Patient adherence in type 2 diabetes:
What’s the issue and how to address it
Anthony Barnett
University of Birmingham and Heart of England
NHS Foundation Trust, UK
Definition of compliance and persistence
Compliance: extent to which a patient acts in accordance with the prescribed
interval and dose of dosing regimen
Persistence: accumulation of time from initiation to discontinuation of therapy
Adherence: encompasses both
Prescribed regimen for 12 months
Fully compliant for 12 months
Fully persistent for 12 months
Partially compliant
Non-persistent (stopped therapy before 12 months)
Non-compliant and non-persistent
Non-acceptance (does not start therapy)
So what really happens when you fill a prescription?
PERSISTENCE
120
100 Metformin monotherapy
Persistent patients (%)
Sulphonylurea monotherapy
M+SU polytherapy
80
60
40
20
0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104
Weeks of therapy
Persistence Persistence
Study period Study groupa n SD
(in days)b rate (%)c
1 year Metformin (M) 4,033 183.8 142.7 51.06
(360 days) Sulphonylurea 11,234 183.1 141.8 50.86
(SU)
M+SU 661 111.1 117.4 30.86
2 YEARS Metformin 915 296.7 285.1 41.21
(720 days) Sulphonylurea 2983 274.3 276.5 38.10
M+SU 158 121.9 186.9 16.93
US population 2002. J Int Med Res. 2002;30:71.
So what really happens when you fill a prescription?
COMPLIANCE
100
compliant to therapy (%)
Patients remaining
80
60 65.06 64.64 63.07 60.54
40 44.42
35.76
20
0
1 Year (360 days) 2 Years (720 days)
Metformin Sulphonylurea Metformin + Sulphonylurea
Compliance Persistence
Study period Study groupa n SD
(in days)b rate (%)c
1 year Metformin (M) 4033 234.2 110.8 65.06
(360 days) Sulphonylurea 11,234 232.7 113.6 64.64
(SU)
M+SU 661 159.9 115.3 44.42
2 YEARS Metformin 915 454.1 232.2 63.07
(720 days) Sulphonylurea 2983 435.9 232.6 60.54
M+SU 158 257.5 228.2 35.76
US population 2002. J Int Med Res. 2002;30:71.
Diabetes Audit and Research in Tayside Study (DARTS)
• Study population
– All people with Type 2 Diabetes living in Tayside, Scotland
(~420,000)
– First prescription for oral anti-diabetes drug from 1 January 1993
onward
– Follow-up to 31 December 1995 with at least 12 months of
prescriptions
Total time drug prescribed
= Adherence index
Total time of follow-up
Donnan PT et al. Diabet Med. 2002;19:279-284.
Adherence index by type of therapy
Monotherapy Sulphonylurea 31
Metformin 34
Polytherapy Sulphonylurea 19
Metformin 13
Donnan PT et al. Diabet Med. 2002;19:279-284.
Once the patient has ACCEPTED treatment,
is everything fine?
Retrospective, cohort study of
community pharmacy records (N=2,325)
100
Continuous hypertensive users (%)
90
80
70
60
50
Men
40
Women
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10
Years after first prescription
Van Wijk et al. J Hypertens. 2005;23:2101-2107.
Does it matter?
Lessons from hypertension: improved outcome
40 44
All-cause hospitalisation risk (%)
39
36
30
30
27
20
10
0
1-19 20-39 40-59 60-79 80-100
Level of compliance (%)
Sokol et al. Med Care. 2005;43:521-530.
Does it matter?
Lessons from hypertension: improved BP control
*
Patients with BP control* (%)
40 42%
30 33% 32%
20
10
0
High Medium Low
(≥ 80%) (50%–79%) (15
Time (years)
Adapted from: Heine RJ et al. BMJ. 2006;333:1200-1204.
