Patient Preference and Adherence
`
`Open Access Full Text Article
`
`Dovepress
`
`open access to scientific and medical research
`
`O r i g i nA L re s eAr c h
`
`Multinational internet-based survey of patient
`preference for newer oral or injectable
`Type 2 diabetes medication
`
`Marco dacosta
`DiBonaventura1
`Jan-samuel Wagner 1
`cynthia J girman 2
`Kimberly Brodovicz2
`Qiaoyi Zhang3
`Ying Qiu3
`sri-ram Pentakota 3
`Larry radican 3
`1health sciences Practice, Kantar
`health, new York; 2epidemiology,
`3global health Outcomes,
`Merck, Whitehouse station,
`new Jersey, UsA
`
`correspondence: Marco DiBonaventura
`health sciences Practice, Kantar health,
`11 Madison Avenue, 12th Floor,
`new York, nY 10010, UsA
`Tel +1 212 706 3988
`Fax +1 212 647 7659
`email marco.dibonaventura@
`kantarhealth.com
`
`Background: The prevalence of Type 2 diabetes mellitus continues to rise. Although
`glucagon-like peptide-1 (GLP-1) analog and dipeptidyl peptidase-4 (DPP-4) inhibitor
`medications are effective, there are differences between these products, including method
`of administration (injectable versus oral). The objective of this study was to examine patient
`preferences (and predictors of preferences) for two different medication profiles, one similar to
`a GLP-1 analog (liraglutide) and another similar to a DPP-4 inhibitor (sitagliptin).
`Methods: Internet survey data were collected in two waves (wave 1, n = 2402; wave 2, n = 1340)
`using patients from the US and Europe. Patients were presented with two hypothetical medica-
`tion profiles (“drug A” and “drug B”, resembling sitagliptin and liraglutide, respectively) and
`asked to report their preferences.
`Results: Most patients in wave 1 and wave 2 reported that overall they would prefer a drug with
`the sitagliptin-like profile (81.9% and 84.4%, respectively) over a drug with the liraglutide-like
`profile (18.1% and 15.6%, respectively), and .80% of patients reported that they would be
`able to take a drug with the sitagliptin-like profile as directed by their physician for a longer
`period. The likelihood of preferring the sitagliptin-like profile significantly increased as age
`(odds ratio [OR] = 1.02) and importance placed on method of administration (OR = 1.32)
`increased (P , 0.05). Although the sitagliptin-like profile was preferred by the majority of
`patients in all subgroups, a lower proportion of patients with obesity, with weight gain, with
`A1C values above target, and who exercised preferred the sitagliptin-like profile compared
`with those without obesity (77.0% versus 87.9%), without weight gain (77.8% versus 86.7%),
`with A1C values at or below target (79.0% versus 86.5%), and who did not exercise (81.6%
`versus 86.4%), respectively (P , 0.05).
`Conclusions: This research suggests that patients (across geographies) prefer an oral medica-
`tion with a profile resembling sitagliptin to an injectable medication with a profile resembling
`liraglutide.
`Keywords: Type 2 diabetes, medication preference, sitagliptin, liraglutide
`
`Introduction
`Type 2 diabetes mellitus (T2DM) is considered to be a major epidemic worldwide.1
`According to the International Diabetes Federation, the prevalence of diabetes is
`currently estimated at 8.5% in Europe and 11.7% in North America and the Caribbean,
`with prevalence expected to rise to 10.0% and 13.6%, respectively, by 2030.1
`As prevalence figures rise, so do health care costs. The American Diabetes Association
`previously estimated that diabetes was responsible for $116 billion in direct medical
`costs and $58 billion in indirect costs in the US in 2007.2
`
`submit your manuscript | www.dovepress.com
`Dovepress
`DOI: 10.2147/PPA.S14477
`
`397
`Patient Preference and Adherence 2010:4 397–406
`© 2010 DiBonaventura et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access
`article which permits unrestricted noncommercial use, provided the original work is properly cited.
