PROVIL
(Pill buRden and cOmpliance in type-2 diabetic patients treated with VILdagliptin)

PROVIL
(Pill buRden and cOmpliance in type-2 diabetic patients treated with VILdagliptin)

Bisher liegen keine Ergebnisse nicht-interventioneller Studien zu GALVUS® oder EUCREAS® vor. Es sollen unter routinemäßigen Anwendungsbedingungen von GALVUS®/ EUCREAS® oder einer anderen dualen oralen antidiabetischen Therapie während eines sechsmonatigen Zeitraums in der alltäglichen klinischen Praxis Daten mit folgenden Zielsetzungen erhoben werden:
1. Erfassung der typischen Charakteristik der Patienten, bei denen sich der behandeln-de Arzt für eine Behandlung mit einer oral verabreichten antidiabetischen dualen The-rapie entschieden hat
2. Bedeutung der Polypharmakotherapie und Tablettenlast in der Beurteilung von Arzt und Patient
3. Beurteilung der Effizienz anhand HbA1c, sowie Beurteilung patientenbezogener End-punkte wie Hypoglykämie und Gewichtszunahme während einer Therapie mit
GALVUS® in freier Kombination mit Metformin oder EUCREAS® in Vergleich mit an-deren oral verabreichten antidiabetischen dualen Therapie-Regimen
4. Allgemeine ärztliche Beurteilung des Therapienutzens sowie der Verträglichkeit
5. Einsatz von GALVUS®/EUCREAS® im Praxisalltag entsprechend der Fachinformatio-nen
Im Beobachtungszeitraum auftretende unerwünschte Ereignisse werden dokumentiert und ausgewertet.

Galvus / Eucreas

2500

10000

Müller, Alfons

Phase IV Manager NIS

Novartis Pharma GmbH

Roonstr. 25

90429 Nürnberg

Deutschland

alfons.mueller@novartis.com

Telefon: 0911/273-12897

Telefax: 0911/273-15897

Novartis Pharma GmbH

Roonstr. 25

90429 Nürnberg

Deutschland

02.11.2011

Studie bereits abgeschlossen

2.2. Study design
This NIS was performed in accordance with the Freiwillige Selbstkontrolle für die Arzneimittelindustrie (FSA; Voluntary Self-Regulation of the Pharmaceutical Industry) -Code (07 May 2008, BAnz., No. 68, p. 1636) and the joint recommendations of the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM; Federal Institute for Drugs and Medical Devices) and the Paul-Ehrlich-Institute (PEI) for planning, implementation and analysis of an observational study (Anwendungsbeobachtungen [Draft version: 09 May 2007]) as well as the Verband forschender Arzneimittelhersteller (VFA; German Association of Research-based pharmaceutical companies) - Recommendations for the improvement of the quality and transparency of NISs from 31 January 2007 and 23 April 2007.
The aim was to investigate therapy courses and results under routine conditions. According to the definition of NISs no guidelines were given concerning therapy and implementation. The temporal frequency of examinations was to be according to practice routine. Additional examinations exceeding the usual extent were not required.
Treatment was to be only according to medical and therapeutic needs. It was not allowed to treat patients solely in order to include them into the NIS. There were no exclusion criteria, except for the contraindications mentioned in the respective summary of product characteristics (SmPC). The respective SmPC for GALVUS/ EUCREAS and the other oral antidiabetics also gave details on the indication and possible adverse reactions.
This multicenter NIS was to be performed in about 2.500 centers (general practitioners and internists). This was about 4% of the target group of general practitioners and internists in Germany and ensured that the population in the involved study centers was representative to the greatest possible extent. Treatment courses in a total of about 10.000 patients were to be documented. Approximately 7.500 patients with a GALVUS combination therapy with Metformin or a fixed combination therapy with EUCREAS and a further 2.500 patients under another dual oral antidiabetic-therapy were to be documented.
This NIS aimed to observe and to document patients of either sex, who up to now received an oral monotherapy for the treatment of their type-2 diabetes mellitus, and for whom the treating physician had decided to use a therapy with GALVUS in combination with Metformin/ EUCREAS or another dual combination therapy with oral antidiabetics. Fixed combinations with 2 active substances were not to be considered a monotherapy, but a dual therapy.
For all included patients written informed consent for documentation had to be obtained. The written informed consent had to be archived by the participating physician for 10 years.
To obtain meaningful results according to the aims, the duration of observation under therapy with GALVUS/ EUCREAS or another dual combination therapy with oral antidiabetics has been estimated to be 6 months.
According to routine practice it was expected, that in this time period interim examinations were performed. The documentation of findings was to take place at the start of observation as well as for a control examination after approximately 3 months and for the end of observation approximately 6 months after the time of inclusion. All case report forms (CRFs) reaching the assigned contract research organization (CRO) until February 2011 were taken into account for the statistical analysis.
At the start of observation (initial visit), demographic and diagnostic data, anamnesis of type-2 diabetes, and date of first diagnosis were documented. Additionally, data on diabetes control independent of the NIS and according to the SmPC, further laboratory parameters, vital signs, relevant prior and concomitant medication and diseases, oral antidiabetic dual therapy, current pill burden, impact of pill burden on physician and patient, and morbidity burden were gathered. In case control visits according to routine practice are performed (first control visit, after approximately 3 months) in addition to examinations specified in the SmPC, the following information could be gathered: date of examination, weight, data on diabetes control and further laboratory parameters independent of the NIS and according to the SmPC, changes in antidiabetic therapy, vital signs, premature discontinuation of therapy, documentation of adverse events.
At the end of observation (second control visit, approximately 6 months after start), a final examination was to be performed and the following was obtained: date of examination, weight, data on diabetes control and further laboratory parameters independent of the NIS and according to the SmPC, changes in antidiabetic therapy, vital signs, assessment of the oral dual antidiabetic therapy by the treating physician (efficacy, tolerability), premature discontinuation of therapy, continuation of oral dual antidiabetic therapy, documentation of adverse events.