The treatment complexity in type 2 diabetes drives
non-adherence to management strategies
Medication for Complex Diabetes
A 42-year-old woman’s regimen for
treating complex diabetes includes…
• At least 15 types of oral medication
• 2 over-the-counter products
• 7 to 10 injections
• 4 blood tests
…per day, costing over $1,800 a month
retail
Source: Dr. John Buse, The New York Times
Current treatment paradigms for type 2 diabetes
are not “user-friendly”
Mild to moderate hyperglycaemia (HbA1C 15 mmol/L Glibenclamide, -0.2 (-0.3 to 0.0)
UKPDS 34. Lancet. 1998:352:854-865. n=at baseline; Kahn et al (ADOPT).
N Engl J Med. 2006;355(23):2427-2443.
Hypoglycaemia
The major limiting factor to achieving intensive glycaemic
control for people with type 2 Diabetes
Briscoe VJ et al. Clin Diab. 2006;24:115-121.
Clinical consequences of hypoglycaemia
• Hospital admissions:
– Prospective study1 of well-controlled elderly T2D patients—25% of
hospital admissions for diabetes for severe hypoglycaemia
• Increased mortality:
– 9% in a study2 of severe SU-associated hypoglycaemia
• Road accidents caused by hypoglycaemia events3:
– 45 serious events per month
1. Diab Nutr Metab. 2004;17:23-26. 2. Horm Metab Res Suppl. 1985;15:105-111. 3. BMJ. 2006;332:812.
Multicentre study funded by Dept for
Transport
Determine the frequency of
hypoglycaemia in type 2 Diabetes
treated with SUs and insulin for
differing duration
Compare frequencies with
type 1 Diabetes
Prospective study over 9-12 months
of patients with good glycaemic
control
Documented severe and mild
hypoglycaemia prospectively,
supplemented with CGM x 2
UK Hypoglycaemia Study Group. Diabetologia. 2007;50:1140-1147.
Hypoglycaemia in type 2 diabetes:
sulphonylureas vs insulin
• In patients treated for 6,000 US patients over 6 months
90
80
70 77 *
Adherence rate (%)
60
50
54
40
30
20
10
0
Metformin and Glyburide Glyburide/Metformin
Comparison of adjusted adherence rates in patients receiving metformin and
glyburide combination therapy and those receiving fixed-dose glyburide/metformin
combination therapy. *P = 0.001.
Clin Ther. 2002;24:3.
FDA on fixed-dose combination therapy (2005) –
advantages
• Advantages of fixed-dose combination drug therapy:
– Better adherence to a therapeutic regimen
– Patient convenience
– Economy (cost savings)
– Generation of information regarding drug compatability
and drug interactions
Federal Register. 1971;36(33):3126-3127. Am J Cardiol. 2005;96:28K-33K.
Fixed-dose combination therapy – conclusions
• In many conditions, including diabetes, combination therapy
is inevitable
• Poor adherence is common and significantly affects outcome
• FDC reduce non-adherence by ~25%
• FDC may improve long-term outcomes and makes life easier
for the adherent
Improving adherence
• We have or will have:
– Better tolerated drugs with low risk of hypoglycaemia and weight
gain, even weight loss!
– Fixed-dose combinations for some
– Possibility of once-weekly injectables coming through
The missing link:
good rapport between patient, family, and healthcare
professionals, including multi-professional support
Helping patients to accept their condition and
adhere to a management plan
Diagnosis of Type 2 Diabetes = loss of patient’s accustomed state of health
Patient’s willpower and ability to improve outcomes depend on degree
of acceptance of the serious nature of their condition
Relationship between patient and healthcare
professionals critical in this process
Lacroix A et al. Schweiz Rundsch Med Prax. 1993;82:1370-1372.
The need for good patient-healthcare professional
rapport is essential to driving treatment adherence
“My healthcare professional has “I don’t really monitor my blood
helped me understand my blood glucose levels. It doesn’t seem
glucose results and the that important.
importance of regular testing.
The physician never asks me my
I feel more in control of my numbers or measurements, so
diabetes.” why am I doing it?”
Motivating patients to achieve and maintain glycaemic
control will drive treatment adherence
“I’ve reached my glucose
target by eating properly,
exercising more, and
taking my medicine.”
“This is great news.
Continue with the good
work and keep your blood sugar
under control – you’ll feel better for it!”