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00001
`
`

`

`DiBonaventura et al
`
`Dovepress
`
`As a result of the United Kingdom Prospective Diabetes
`Study (UKPDS) and other studies, guideline committees have
`recommended that patients with TD2M maintain a hemoglobin
`A1C level of less than 7%.3,4 For many patients with T2DM,
`oral antihyperglycemic agents are used as first-line therapies
`because of the combination of efficacy and physicians’ percep-
`tions of patient preference.5,6 Some oral antihyperglycemic
`agents have been associated with adverse events, such as weight
`gain and hypoglycemia, which have been linked to nonadher-
`ence, treatment dissatisfaction, and diminished health-related
`quality of life (HRQoL).7–9 Partly as a consequence, persistence
`with first-line oral antihyperglycemic agents has been poor,
`with estimates in the T2DM managed care population ranging
`from 34% to 60% for discontinuation after 12 months.10,11
`Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-
`like peptide-1 (GLP-1) mimetics or analogs, which rely on the
`gastrointestinal hormones that are part of the incretin system
`for the treatment of T2DM, provide a therapeutic alternative
`to common oral antihyperglycemic agents (eg, sulfonylureas,
`thiazolidinediones). These newer medications may be
` particularly useful in cases where other therapies are not
`well tolerated or as complementary therapies when ongoing
`therapies do not allow the patient to reach their glycemic
`target.12 GLP-1 receptor agonists and DPP-4 inhibitors have
`been shown to be noninferior to other oral antihyperglyce-
`mic agents, lowering mean A1C levels by 0.97% and 0.74%,
`respectively.13 Additionally, hypoglycemic episodes and
`weight gain, reported with other oral antihyperglycemic
`agents, are infrequent or absent with these new agents.14
`Despite both targeting the incretin system, GLP-1 recep-
`tor agonists and DPP-4 inhibitors do have several differences.
`First, all GLP-1 receptor agonists are injectable medications.
`Previous studies have shown that patients prefer additional
`oral agents over injectable agents because of fear of injec-
`tions and the desire to avoid them.6,15,16 Moreover, one study
`found that persistence with these agents was poor, with only
`28.7% treatment continuation at one year follow-up among
`treatment-naïve patients with T2DM.17 Second, some GLP-1
`receptor agonists may have efficacy and weight advantages
`over DPP-4 inhibitors, suggesting a possible relationship with
`improved HRQoL because previous studies have shown an
`association between weight loss and HRQoL.16,18,19 Third,
`patients on GLP-1 therapies have reported higher rates of
`gastrointestinal-related complications, including nausea and
`vomiting, compared with DPP-4 inhibitors.18,20
`Although incretin-based medications may potentially help
`to overcome some of these barriers to successful T2DM man-
`agement, the positive and negative effects of these drugs should
`
`be further analyzed in the context of patient preference to assess
`the likelihood of long-term patient acceptability. Although phy-
`sicians play a crucial role in determining the best therapeutic
`intervention for their patients, patient preferences should also
`be considered. The achievement of glycemic control goals rely
`to a large extent on treatment compliance and adherence. The
`objective of the current study was to examine patient prefer-
`ences when presented with profiles similar to a GLP-1 analog
`(liraglutide) and a DPP-4 inhibitor (sitagliptin).
`
`Patients and methods
`recruitment
`Data were collected in two waves with patients from the US,
`France, Italy, Germany, Spain, and the UK. Patients were
`recruited from the 2008 and 2009 US National Health and
`Wellness Survey (NHWS), an annual Internet-based ques-
`tionnaire developed by Consumer Health Sciences/Kantar
`Health, and the Ailment Panel of Lightspeed Research.
`These panels are designed to be nationally representative
`and mimic the demographic composition of each country’s
`total adult population. Further details of the methodology and
`comparisons between NHWS and other sources have been
`described elsewhere.21 Participants who were over the age of
`18 years, diagnosed with T2DM by a health care professional,
`used only metformin monotherapy to treat their diabetes,
`and provided informed consent were eligible to participate
`in the study. The study protocol was approved by the Essex
`Institutional Review Board.
`Wave 1 was conducted between June 2009 and July 2009,
`and wave 2 was conducted between December 2009 and
` January 2010. All patients who completed the first wave
`(n = 2402) were recontacted and asked to participate in the
`second wave (n = 1340, 56.8% response rate). The second wave
`was conducted because newer data became available after wave
`1 from a head-to-head trial of sitagliptin and liraglutide (Novo
`Nordisk Interim Financial Report, August 6, 2009). The A1C
`efficacy difference reported in the head-to-head trial (0.6%)
`was twice that assumed in wave 1, which had been based
`on data from two different clinical trials of sitagliptin and
`liraglutide.22,23 Data from the head-to-head trial on glycemic
`efficacy and weight loss were used for the medication profiles
`in wave 2. However, because neither gastrointestinal side
`effect nor blood pressure data from the head-to-head trial were
`provided in the Novo Nordisk report, data from Nauck et al
`were used for gastrointestinal tolerability and blood pressure
`effects.22,23 The Novo Nordisk report noted that the safety data
`of liraglutide in the head-to-head study were comparable with
`what was observed in previous clinical studies of liraglutide.
`
`398
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`Patient Preference and Adherence 2010:4
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00002
`
`

`

`Dovepress
`
`Patient preference for diabetes medications
`
`Therefore, it was deemed acceptable to use data from both trials
`in constructing the profiles. Only side effects or other effects
`that were statistically significant or clinically meaningful in
`the trials were included in the profiles.
`Although the head-to-head trial suggested that sitagliptin
`was associated with a small weight loss of 1 kg, it was decided
`conservatively to assume no weight loss for sitagliptin in the
`profile. Finally, A1C baseline values were converted to average
`blood glucose values based on a published equation.24 It was
`assumed that patients would better comprehend blood glucose
`values, which are based upon day-to-day self monitoring, as
`opposed to A1C values, which are periodically tested labora-
`tory measures.
`
`Measures
`Medication preference variables
`Patients were shown two medication profiles at each wave of
`the study (Table 1), one of which was similar to the profile
`of sitagliptin (noted only as “drug A” to the patients) and
`
`the other of which was similar to liraglutide (only noted as
`“drug B”). Patients were given the following instructions:
`“Below are hypothetical descriptions of two medications
`that treat Type 2 diabetes–drug A and drug B (Note: neither
`one is an insulin). Assume taking metformin alone does not
`lower your blood sugar enough and that your physician offers
`you a choice of either drug A or drug B to be added to your
`current diabetes therapy of metformin. Assume that both
`medications cost you the same amount.” All patients were
`asked which they would prefer (drug A or drug B), which they
`would prefer to take first knowing they could later switch or
`add on other therapies if needed, and which they would be
`able to take as directed by their physician for a longer period
`of time. Additionally, for all patients who preferred drug B
`or preferred to take drug B first, they were asked whether
`their preference would change if drug A had been used by
`physicians and patients for two years and drug B had just
`become available. The patients were also asked whether their
`preference would change if drug A cost less than drug B.
`
`Table 1 Medication profiles shown to patients in wave 1 and wave 2
`Drug A
`
`Drug B
`
`Wave 1
`how you take the medication
`Blood sugar lowering efficacy
`
`side effects
`
`Oral tablet taken once a day
`if you have a blood sugar reading of 183, taking
`this oral medication can lower it to about 164
`(individual results may vary)
`generally similar to a sugar pill with very low
`risk of hypoglycemia (ie, low blood sugar)
`
`Other effects
`
`– Weight: no change
`– Blood pressure: no change
`
`injection (needle) self-administered once a day
`if you have a blood sugar reading of 183, using this injection
`medication can lower it to about 154 (individual results
`may vary)
`– nausea (occurs in 11 to 19% of patients), vomiting (occurs
`in 5 to 7% of patients) and diarrhea (occurs in 8 to 15%
`of patients), which goes away for most patients after
`about1 month (individual results may vary)
`– Other side effects generally similar to a sugar pill with very
`low risk of hypoglycemia (ie, low blood sugar)
`– Weight: loss of about 6.2 pounds (individual results may vary)
`– Blood pressure: decrease in systolic blood pressure of about
`2 to 3 mm of mercury (hg) (individual results may vary)
`
`Wave 2
`how you take the medication
`Blood sugar lowering efficacy
`
`side effects
`
`Oral tablet taken once a day
`if you have a blood sugar reading of 197,
`taking this oral medication can lower it to
`about 171 (individual results may vary)
`generally similar to a sugar pill with very low
`risk of hypoglycemia (ie, low blood sugar)
`
`injection (needle) self-administered once a day
`if you have a blood sugar reading of 197, using this
`injection medication can lower it to about 154 (individual
`results may vary)
`– nausea (occurs in 11 to 19% of patients), vomiting (occurs
`in 5 to 7% of patients) and diarrhea (occurs in 8 to 15% of
`patients), which goes away for most patients after about
`1 month (individual results may vary)
`– Other side effects generally similar to a sugar pill with very
`low risk of hypoglycemia (ie, low blood sugar)
`– Weight: loss of about 7.7 pounds (individual results
`may vary)
`– Blood pressure: decrease in systolic blood pressure
`of about 2 to 3 mm of mercury (hg) (individual results
`may vary)
`Note: In the EU countries, blood sugar efficacy was displayed as 10.1 and 9.1 for drug A and 10.1 and 8.5 for drug B in wave 1, and 10.9 and 9.5 for drug A and 10.9 and 8.5
`for drug B in wave 2. similarly, weight loss was displayed in kilograms for drug B (2.8 kg in wave 1 and 3.5 in wave 2).
