validity.
`Our study illustrated the roles that
`different antidiabetic drugs play in the
`management of diabetes; chief among
`them was metformin, which represents
`one of every two prescriptions for non-
`insulin antidiabetic drugs. This marks
`the continuation of a remarkable trend:
`in 1996, the year after metformin was
`approved in the U.S., 19.0% of all oral
`antidiabetic drug prescriptions were for
`metformin, and this proportion in-
`creased to 32.7% in 2001 (19). Almost
`11.8 million patients (62.7% of all pa-
`tients who received antidiabetic drugs)
`used single-ingredient metformin in
`2012 (Table 1), and 44.9% of patients
`to whom metformin was dispensed
`
`Page 4 of 8
`
`

`

`care.diabetesjouma|s.org
`
`Hampp and Associates
`
`1371
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`

`

`1372 Use of Antidiabetic Drugs in the U.S.
`
`Diabetes Care Volume 37, May 2014
`
`(20). Previous studies (21–25) have iden-
`tified the presence of contraindications
`among users of metformin; however,
`whether contraindications or lack of
`tolerability explain why metformin is
`not used more often with second-line
`antidiabetic drugs is subject to further
`research.
`A steep decline in the use of rosiglitazone-
`containing products after the publica-
`tion of the meta-analysis by Nissen and
`Wolski (9) reporting an association be-
`tween rosiglitazone and cardiovascu-
`lar events has been well-documented,
`both in the U.S. (26–32) and abroad
`(33–35). However, to our knowledge,
`our study is the first to also evaluate
`thiazolidinedione use patterns after
`rosiglitazone restrictions were imple-
`mented by the FDA in May 2011 (11).
`Since then, rosiglitazone-containing prod-
`ucts have been limited to patients already
`being successfully treated with these
`medicines, and to patients whose blood
`glucose level cannot be controlled with
`other antidiabetic drugs and who, after
`consulting with their health care pro-
`viders, do not wish to use pioglitazone-
`containing medicines. To implement this
`restriction, since November 2011, health
`care providers and patients had to be en-
`rolled in a special access program, and
`rosiglitazone-containing products could
`be obtained only through specially certi-
`fied mail-order pharmacies. Our analysis
`found 12,597 prescriptions of rosiglitazone-
`containing products dispensed in a retail
`or mail-order setting in 2012. Compared
`with ,1,000 rosiglitazone prescriptions
`detected in our primary analysis based
`on retail pharmacies, this number indi-
`cates that the majority of rosiglitazone
`was obtained through mail order. Never-
`theless, the overall use of rosiglitazone-
`containing products in 2012 was almost
`negligible. Pioglitazone-containing
`products represented almost all thia-
`zolidinedione use, with 6.8 million dis-
`pensed prescriptions in 2012. Yet, this
`number reached only half of the peak
`use in 2008, despite the approval of the
`first generic form of pioglitazone in
`August 2012, highlighting the impact
`of potential safety concerns. In November
`2013, the FDA announced the removal of
`restrictions for rosiglitazone on patients,
`prescribers, and pharmacies (36). Future
`research should describe the impact of
`relaxing prescription requirements on
`rosiglitazone use.
`
`onecassmaynotadduptototapatentcountsforthatcassbecausepatentscoudhaveusedmorethanonememberofthedrugcassn2012,butwoudonybecountedonceonthecasseve
`AD,antdabetcdrugs;NAD,nonnsunantdabetcdrug;TZD,thazodnedone;NPL,neutraprotamnesproSource:MSHeathVectorOneNatonaandTotaPatentTracker*Patentcountsacrossdrugsn
`
`49
`
`127,267
`229,552
`126,908
`207,487
`
`371,579
`
`109,526
`91,009
`345,653
`
`1000
`329
`671
`371
`629
`
`1000
`
`172
`194
`634
`
`human(sophane/reguar)
`
`ong-actng,nsunznc,nsun
`Anmansuns,humannsun
`
`nsunreguarhumansem-syntheszed
`
`nsunreguarhumanrecombnant
`nsunNPHhumansem-syntheszed
`
`18,810,311
`
`43
`
`343,360
`
`nsunNPHhumanrecombnant
`
`317,341
`
`nsunhuman/nsunNPHhuman
`
`371,341
`
`nsunsproprotamne/spro
`
`nsunNPL/nsunspro
`
`nsunaspartprotamne/nsunaspart
`
`519,504
`
`,01
`
`35
`
`42
`
`56
`
`78
`
`154,461,839
`
`Tota
`
`49
`
`Othernsuns
`
`1,164,300
`
`Humannsunfast-actng
`
`1,400,094
`
`1,884,245
`
`2,590,153
`
`ntermedate-actng
`
`Humannsun
`
`combnatons
`
`Humannsun
`
`combnatons
`
`Anaoghumannsun
`
`Patents(N)*
`
`ncass(%)
`
`Drug
`
`Patents(N)*
`
`Prescrptons,sharenNADornsun(%)
`
`Totaprescrptons(N)
`
`Drugcass
`
`Prescrptons,share
`
`Table1—Continued
`
`Page 6 of 8
`
`