3834

male and female adults with diabetes mellitus typ-2 and already treated with an oral antidiabetic monotherapy

15 Wochen

3.1.4.1.2. Laboratory parameters for the analysis of effectiveness - HbA1c
Overall population
Overall, decreases in HbA1c from the initial visit to the last visit were seen both for the mean (from 7.8 ± 1.2% to 6.9 ± 0.9%) and the median values (from 7.6% to 6.8%; Appendix, Table 06.02.1).
HbA1c values during the study and absolute differences compared to baseline are summarized for the 3 cohorts in Table 16. Relative differences to baselines can be found in the Appendix, Table 6.04.2.

2.5. Monitoring of adverse events
Each adverse event was to be documented in the CRF independent of its causal relationship to the study medication. The physician was to report start and duration of the event and to assess the intensity and the causal relationship as well as to document the outcome and potential counteractive measures.
In general serious AEs (SAEs) and non-serious AEs were differentiated. Both of these terms were used to describe adverse events regardless of their relationship to study drug. For the purpose of the statistical analysis, events were further distinguished according to their relationship to study drug. For an explanation of the respective definitions see Section 3.1.8.1.1.
SAEs were all events which
• resulted in death or were life-threatening
• required inpatient hospitalization or prolongation of existing hospitalization
• resulted in disability, incapacity or invalidity
• resulted in a congenital abnormality or a birth defect
• were considered medically significant by the physician or the pharmacovigilance department of the Novartis Pharma GmbH.
Inpatient hospitalization was not considered an SAE, if any of the following was the case:
• Hospital stays that had already been planned before entry into the NIS
• Elective hospital stays for treatment of prior diseases, which had no relationship to the disease, which was examined in this NIS or to the study medication.
• outpatient hospital treatments, which did not lead to hospitalization (in this context it had to be checked, if one of the other criteria was present, e.g. in case of a life-threatening event.)
• hospital treatment, that was part of the normal treatment or control of the disease examined in this NIS and that was not caused by an aggravation of the disease.
The assessment of the event as an SAE was only dependent on the presence of any of the above mentioned formal criteria and independent of the question if a causal relationship between the intake of the medication and the occurrence of the SAE was assumed.
In addition to the entry on the CRF all SAEs needed to be fully documented on the form „report of adverse events“ and – together with copies of the documentation forms – needed to be faxed to the pharmacovigilance department of Novartis Pharma GmbH within 24 hours of gaining knowledge.
The patient CRFs were examined by the CRO if data regarding AEs had been entered into the appropriate page and all CRF pages were carefully screened for hidden AEs. Table 2 gives an overview on all formal check procedures performed with regard to screening of AEs.