Heisler M et al. Diabetes Care. 2005;28:816-822.
Establish a partnership between the patient and the
healthcare professional
Establish rapport
Agree on
mutual agenda
Exchange
information
Work together to:
Discuss importance of Build confidence that
implementing change change is possible
Challenges in improving patient understanding
35% recalled receiving advice
about their medication
15% knew the mechanism of action
Patient knowledge of their therapy
of oral anti-diabetes
agents
10% taking sulphonylureas knew
that they could cause hypoglycaemia
20% taking metformin knew it
could cause GI side effects
Expectations regarding side effects should be appropriately managed
Browne DL et al. Diabet Med. 2000;17:528-531.
Treatment adherence can only be achieved by ensuring
appropriate treatment goals
Unrealistic weight loss goals in obese patients seeking treatment
Outcome Weight (lbs) % Reduction
Initial 218 0
consultation
N = 60 Obese Women
Dream 135 38
Happy 150 31
Acceptable 163 25
Disappointed 180 17
Foster et al. J Consult Clin Psychol. 1997;65:79.
A multi-disciplinary team has a significant impact on
glycaemic control and hospital admissions
HbA1c Hospitalizations
Hospitalizations/1,000 person-months
0 30
Change in HbA1c from baseline (%)
-0.2 25
-0.4
20
-0.6
15
-0.8
10
-1.0
5
-1.2
-1.4 0
Control Multi-disciplinary Control Multi-disciplinary
team team
Sadur CN et al. Diabetes Care. 1999;22:2011-2017.
Impact of implementing an educational program via a
multi-disciplinary team
Variable Period of time after attending education courses
0 months 12 months
FPG (mmol/L) 10.2 8.7*
HbA1c (%) 8.9 7.8*
Body weight (kg) 83.0 81.0*
Systolic BP (mmHg) 154.0 143.0*
Diastolic BP (mmHg) 95.0 87.0*
Cholesterol (mmol/L) 6.2 5.4*
Triglycerides (mmol/L) 2.8 2.1*
*Significant improvement versus 0 months.
Gagliardino JJ et al. Diabetes Care. 2001;24:1001-1007.
Clear benefits of a multi-disciplinary team approach
in type 2 diabetes care
Improved Improved quality
glycaemic control1,2 of life1
Improved treatment Decreased
adherence1,2 CV risk2
Improved Higher patient
patient follow-up1 satisfaction1
Lower risk of Decreased healthcare
complications2 costs2
1. Codispoti C et al. J Okla State Med Assoc. 2004;97:201-204. 2. Gagliardino JJ et al. Diabetes Care. 2001;24:1001-1007.
Personalized care is paramount
• When dealing with a complex chronic disease
such as type 2 diabetes:
“. . . the guidance does not override the individual responsibility of
healthcare professionals to make decisions appropriate to the
circumstances of the individual patient, in consultation with the patient
and/or guardian or carer, and informed by the summary of product
characteristics of any drug they are considering.”
NICE Clinical Guidelines for the Management of Type 2 Diabetes. May 2009.
Need for personalized care: the benefits versus risks of
diabetes therapy must be assessed for each patient
Personalised care in type 2 diabetes
• The healthcare professional must agree with the individual
patient on their glycaemic target, how this can be achieved,
and measures of success
Guidelines are guidelines, not absolutes
Summary and conclusions
• Patient adherence to agreed management plans is the major
challenge in type 2 diabetes
• Poor adherence is due to many factors, including:
– tolerability issues, complexity of the disease and its co-morbidities,
lack of knowledge and support
• Therapeutic advances can help with the problem of adherence:
– modern drugs may be better tolerated with lower risk of hypoglycaemia
and weight gain
– increasing availability of fixed-dose combination therapies
• Multi-disciplinary care and a good relationship between the
patient and healthcare professionals can improve long-term
outcomes
Personalized care should be the
cornerstone of good diabetes management
Patient adherence in type 2 diabetes:
What’s the issue and how to address
Anthony Barnett
University of Birmingham and Heart of England
NHS Foundation Trust, UK