`

`care.diabetesjournals.org
`
`Hampp and Associates
`
`1373
`
`Table 2—Concomitant therapy among the most common antidiabetic drug classes, 2012
`Concomitant with
`
`Use of this
`class
`
`No other
`antidiabetic drug Biguanides Sulfonylureas
`
`DPP 4
`inhibitors
`
`TZDs
`
`GLP 1
`analogs
`
`Insulin, analog human
`long acting
`
`Insulin, analog human
`fast acting
`
`Biguanides
`Sulfonylureas
`DPP 4
`inhibitors
`TZD
`GLP 1 analogs
`Insulin, analog
`human
`Long acting
`Fast acting
`
`44.9
`28.0
`
`25.5
`19.4
`37.3
`
`32.7
`25.7
`
`d
`
`61.0
`
`65.1
`66.6
`51.9
`
`31.7
`16.1
`
`22.1
`d
`
`16.4
`28.5
`17.3
`
`12.3
`4.6
`
`22.0
`15.4
`
`d
`
`14.9
`5.5
`
`8.0
`9.4
`
`5.3
`d
`
`8.7
`
`9.7
`6.2
`
`3.1
`,1.0*
`
`4.0
`3.7
`
`1.3
`5.6
`d
`
`4.8
`1.7
`
`9.7
`10.3
`
`8.7
`7.9
`18.7
`
`d
`64.1
`
`2.4
`1.9
`
`2.7
`,1.0*
`3.2
`
`31.4
`d
`
`Data are given as %. Row totals can exceed 100% because of patients using more than two antidiabetic drugs. TZD, thiazolidinedione. Source: Encuity
`Research Answer Generator. *Shares ,1.0% are not displayed.
`
`One strength of this study is the use
`of nationally projected data, without
`being limited to a certain health care
`setting or population. However, we
`were able to provide data only on anti-
`diabetic drug prescriptions dispensed
`from U.S. retail pharmacies. Using
`wholesale sales data obtained from
`the IMS Health National Sales Perspec-
`tive, we estimated that in 2012, 68% of
`noninsulin antidiabetic drug containers
`were shipped to retail pharmacies,
`while 21% were shipped to mail-order
`pharmacies and 11% to nonretail set-
`tings, including, among others, clinics,
`hospitals, and long-term care facilities.
`For insulin, 59%, 23%, and 18% of drug
`containers were shipped to retail phar-
`macies, mail-order pharmacies, or the
`nonretail setting, respectively. We expect
`that the total number of antidiabetic
`drug users is still a valid estimate, as
`most patients will fill a prescription for
`at least one antidiabetic drug in a retail
`pharmacy in a given year and, thus,
`would be included in our analysis. How-
`ever, users of our data should keep in
`mind that the total number of prescrip-
`tions dispensed applies only to the retail
`setting. Similarly, our data did not cap-
`ture the use of over-the-counter insulin.
`Further, while the sample of retail phar-
`macies is large, representativeness is not
`necessarily guaranteed, and changes in
`the sampling scheme could affect trend
`data.
`This study documented a 42.9% in-
`crease in the number of patients who
`filled antidiabetic drug prescriptions in
`U.S. retail pharmacies between 2003 and
`2012. Among 154.5 million antidiabetic
`
`drug prescriptions in 2012, metformin
`was the dominant noninsulin antidia-
`betic drug. Since 2003, several new
`classes of antidiabetic drugs have
`gained significant market share, most
`prominently DDP-4 inhibitors and
`GLP-1 analogs. This study further pro-
`vided patterns of thiazolidinedione
`use after restrictions were placed on
`rosiglitazone in 2011. In 2012, the use
`of rosiglitazone was almost negligible,
`and the use of pioglitazone decreased
`to half of its peak level from 2008. Fi-
`nally, our concomitancy analysis found
`that about one-third to one-half of
`sulfonylurea, DPP-4 inhibitor, thia-
`zolidinedione, and GLP-1 analog use
`was not accompanied by metformin
`use, despite recommendations in diabe-
`tes treatment guidelines.
`
`Acknowledgments. The authors thank Justin
`Mathew, Division of Epidemiology II, Office of
`Pharmacovigilance and Epidemiology, Office of
`Surveillance and Epidemiology, Center for Drug
`Evaluation and Research, U.S. Food and Drug
`Administration, for his assistance in the extrac
`tion of drug utilization data.
`Duality of Interest. No potential conflicts of
`interest relevant to this article were reported.
`Author Contributions. C.H. conceived and
`designed the study, acquired the data, per
`formed analysis and interpretation of the data,
`drafted the manuscript, and performed the
`statistical analysis. V.B. H. and D.G.M. con
`ceived and designed the study, acquired the
`data, performed analysis and interpretation
`of the data, and performed critical revision of
`the manuscript. D.K.W. conceived and de
`signed the study, and performed critical re
`vision of the manuscript. C.H. is the guarantor
`of this work and, as such, had full access to all
`the data in the study and takes responsibility for
`
`the integrity of the data and the accuracy of the
`data analysis.
`Prior Presentation. An earlier version of this
`study with data through 2011 was presented as a
`poster at the International Conference on Phar
`macoepidemiology and Therapeutic Risk Man
`agement, Barcelona, Spain, 23 26 August 2012.
`
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`1374 Use of Antidiabetic Drugs in the U.S.
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`Diabetes Care Volume 37, May 2014
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