The impact of the pill burden according to the patient’s assessment and evaluation of the “morbidity burden” by the patient were analyzed.
Based on the patient questionnaire the following information was to be gathered:
 Correlation of pill burden, perception of disease and psychosocial strain
 Correlation of pill burden, domestic assistance and expenditure of time concerning management of medication
 Color and form of pills as a factor influencing compliance
 Influence of pill burden on compliance and medication errors
 Disease burden resulting from diabetes

2.8. Statistical methods
The statistical evaluation was done in a purely descriptive manner. The output tables were prepared using the statistical software program SAS® Version 9.2 for Windows.
For qualitative variables frequency tables were prepared and for quantitative variables the parameters for statistical distribution shown in Table 3 were calculated.
Table 3: Parameters for statistical distributions
Non-Missing Number of non-missing values
Median Smallest value, which exceeds 50% of the observed values when ordered in ascending order
Mean Arithmetic Mean
SD Standard deviation
Minimum Minimum of all observed values
Maximum Maximum of all observed values
1. Quartile Smallest value, which exceeds 25% of the observed values when ordered in ascending order
3. Quartile Smallest value, which exceeds 75% of the observed values when ordered in ascending order
P1 Smallest value, which exceeds 1% of the observed values when ordered in ascending order
P5 Smallest value, which exceeds 5% of the observed values when ordered in ascending order
P95 Smallest value, which exceeds 95% of the observed values when ordered in ascending order
P99 Smallest value, which exceeds 99% of the observed values when ordered in ascending order
For coding of plain text, the following coding systems were used:
Table 4: Coding systems
Further prior and concomitant diseases relevant to the indication MedDRA Version 13.1
Further prior and concomitant medication WHO DRLVersion December 2010
Current anti-diabetic therapy WHO DRLVersion December 2010
Adverse events MedDRA Version 13.1
Further details of the analysis were described in the statistical analysis plan (Version 0.2 of 7 April 2011).
In addition to the analysis of the overall population, a subgroup analysis by age group was performed (<65 years; ≥ 65 years). The results are presented in additional appendices to this report (Appendix <65 years and Appendix ≥ 65 years). The present report focuses on the analysis of the overall population. Additionally, it describes the subgroup analysis where appropriate.

During the observation period, the HbA1c values continuously decreased in all 3 cohorts. These decreases compared to baseline (absolute differences; mean ± SD) were more pronounced in the GALVUS (-0.9 ± 1.0%) and the EUCREAS cohort (-0.9 ± 1.2%) than in the other antidiabetics cohort ( 0.6 ± 1.0%; values for last documented control visit).
In analogy to this, the fasting glucose values continuously decreased in all 3 cohorts. The absolute decreases from baseline (mean ± SD) were more pronounced in the GALVUS ( 29.2 ± 41.7 mg/dl) and the EUCREAS cohort (-30.5 ± 42.8 mg/dl) than in the other antidiabetics cohort ( 20.4 ± 38.7 mg/dl).
Slight decreases in weight were observed for the patients in the GALVUS and EUCREAS cohort, while the weight in patients taking other oral antidiabetics remained the same.
At the end of the study, the physician assessed the efficacy of the treatment. Regardless of treatment cohort, the efficacy was assessed as “very good” or “good” for the majority of patients (83.4%). The percentage of “very good” efficacy assessments was higher in the GALVUS (47.4%) and EUCREAS (50.5%) cohort compared to the other oral antidiabetics (30.8%). A similar trend was seen when the assessments of “very good” and of “good” were added together.
The tolerability was also assessed as “very good” or “good” for the majority of patients (94.0%) regardless of treatment cohort. The percentage of “very good” tolerability assessments was higher in the GALVUS (56.4%) and EUCREAS cohort (62.8%) compared to the other oral antidiabetics (37.4%). A similar but less pronounced trend was seen when the assessments of “very good” and of “good” were added together.