`
`Other effects
`
`– Weight: no change
`
`– Blood pressure: no change
`
`Patient Preference and Adherence 2010:4
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`399
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00003
`
`

`

`DiBonaventura et al
`
`Dovepress
`
`preference groups were analyzed according to demographic
`and health history variables using Chi-square tests for
`categoric variables and t-tests for continuous variables.
`Overall preference based on wave 2 data was then assessed
`in a logistic regression controlling for all demographic
`and patient characteristic variables, which were associated
`with preference with a P , 0.20 in the unadjusted analysis.
`Attribute importance items were forced into the model,
`regardless of the unadjusted P value, because these were
`directly related to preference. All analyses were performed
`using the SAS software version 9.1.
`
`Results
`In wave 1, 2402 patients completed the survey, comprising
`400 patients from each country (with the exception of
`402 patients from France). Patients were equally split between
`male (n = 1222, 50.9%) and female (n = 1180, 49.1%),
`although patients were mostly white (n = 2057, 85.6%), had
`health insurance (n = 1611, 67.1%), and had less than a college/
`university degree (n = 1717, 71.5%). The mean age across the
`sample was 54.5 (standard deviation [SD] = 12.7) years.
`Based on the medication profiles provided, the majority
`of patients (81.9%) responded that overall they would prefer
`the drug with the sitagliptin-like profile (drug A) over the
`drug with the liraglutide-like profile (drug B), prefer to take
`the drug with the sitagliptin-like profile first (82.8%), and
`believed they could take the drug with the sitagliptin-like
`profile for longer (83.4%, Table 2). Among the patients
`who preferred the liraglutide-like profile (drug B) overall or
`preferred to take a drug with the liraglutide-like profile first
`(n = 292), 63.7% maintained their preference if told the drug
`
`Table 2 Frequency and percentage of patients who chose each
`medication under varying scenarios
`
`Drug A
`(sitagliptin-
`like profile)
`n
`%
`
`Drug B
`(liraglutide-
`like profile)
`n
`%
`
`These additional questions were asked because, at the time
`of the surveys, sitagliptin had been available on the market
`for approximately two years and liraglutide was just being
`launched, and liraglutide is more costly than sitagliptin.
`
`reasons for preference
`After participants reported their overall preference for drug
`A or B and which drug they would prefer to take first, they
`were asked to rank the importance of the following reasons
`for their preference: how you take the medication (oral or
`injection), blood sugar lowering, side effects (nausea, vomit-
`ing, and diarrhea), and other effects (weight loss and blood
`pressure decrease).
`
`Demographics
`Country of residence (US, France, Italy, Germany, Spain,
`UK), age, gender, race/ethnicity (white versus nonwhite),
`education (college/university degree versus less than college/
`university degree), health insurance (yes versus no), and
`employment status (full-time, part-time, self-employed, not
`employed but looking for work, not employed and not look-
`ing for work, retired, on disability, student, or homemaker)
`were assessed for all patients.
`
`health history
`Patients were asked to report the presence of comorbid dys-
`lipidemia, hypertension, and obesity. Patients also reported
`any health problems experienced in the last 12 months
`(cardiovascular event, nausea or vomiting, constipation or
`diarrhea, weight gain, have not experienced any of the listed
`problems), diabetes management steps (try to maintain a
`healthy diet, try to maintain an exercise regimen, use glu-
`cose monitor), diabetes educational program participation
`(yes versus no), date of last A1C test (within the last three
`months, 4–6 months ago, 7–12 months ago, over a year
`ago, or never), and what their physician said about their A1C
`level when last tested (below the target, at the target, higher
`than the target, physician did not provide test results, or do
`not remember).
`
`statistical analysis
`Preferences under each scenario (overall preference, pref-
`erence if you knew you could switch later, preference for
`medication you could take longer, preference if drug B had
`just become available, and preference if drug B was more
`expensive) were reported for both study waves. All other anal-
`yses focused exclusively on the overall preference assessed
`in study wave 2. Differences between the drug A and B
`
`1098
`1110
`
`81.9%
`82.8%
`
`242
`230
`
`18.1%
`17.2%
`
`Wave 1 preferences
`Which drug would you prefer
`Which drug would you prefer to
`take first if you could switch later
`Which drug could you take for
`longer
`Wave 2 preferences
`Which drug would you prefer
`Which drug would you prefer to
`take first if you could switch later
`13.5%
`86.5%
`181
`1159
`Which drug could you take for longer
`Note: Significantly more patients preferred drug A in each scenario (p’s , 0.001).
`
`1117
`
`83.4%
`
`223
`
`16.6%
`
`1131
`1139
`
`84.4%
`85.0%
`
`209
`201
`
`15.6%
`15.0%
`
`400
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`Patient Preference and Adherence 2010:4
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00004
`
`

`

`Dovepress
`
`Patient preference for diabetes medications
`
`Table 3 reasons for preference ranked by importance
`Ranked 1st
`Drug A
`(sitagliptin-like
`profile)
`n
`650
`
`%
`57.5%a
`
`Drug B
`(liraglutide-
`like profile)
`n
`%
`12.9%
`27
`
`how you take the medication
`(oral or injection)
`Blood sugar lowering
`side effects (nausea, vomiting,
`and diarrhea)
`Other effects (weight loss
`and blood pressure decrease)
`Note: aThe percentage of patients who noted each reason as the most important
`was significantly different between the two groups (p , 0.001).
`
`with the liraglutide-like profile had just become available,
`and 65.1% maintained their preference if a drug with the
`liraglutide-like profile was more expensive.
`In wave 2, out of the total sample (n = 1340), 266
`(19.9%) participants were from Germany, 111 (8.3%) were
`from France, 212 (15.8%) were from Italy, 208 (15.5%)
`were from Spain, 265 (19.8%) were from the UK, and 278
`(20.8%) were from the US. The majority of participants were
`male (n = 713, 53.2%), white (n = 1213, 90.5%), had health
`insurance (n = 881, 65.7%), and had less than a college/
`university degree (n = 943, 70.4%). The mean age across
`the wave 2 sample was 55.4 (SD = 12.1) years. Those who
`participated in both wave 1 and wave 2 were significantly
`older (55.4 years versus 53.4 years, respectively, P , 0.001),
`and more likely to be white (90.5% versus 79.5%, P , 0.001)
`and male (53.2 versus 47.9, P = 0.01) than those who only
`participated in wave 1.
`Although the glycemic efficacy of the drug with the
`liraglutide-like profile was improved in the medication profile
`in wave 2, the preference results were consistent with wave 1.
`Most patients (84.4%) responded they would prefer the drug
`with the sitagliptin-like profile (drug A) over the drug with
`the liraglutide-like profile (drug B) overall, prefer to take
`the drug with the sitagliptin-like profile first (85.0%), and
`believed they could take the drug with the sitagliptin-like
`profile longer (86.5%, Table 2). Among those patients who
`preferred the liraglutide-like profile overall or preferred to
`take the drug with the liraglutide-like profile first (n = 251),
`57.0% maintained their preference if told the drug had just
`become available, and 71.3% maintained their preference if
`told the drug was more expensive.
`The reasons for the overall preference in wave 2 were
`then compared between patients who preferred the drug with
`the sitagliptin-like profile and those who preferred the drug
`with the liraglutide-like profile (Table 3). “How you take the
`medication, oral versus injectable” was ranked as the most
`important reason for their preference by the majority of
`those who preferred the drug with the sitagliptin-like profile
`(57.5%). Conversely, “blood sugar lowering” was ranked as
`the most important reason for their preference by the major-
`ity of those who preferred the drug with the liraglutide-like
`profile (56.0%). All reasons were ranked differently between
`the preference groups. Specifically, for patients who pre-
`ferred the drug with the sitagliptin-like profile, “how you
`take the medication” (57.5% versus 12.9%, P , 0.001)
`and “side effects” (17.9% versus 4.3%, P , 0.001) were
`significantly more likely to be ranked as the most important
`reason for their preference. Conversely, for patients who
`
`261
`202
`
`18
`
`23.1%
`17.9%a
`
`1.6%
`
`117
`9
`
`56
`
`56.0%a
`4.3%
`
`26.8%a
`
`preferred the drug with the liraglutide-like profile, “blood
`sugar lowering” (56.0% versus 23.1%, P , 0.001) and “other
`effects” (26.8% versus 1.6%, P , 0.001) were significantly
`more likely to be ranked as the most important reason for
`their preference.
`Group differences were then analyzed between patients
`with a preference for the drug with the sitagliptin-like
`profile and patients with a preference for the drug with
`the liraglutide-like profile (Table 4). Patients who preferred
`the sitagliptin-like profile were significantly older, and were
`less likely to be female, be white, have comorbid obesity,
`have experienced weight gain in the past 12 months, have
`maintained a healthy diet, have maintained an exercise regi-
`men, have participated in a diabetes educational program,
`and have higher A1C levels than their targets the last time they
`were tested (all P , 0.05). Differences among countries and
`employment groups were also observed (all P , 0.05).
`Logistic regression was conducted and included all
`predictors of overall preference in wave 2 at the P , 0.20
`level, as well as all attribute importance items (Table 5). The
`likelihood of preferring the sitagliptin-like profile signifi-
`cantly increased with increasing age (odds ratio [OR] = 1.02,
`95% confidence interval [CI]: 1.01–1.04) or the importance
`placed on method of administration (oral versus injectable,
`OR = 1.32, 95% CI: 1.15–1.52). Conversely, the likelihood of
`preferring the sitagliptin-like profile was significantly lower
`in those with obesity (OR = 0.54, 95% CI: 0.38–0.75), weight
`gain in the last year (OR = 0.62, 95% CI: 0.44–0.87), those
`with an A1C above target (OR = 0.59, 95% CI: 0.41–0.83), and
`those who tried to maintain an exercise regimen (OR = 0.68,
`95% CI: 0.49–0.96), compared with those without obesity,
`without weight gain in the last year, those with A1C at or
`below target, and those who did not try to maintain an exer-
`cise regimen, respectively. Although the odds for preferring
`
`Patient Preference and Adherence 2010:4
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`401
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00005
`
`

`

`DiBonaventura et al
`
`Dovepress
`
`Table 4 Patient characteristics and overall medication preference
`Total
`
`n
`
`266
`111
`212
`208
`265
`278
`
`713
`627
`
`425
`120
`99
`51
`
`18
`
`433
`107
`8
`79
`
`459
`881
`
`127
`1213
`
`% of total
`sample
`
`19.9%
` 8.3%
`15.8%
`15.5%
`19.8%
`20.8%
`
`53.2%
`46.8%
`
`31.7%
` 9.0%
` 7.4%
` 3.8%
`
` 1.3%
`
`32.3%
` 8.0%
` 0.6%
` 5.9%
`
`34.3%
`65.8%
`
` 9.5%
`90.5%
`
`Drug A (sitagliptin-
`like profile)
`n = 1131 (84.4%)
`n
`Row %
`
`P
`
`Drug B (liraglutide-
`like profile)
`n = 209 (15.6%)
`n
`Row %
`
`214
`99
`185
`188
`205
`240
`
`619
`512
`
`357
`96
`88
`42
`
`10
`
`381
`80
`6
`71
`
`375
`756
`
`114
`1017
`
`798
`
`80.5%
`89.2%
`87.3%
`90.4%
`77.4%
`86.3%
`
`86.8%
`81.7%
`
`84.0%
`80.0%
`88.9%
`82.4%
`
`55.6%
`
`88.0%
`74.8%
`75.0%
`89.9%
`
`81.7%
`85.8%
`
`89.8%
`83.8%
`
`19.5%
`10.8%
`12.7%
`9.6%
`22.6%
`13.7%
`
`13.2%
`18.3%
`
`16.0%
`20.0%
`11.1%
`17.6%
`
`44.4%
`
`12.0%
`25.2%
`25.0%
`10.1%
`
`18.3%
`14.2%
`
`10.2%
`16.2%
`
`52
`12
`27
`20
`60
`38
`
`94
`115
`
`68
`24
`11
`9
`
`8
`
`52
`27
`2
`8
`
`84
`125
`
`13
`196
`
`146
`
`,0.001
`
`0.01
`
`0.01
`
`0.06
`
`0.04
`
`0.84
`
`Country
`germany
`France
`italy
`spain
`United Kingdom
`United states
`Gender
`Male
`Female
`Employment
`employed full-time
`employed part-time
`self-employed
`not employed, but
`looking for work
`not employed and
`not looking for work
`retired
`On disability
`student
`homemaker
`Insurance status
`no health insurance
`health insurance
`Race
`non-white
`White
`Education
`Less than college/
`university degree
`college/university degree
`Diagnosed comorbidity
`Dyslipidemia
`hypertension
`Obesity
`Health problems
`in last 12 months
`cardiovascular event
`(eg, heart attack, stroke)
`nausea or vomiting
`constipation or diarrhea
`Weight gain
`Diabetes management steps
`i try to maintain a healthy diet
`i try to maintain an
`exercise regimen
`i use a glucose monitor
`and test strips
`Participated in diabetes
`educational program
`Yes
`no
`
`944
`
`396
`
`571
`641
`430
`
`39
`
`217
`515
`343
`
`1054
`559
`
`835
`
`471
`869
`
`70.5%
`
`29.6%
`
`42.6%
`47.8%
`32.1%
`
` 2.9%
`
`16.2%
`38.4%
`25.6%
`
`78.7%
`41.7%
`
`62.3%
`
`35.2%
`64.9%
`
`333
`
`478
`531
`331
`
`29
`
`174
`432
`267
`
`877
`456
`
`693
`
`383
`748
`
`84.5%
`
`84.1%
`
`83.7%
`82.8%
`77.0%
`
`74.4%
`
`80.2%
`83.9%
`77.8%
`
`83.2%
`81.6%
`
`83.0%
`
`81.3%
`86.1%
`
`63
`
`93
`110
`99
`
`10
`
`43
`83
`76
`
`177
`103
`
`142
`
`88
`121
`
`15.5%
`
`15.9%
`
`16.3%
`17.2%
`23.0%
`
`25.6%
`
`19.8%
`16.1%
`22.2%
`
`16.8%
`18.4%
`
`17.0%
`
`18.7%
`13.9%
`
`0.55
`0.13
`,0.001
`
`0.15
`
`0.09
`0.68
`,0.001
`
`0.01
`0.02
`
`0.06
`
`0.03
`
`(Continued)
`
`402
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`Patient Preference and Adherence 2010:4
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00006
`
`

`

`Dovepress
`
`Table 4 (Continued)
`
`Time of last A1C test
`Within the past 3 months
`4–6 months ago
`7–12 months ago
`Over a year ago
`never
`What doctor said at last test
`(of those who had a test)
`A1c was below the target
`A1c was at the target
`A1c was higher than the target
`My physician did not provide
`me with the lab results
`i don’t remember
`
`Age
`Years of T2DM diagnosed
`Importance of diabetes
`medication attributes
`(unimportant to important)
`side effects
`Method of administration
`(oral vs injectable)
`effectiveness of medication
`experience of prescribing
`physician with medication
`Out-of-pocket costs
`of medication
`
`Total
`
`n
`
`823
`310
`113
`59
`35
`
`220
`533
`371
`83
`
`98
`
`M
`55.35
`6.24
`
`3.92
`3.86
`
`4.49
`4.11
`
`3.42
`
`Patient preference for diabetes medications
`
`Drug A (sitagliptin-
`like profile)
`n = 1131 (84.4%)
`n
`Row %
`
`Drug B (liraglutide-
`like profile)
`n = 209 (15.6%)
`n
`Row %
`
`% of total
`sample
`
`61.4%
`23.1%
`8.4%
`4.4%
`2.6%
`
`16.4%
`39.8%
`27.7%
`6.2%
`
`7.3%
`
`SD
`12.13
`5.88
`
`1.17
`1.23
`
`0.84
`0.96
`
`1.43
`
`691
`265
`91
`53
`31
`
`188
`466
`293
`67
`
`86
`
`M
`55.89
`6.22
`
`3.91
`3.90
`
`4.47
`4.10
`
`3.42
`
`84.0%
`85.5%
`80.5%
`89.8%
`88.6%
`
`85.5%
`87.4%
`79.0%
`80.7%
`
`87.8%
`
`SD
`12.13
`5.87
`
`1.19
`1.22
`
`0.85
`0.97
`
`1.43
`
`132
`45
`22
`6
`4
`
`32
`67
`78
`16
`
`12
`
`M
`52.45
`6.35
`
`3.98
`3.65
`
`4.55
`4.13
`
`3.43
`
`16.0%
`14.5%
`19.5%
`10.2%
`11.4%
`
`14.6%
`12.6%
`21.0%
`19.3%
`
`12.2%
`
`SD
`11.79
`5.95
`
`1.04
`1.29
`
`0.77
`0.85
`
`1.46
`
`P
`
`0.42
`
`0.02
`
`P
`,0.001
`0.78
`
`0.35
`0.008
`
`0.26
`0.67
`
`0.94
`
`the sitagliptin-like profile were significantly lower, there
`was an overall preference for the sitagliptin-like profile in
`these subgroups (adjusted percentages for preferring the
`sitagliptin-like profile: those with obesity = 77.0% versus
`those without obesity = 87.9%; those who experienced
`weight gain in the last year = 77.8% versus those who did
`not experience weight gain in the last year = 86.7%; those
`with an A1C above target = 79.0% versus those with an A1C at/
`below target = 86.5%; those who tried to maintain an exercise
`regimen = 81.6% versus those who did not try to maintain
`an exercise program = 86.4%). No other variable, including
`country, was a significant predictor of preference.
`
`Discussion
`Medication preferences for hypothetical sitagliptin-like and
`liraglutide-like agents were assessed in T2DM patients taking
`metformin monotherapy who would be eligible to add a new
`diabetes drug if they could not adequately control their blood
`sugar with metformin. Significantly more patients preferred
`
`the sitagliptin-like profile. Patients also were significantly
`more likely to prefer to take the drug with the sitagliptin-
`like profile first and more likely to report that they could
`take the drug with the sitagliptin-like profile as directed by
`their physician for a longer period of time. Among those
`who preferred the liraglutide-like profile, approximately
`one-third would have preferred the sitagliptin-like profile
`if the liraglutide-like drug was newer or more expensive.
`It is important to note that these preferences were consistent
`between wave 1 and wave 2. Although wave 2 used a
`liraglutide-like profile with greater weight reduction and
`glycemic efficacy relative to wave 1, this essentially had no
`effect on preferences.
`Because of the liraglutide-like profile’s weight loss and
`glycemic efficacy attributes, it was not surprising that a
`smaller proportion of patients with obesity, with weight gain
`in the last year, with A1C values above target, or who tried to
`maintain an exercise regimen preferred the sitagliptin-like
`profile compared with those without obesity, without weight
`
`Patient Preference and Adherence 2010:4
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`403
`
`Novo Nordisk Exhibit 2393
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00007
`
`

`

`DiBonaventura et al
`
`Dovepress
`
`Table 5 Likelihood of preference for the drug with the sitagliptin-
`like profile (drug A) over the drug with the liraglutide-like profile
`(drug B)
`
`factor. Similarly, the majority of those who preferred the
`liraglutide-like profile ranked glycemic efficacy and weight
`loss as the most important factors. Overall, these findings
`suggest an overwhelming preference among T2DM patients
`for an oral medication with a profile like the DPP-4 inhibitor,
`sitagliptin, even with slightly lower glycemic efficacy and
`a neutral weight loss profile. When patients were given the
`opportunity to change their preference if the drug with the
`liraglutide-like profile was newer or more expensive, about
`one-third of patients did so. The results of our survey are
`generally consistent with the findings of a recent study by
`Jendle et al, which demonstrated that Swedish patients with
`T2DM were willing to pay considerable amounts of money to
`avoid injections and nausea, and to lose w