During the observation period, a total of 499 AEs (total number of events, regardless of seriousness or relationship) were documented in 330 of 3834 patients (8.6%). In the individual cohorts, 77 AEs were reported in 50 of 603 patients on GALVUS (8.3%), 340 AEs were reported in 209 of 2198 patients on EUCREAS (9.5%) and 78 AEs were reported in 67 of 847 patients on other antidiabetics (7.9%). A further 4 events were reported in 4 patients without assignment to the 3 cohorts. In all 3 cohorts, AEs were most frequently reported for the System Organ Class (SOC) Investigations, followed by Gastrointestinal disorders in the GALVUS and EUCREAS cohort and by Vascular disorders in the other oral antidiabetics cohort. At the preferred term (PT) level, the most frequently reported AE was glycosylated hemoglobin increased, followed by blood glucose increased in all 3 cohorts.
In 25 patients on GALVUS (4.1%), 106 patients on EUCREAS (4.8%) and 21 patients on other oral antidiabetics (2.5%) a non-serious adverse drug reaction (nsADR) was documented, i.e. the relationship to treatment was assessed as certain, probable, possible, not assessable, or the assessment was missing. For 12 patients on GALVUS (2.0%), 48 patients on EUCREAS (2.2%) and 9 patients on other oral antidiabetics (1.1%) at least 1 event met the criteria for a serious adverse event without causal relationship (SAE). For 1 patient on GALVUS (0.2%), 14 patients on EUCREAS (0.6%) and 6 patients on other oral antidiabetics (0.7%) a serious adverse drug reaction (SADR; causality with regards to study drug: certain, probable, possible, not assessable, missing) was observed. A total of 4 patients (1 patient in the GALVUS cohort [event: lung neoplasm malignant, not related to treatment] and 3 patients in the EUCREAS cohort [events: convulsion and brain neoplasm, not related to treatment; cardiac failure, bile duct cancer and cardiac arrest, not related to treatment; and death, relationship to treatment not assessable) died during the observation period.

Overall, there were no major differences between the baseline characteristics of the CRF population (see Section 3.1.2) and the patient questionnaire population.
The composition of the sample of patients who filled in the patient questionnaire is given in Table 36 by sex and by age at initial visit.
Table 36: Baseline characteristics - sex and age at initial visit
Patients with filled in questionnaire
(N= 3843)
N %
Sex
Male 2128 55.4
Female 1687 43.9
Missing 28 0.7
Age categories
< 65 years 2134 55.5
≥ 65 years 1564 40.7
Missing 145 3.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.01; Table 10.02)

Slightly more of these patients were male than female and slightly more patients were in the younger age group (<65 years) compared to the older age group (≥ 65 years).
The mean duration of diabetes mellitus type-2 was 6.1 ± 5.1 years (median: 4.9 years; see Appendix, Table 10.03).
A summary of anamnestic diagnoses is given in Table 37.
Table 37: Baseline characteristics - anamnestic diagnoses
Categories Patients with filled in questionnaire
(N= 3843)
N %
Missing/no findings 369 9.6
Diabetic nephropathy 255 6.6
Diabetic neuropathy 493 12.8
Diabetic retinopathy 225 5.9
Hypertension 2979 77.5
Dyslipidemia 1898 49.4
Obesity 1965 51.1
CHD 630 16.4
PAD 188 4.9
History of myocardial infarction 180 4.7
Status post apoplectic stroke 117 3.0
CHD = Coronary heart disease, N = number of patients; % = percentage of patients, PAD= peripheral artery disease
(Source: Appendix, Table 10.04)
The most frequent anamnestic diagnosis at baseline was hypertension, followed by obesity and dyslipidemia.
The total number of tablets per day is given in Table 38 and the number of anti-diabetic tablets per day is given in Table 39.
Table 38: Baseline characteristics – Total number of tablets per day
Total number Patients with filled in questionnaire
(N= 3843)
N %
Total 3843 100.0
None 34 0.9
≤ 2 tablets 408 10.6
> 2 and ≤ 4 tablets 980 25.5
> 4 and ≤ 6 tablets 1028 26.7
> 6 and ≤ 8 tablets 626 16.3
> 8 tablets 643 16.7
Missing 124 3.2
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.05)
Table 39: Baseline characteristics – Number of antidiabetic tablets per day
Total number Patients with filled in questionnaire
(N= 3843)
N N
Total 3843 100.0
None 79 2.1
1 tablet 263 6.8
2 tablets 1931 50.2
> 2 and ≤ 4 tablets 1188 30.9
> 4 tablets 227 5.9
Missing 155 4.0
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.06)
With regard to the pill burden, the highest percentage of patients took ‘> 2 and ≤ 4 tablets’ or ‘> 4 and ≤ 6 tablets’ per day. When only considering the number of antidiabetic pills taken per day, about half of the patients took 2 tablets per day and a further 30.9% took ‘> 2 and ≤ 4 tablets’ per day. More than 4 tablets a day were only taken by 5.9% of the patients.
In the following sections the respective questions and answers are shown by sex. Patients for which information on sex was missing are included in the total column but are not presented in a separate column.
3.2.2. Burden and perception of disease
The influence of the tablet number on how sick patients felt is summarized in Table 40.
Table 40: „The number of tablets I must take has an influence on how sick I feel“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 1013 26.4 527 24.8 479 28.4
Agree 1351 35.2 719 33.8 623 36.9
Disagree 926 24.1 546 25.7 372 22.1
Strongly disagree 526 13.7 322 15.1 200 11.9
Missing 27 0.7 14 0.7 13 0.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.07)
The perception of disease also showed a correlation with the pill burden. In total, 61.6% of the patients agreed or strongly agreed to the statement that the number of tablets they were to take had an influence on how sick they felt. This percentage was slightly higher in female than in male patients.
3.2.3. Domestic assistance and of time needed
The need for help in order to prepare the intake of tablets is summarized overall and by sex in Table 41.
Table 41: „I need help at home in order to prepare the intake of tablets for the day/week“ - classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 308 8.0 149 7.0 157 9.3
Agree 439 11.4 234 11.0 199 11.8
Disagree 722 18.8 384 18.0 330 19.6
Strongly disagree 2347 61.1 1347 63.3 988 58.6
Missing 27 0.7 14 0.7 13 0.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.08)
Overall and in both subgroups by sex, the need for help in order to prepare the intake of tablets per day was relatively low.
The mean amount of time needed on average per day to prepare the tablets was 6.6 ± 7.4 minutes (median: 5.0 minutes) for the total population, 7.1 ± 7.5 minutes for female patients (median: 5.0 minutes) and 6.2 ± 7.0 for male patients (median: 5.0 minutes). For further details see Appendix, Table 10.09.
3.2.4. Impact of color and form of pills
The impact that the appearance of the tablets (color and form) had on the patient is summarized in Table 42.
Table 42: „The appearance of the tablets is important for me to correctly assign my drugs“ - classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 929 24.2 457 21.5 466 27.6
Agree 1440 37.5 782 36.7 647 38.4
Disagree 829 21.6 488 22.9 335 19.9
Strongly disagree 620 16.1 388 18.2 227 13.5
Missing 25 0.7 13 0.6 12 0.7
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.10)
In total, 61.7% of the patients agreed or strongly agreed to the statement that the appearance of tablets was important for them to correctly assign their drugs. This percentage was slightly higher in female (66.0%) than in male patients (58.2%).
A further question concerning the impact of color and form was, if a change in appearance makes it harder for the patient to correctly take their tablets. This could e.g. be the case, if a change in compound leads to a difference in appearance of the tablets. The responses to this question are summarized in Table 43.
Table 43: „The correct use of drugs is harder for me when their appearance changes“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 925 24.1 455 21.4 463 27.4
Agree 1401 36.5 748 35.2 643 38.1
Disagree 894 23.3 542 25.5 346 20.5
Strongly disagree 600 15.6 372 17.5 223 13.2
Missing 23 0.6 11 0.5 12 0.7
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.11)
Slightly more than 60% of the patients overall agreed or strongly agreed that the correct use of drugs was harder for them when the appearance changed. Again, this percentage was slightly higher in female than in male patients.
3.2.5. Influence of pill burden on medication errors
The patients’ responses concerning the influence of pill burden on medication errors are summarized in Table 44.
Table 44: „I am concerned about accidentally forgetting pills or taking the wrong tablets/dose“ – classified by sex)
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 714 18.6 358 16.8 351 20.8
Agree 1133 29.5 574 27.0 548 32.5
Disagree 1182 30.8 698 32.8 475 28.2
Strongly disagree 788 20.5 485 22.8 300 17.8
Missing 26 0.7 13 0.6 13 0.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.12)
Slightly less than half of the patients (48.1%) were concerned about accidentally forgetting pills or taking the wrong tablets/dose. The percentage of patients who agreed or strongly agreed to this statement was higher in female (53.3%) than in male patients (43.8%).
 
3.2.6. Disease burden resulting from diabetes
The influence that suffering from type-2 diabetes had on the patients summarized in Table 45.
Table 45: „My daily life is influenced by the fact that I suffer from type-2 diabetes“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 949 24.7 499 23.4 440 26.1
Agree 1534 39.9 794 37.3 729 43.2
Disagree 1021 26.6 633 29.7 384 22.8
Strongly disagree 320 8.3 194 9.1 123 7.3
Missing 19 0.5 8 0.4 11 0.7
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.13)
With regard to the statement „my daily life is influenced by the fact that I suffer from type-2 diabetes“ almost two-thirds of the patients (64.6%) agreed or strongly agreed. The percentage of female patients who agreed or strongly agreed was higher (69.3%) than the respective percentage of male patients (60.7%).
The patients’ responses concerning their worries about potential late effects of diabetes are given in Table 46.
Table 46: „I am worried about the possible late effects of diabetes (e.g. blindness, dialysis, heart and circulatory diseases“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 1316 34.2 680 32.0 620 36.8
Agree 1689 44.0 918 43.1 763 45.2
Disagree 643 16.7 421 19.8 220 13.0
Strongly disagree 156 4.1 94 4.4 60 3.6
Missing 39 1.0 15 0.7 24 1.4
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.14)
In total, 78.2% of the patients were worried about the possible late effects of diabetes. Again, this percentage was higher in female (82.0%) than in male patients (75.1%).
The consequences that the patients were most concerned about are summarized in Table 47.
Table 47: „I am most concerned because of the following consequences (multiple response)“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Blindness 1896 49.3 981 46.1 897 53.2
Diabetic foot (circulatory disturbances, poorly healing wounds, amputation) 1677 43.6 882 41.4 780 46.2
Dialysis (dialysis after kidney failure) 1588 41.3 821 38.6 753 44.6
Heart and circulatory diseases (e.g. myocardial infarction, stroke) 2315 60.2 1294 60.8 1004 59.5
Missing 554 14.4 332 15.6 216 12.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.15)
Regardless of sex, the consequences that patients were most concerned about were heart and circulatory diseases (60.2%) followed by blindness (49.3%).
A summary of the patients’ responses concerning the ability to maintain weight is given in Table 48.
Table 48: „It is hard for me to maintain my weight“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 1552 40.4 779 36.6 767 45.5
Agree 1322 34.4 735 34.5 576 34.1
Disagree 674 17.5 428 20.1 242 14.3
Strongly disagree 276 7.2 178 8.4 91 5.4
Missing 19 0.5 8 0.4 11 0.7
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.16)
In total, 74.8% of the patients agreed or strongly agreed that it was hard for them to maintain their weight. Again, this percentage was higher in female (79.6%) than in male patients (71.1%).
The responses concerning fear of hypoglycemia are provided in Table 49.
Table 49: „I have fear of hypoglycemia (typical symptoms: sweating, trembling, nausea, heart palpitations)“ – classified by sex
Total Male Female
N % N % N %
Total 3843 100.0 2128 100.0 1687 100.0
Strongly agree 610 15.9 292 13.7 312 18.5
Agree 1075 28.0 555 26.1 512 30.3
Disagree 1589 41.3 908 42.7 672 39.8
Strongly disagree 543 14.1 360 16.9 178 10.6
Missing 26 0.7 13 0.6 13 0.8
N = number of patients; % = percentage of patients
(Source: Appendix, Table 10.17)
Less than half of the patients (43.9%) agreed or strongly agreed that they had fear of hypoglycemia. Again, this percentage was higher in female (48.8%) than in male patients (39.8%).

Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients.