Transcript Document

Development Committee
Scientific Committee
• Keith Bowering, MD, FRCPC
• Alice Y. Y. Cheng, MD, FRCPC
• Jean-Marie Ekoé, MD, CSPQ, PD
• Lawrence A. Leiter, MD, FRCPC, FACP, FAHA
• Jean-François Yale, MD, CSPQ, FRCPC
Educational Committee
• John T. Axler, MD, CCFP, FCFP
• Carl Fournier, MD, CCFP
• Stewart B. Harris, MD, MPH, FCFP, FACPM
Faculty/Presenter Disclosure
• Faculty: [Speaker’s name]
• Relationships with commercial interests:
–
–
–
–
Grants/Research Support:
Speakers Bureau/Honoraria:
Consulting Fees:
Other:
Disclosure of Commercial
Support
• This program has received financial support from Merck Canada Inc.
in the form of an educational grant.
• This program has received in-kind support from Merck Canada Inc.
in the form of logistical support.
• Potential for conflict(s) of interest:
– [Speaker name] has received [payment/funding, etc.] from Merck Canada Inc.
– Merck Canada Inc. benefits from the sale of the products that will be
discussed in this program: Sitagliptin (Januvia®), Combination
Sitagliptin/Metformin (Janumet®).
Mitigating Potential Bias
• The information presented in this CME program is based on recent
information that is explicitly ‘‘evidence-based’’.
• This CME Program and its material is peer reviewed and all the
recommendations involving clinical medicine are based on evidence
that is accepted within the profession; and all scientific research
referred to, reported, or used in the CME/CPD activity in support or
justification of patient care recommendations conforms to the
generally accepted standards.
Learning Objectives
• At the end of this program, participants will be
able to:
– Discuss and determine barriers to achieving glycemic
control
– Identify factors contributing to patients’ nonadherence to antihyperglycemic medications
– Assess and apply strategies to improve adherence
– Determine adherence success strategies that can be
integrated into and adapted to clinical practice
Overview
•
•
•
•
•
•
Patient case
Challenges in achieving glycemic targets
Identifying non-adherence
Factors contributing to non-adherence
Strategies to improve adherence
Practice reflection
Opening Discussion
Questions for you…
What is the prevalence of diabetes
in Canada?
1.
2.
3.
4.
1-3%
3-6%
6-9%
>10%
Diabetes in Canada: Prevalence of
Diagnosed Diabetes by Age and Gender
Prevalence of diagnosed diabetes among individuals aged ≥1 year,
by age group and gender, 2008/09
Overall Prevalence
30
Females
6.4%
Males
7.2%
Total
6.8%
Prevalence (%)
25
20
15
10
5
0
Age group (years)
1-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
Prevalence increases with age; increase is sharpest after age 40 years.
Prevalence is highest in individuals aged 75 to 79 years.
Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa, 2011.
≥85
Canada
In a 2013 Canadian study of
over 5000 patients, what percentage
had achieved the following A1C values:
1. ≤7%
50% of patients with type 2 diabetes achieved an
A1C of ≤7%.
2. ≤8%
78% of patients achieved an A1C ≤8%.
3. ≤9%
91% patients achieved an A1C ≤9%.
Leiter LA et al. Can J Diabetes. 2013;37(2):82-89.
DM-SCAN: A1C Values Achieved
in Primary Care
N=5123
100%
86%
78%
80%
% of Patients
91%
67%
60%
50%
40%
28%
20%
0%
Target
Target
Achieved Achieved
≤6.5%
≤7.0%
≤7.5%
≤8%
A1C (%)
Leiter LA et al. Can J Diabetes. 2013;37(2):82-9.
≤8.5%
≤9.0%
DM-SCAN: Duration of Diabetes
and A1C ≤7%
% of Patients with A1C ≤7%
80%
62%
60%
50%
39%
40%
20%
0%
<5 years (n=1249)
5-10 years (n=1891)
>10 years (n=1518)
Duration of Diabetes (years)
Leiter LA et al. Can J Diabetes. 2013;37(2):82-9.
Group Discussion
Let’s discuss Sarah’s case
Sarah
AGE: 69
Medical History/Previous Medical Records
BP: 125/78 mmHg
• Controlled hypertension and dyslipidemia
BMI: 33.3
kg/m2
Current Medications
• Ramipril 10 mg qd
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
• T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months
of lifestyle management
– Dose increased to 1000 mg bid 6 months
ago
– Gliclazide initiated 3 months ago at last visit
when A1C was 7.5%
Current Laboratory Results
• A1C: 7.5%
• LDL-C: 1.9 mmol/L
• eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• What would you do with this patient
at this point?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
• Ramipril 10 mg qd
Medical History/Previous Medical Records
•
•
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
– Gliclazide initiated 3 months ago at last visit when A1C
was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• What might account for the fact that
Sarah’s A1C level has not changed since
her last visit?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
• Ramipril 10 mg qd
Medical History/Previous Medical Records
•
•
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
– Gliclazide initiated 3 months ago at last visit when A1C
was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Challenges in Achieving
Glycemic Goals
• Physician-related
– Failure of some clinicians to adopt a treat-to-target approach1
– Suboptimal dosing of available therapies1
• Medication-related
– Inability of any single agent’s mechanism of action to target all
core defects of type 2 diabetes2
– Access to and cost of medications4
– Side effects5
• Patient-related
– Concern about adverse effects3
– Suboptimal adherence to medication or lifestyle measures1
– Underuse of medications as a result of costs4 or complexity
of therapy1
. Leeuw IH. Diabetologia. 2003;46 Suppl 1:M44-50; 3. McDonald HP
1. Blonde L. Clin Cornerstone. 2005;7(Suppl 3):S6–S17; 2. Van Gaal LF, De
et al. JAMA. 2002;288(22):2868-79; 4. Piette JD et al. Diabetes Care. 2004;27(2):384-91; 5. Wabe NT et al. N Am J Med Sci. 2011;3(9):418-23.
Clinical Inertia and A1C
Median Time (Years) to Treatment Intensification for
Patients on One Oral Antihyperglycemic Agent and
with Various A1C Levels
3.5
Time (years)
3.0
2.9
2.5
1.9
2.0
1.6
1.5
1.0
0.5
0.0
≥7.0% (n = 35,988)
≥7.5% (n = 31,375)
A1C Cutoff
Khunti K et al. Diabetes Care. 2013;36(11):3411-7.
≥8.0% (n = 25,096)
Adherence to Antihyperglycemic
Therapy in Quebec
Total oral
antihyperglycemic
agents
Metformin
Secretagogue
Other
Stopped
at 1 year
Persistent but
non-adherent
at 1 year
Persistent and
adherent
at 1 year
20.7%
17.4%
61.9%
19.9%
25.6%
17.7%
17.7%
62.4%
56.7%
20.0%
13.4%
66.6%
Note: Individuals with a medication possession ratio (MPR) ≥80% for oral antihyperglycemic agents or insulin were deemed adherent; those having a
prescription filled for antihyperglycemic agents during the period leading up to the 1-year anniversary of their first claim were considered to be
persistent with their antihyperglycemic therapy.
Adapted from: Guénette L et al. Diabetes Metab. 2013 ;39(3):250-7.
Association between A1C and Adherence,
Adjusted for Baseline A1C and Oral
Antihyperglycemic Agent Regimen
8.8
8.4
8.0
Adjusted A1C
7.6
7.2
6.8
6.4
6.0
5.6
5.2
Every 10% ↑ in adherence is associated
with 0.1 % ↓ in A1C
4.8
4.4
4.0
0
10
20
30
40
50
60
Adherence (%)
Rozenfeld Y et al. Am J Manag Care. 2008;14(2):71-5.
70
80
90
100
Impact of Treatment Non-adherence on Mortality
in People with Type 2 Diabetes Treated with
Oral Antihyperglycemic Agents and Insulin
Non-adherence is associated with an increased risk of total mortality
70
P<0.001 vs. adherent
Adjusted increase in all-cause
mortality (%)
P=0.003 vs. adherent
60
61%
58%
Risk increase
50
40
30
P=0.007 vs. adherent
20
16%
10
0
Medication
non-adherence
Clinic non-attendance
Clinic non-attendance
(1–2 missed appointments) (>2 missed appointments)
UKGP records of patients with type 2 diabetes mellitus patients (n=15984).
Among those who were medication adherent, there was a significant (P <0.001) monotonic increase in mortality as nonattendance increased; among those who were
medication non-adherent, there was no significant difference in mortality as nonattendance increased (P = 0.489).
Adapted from Currie CJ et al. Diabetes Care. 2012;35(6):1279-84.
• In your opinion, how are
healthcare costs related to chronic
disease affected by medication
adherence?
Lack of Adherence in Chronic Diseases
Increases Healthcare Costs
For every 10% decrease in adherence:
• ↑ 1.2% in hospitalizations and ER visits (p<0.05)1
• ↑ 6.9% in hospitalizations (p < 0.05)2
• ↑ 5.1 % in ER visits (p < 0.05)2
• ↑ 8.6% in annual total healthcare costs (p < 0.001)3
• Cost of poor adherence in USA: $ 5 billion annually1
1. Jha AK et al. Health Aff . 2012;31(8):1836-46; 2. Shenolikar RA, Balkrishnan R. Diabetes Care. 2008;31(2):e5; 3. Salas M et al. Value Health.
2009;12(6):915-22.
Sarah
AGE: 69
Medical History/Previous Medical Records
BP: 125/78 mmHg
• Controlled hypertension and dyslipidemia
BMI: 33.3 kg/m2
Current Medications
• Ramipril 10 mg qd
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
• T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months of
lifestyle management
– Dose increased to 1000 mg bid 6 months
ago
– Gliclazide initiated 3 months ago at last visit
when A1C was 7.5%
Current Laboratory Results
• A1C: 7.5%
• LDL-C: 1.9 mmol/L
• eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• How would you determine if
non-adherence is the underlying
reason for Sarah’s elevated A1C?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
Medical History/Previous Medical Records
• Ramipril 10 mg qd
•
•
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
– Gliclazide initiated 3 months ago at last visit when A1C
was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• What questions might you ask?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
Medical History/Previous Medical Records
• Ramipril 10 mg qd
•
•
• Rosuvastatin 20 mg qd
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
– Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
– Gliclazide initiated 3 months ago at last visit when A1C
was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Morisky 4-item Medication
Adherence Scale
The 4-Item Morisky Scale
Have you ever forgotten to take your diabetes medicine?
Yes
No
At times, are you not careful about taking your diabetes
medicine?
Yes
No
When you feel better, do you sometimes stop taking your
diabetes medicine?
Yes
No
At times, if you feel worse when you take your diabetes
medicine, do you stop taking it?
Yes
No
No = 0
Yes = 1
Total score 0 = high adherence
Total score of 1 to 2 = medium adherence
Total score of 3 to 4 = low adherence
Adapted from: Morisky DE, Green LW, Levine DM. Medical Care. 1986;24(1):67-74.
Assessing Adherence Predicts
A1C Levels
• The 4-item Morisky scale predicts A1C
– Are you forgetful?
– Careless at times?
– Sometimes stop taking medication when feeling
better?
– Sometimes stop taking medication when feeling
worse?
• Each 1-unit increase in total score raises A1C by 0.16%,
6 months later
• Baseline endorsement of forgetting medication raises A1C
by 0.43% 6 months later (P=0.005)
Aikens JE, Piette JD. Diabet Med. 2013; 30: 338-44.
Results of a 2014 Survey on Adherence
Using the ‘Short’ Morisky Scale
Yes
No
0
n = 250 Canadian
specialists in
diabetes
Ontario:
Quebec:
Atlantic:
Prairies:
West:
40%
24%
9%
12%
15%
English: 86%
French: 14%
Forget to take
Careless at times
Stop when feeling
better
Stop when feeling
worse
Results from a 2014 survey by J-F Yale, Department of Medicine, McGill University.
No answer
50
100
Sarah took the Morisky
questionnaire
Let’s see her results
Sarah
Results of 4-Item Morisky Scale
Score
Have you ever forgotten to take your diabetes
medicine?
Yes
1
At times are you not careful about taking your
diabetes medicine?
No
0
When you feel better, do you sometimes stop
taking your diabetes medicine?
No
0
At times, if you feel worse when you take your
diabetes medicine, do you stop taking it?
Yes
1
No = 0
Yes = 1
Total score 0 = high adherence
Total score of 1 to 2 = medium adherence
Total score of 3 to 4 = low adherence
Adapted from: Morisky DE, Green LW, Levine DM. Medical Care. 1986;24(1):67-74.
Sarah
• Given Sarah’s responses, what
factors might be contributing to
her non-adherence?
Sarah
• What might you say to Sarah in
your consultation at this point?
Factors Affecting Adherence
to Medication (WHO)
• Health System
• Condition
• Patient
• Therapy
• Socio-economic
Adapted from the World Health Organization (WHO). Adherence to Long-term Therapies. 2003.
Effect of Medication Dosing
Frequency on Adherence in T2DM –
Systemic Review of 4 Studies
Adherence Range (%)
100%
79% to 94%
75%
38% to 67%
50%
25%
0%
QD
Dosing
BID or TID
Study selection criteria included the use of medication event monitoring systems (MEMS) to measure adherence.
BID = twice daily; QD = daily; T2DM = type 2 diabetes mellitus
Adapted from Saini SD et al. Am J Manag Care. 2009;15(6):e22-33.
Dosing Frequency and Medication
Adherence in Chronic Disease –
Meta-Analysis 51 Studies
Taking
Adherence
0%
N = 1259 1326
57
Regimen
Adherence
826
321
86
Timing
Adherence
650
343 109
-7%
-10%
Adjusted differences
in adherence rates
(%) were all
statistically
significant compared
with once-daily
regimens
-13%
-14%
-19%
-20%
-25%
-23%
-27%
BID
TID
QID
-30%
-39%
-40%
-50%
-60%
For once-daily regimens: 1n=2006, 2n=2118, 3n=936
BID = twice-daily dosing; QID = four times daily dosing; TID = thrice-daily dosing
Adapted from Coleman CI et al. J Manag Care Pharm. 2012;18(7):527-39.
-54%
Impact of Fixed-Dose
Combinations on A1C
Selected articles were limited to studies that compared equivalent drug
components within fixed-dosed combinations and coadministered dual therapy
Study
Mean difference
of A1C (95% CI) Weight (%)
Blonde L et al., 2003
-0.53% (-0.80,-0.26)
28.0%
Thayer S et al., 2010
-0.31% (-0.66,-0.04)
22.7%
Thayer S et al., 2010
-0.45% (-0.77,-0.13)
24.7%
Blonde L et al., 2003
-0.60% (-0.97,-0.23)
21.4%
Raptis et al., 1990
-2.30% (-3.65,-1.00)
3.2%
Overall
-0.53% (-0.78,-0.28)
100%
-4.0 -3.5 -3.0
-2.5 -2.0 -1.5 -1.0 -0.5
0.0
0.5
Mean difference in A1C (FDC-Dual)
Meta-analysis:
10 articles chosen
out of 152
Favors FDC
Han S et al. Curr Med Res Opin. 2012 ;28(6):969-77.
Trial
Medication Possession Number of
Ratio (95% CI)
Studies
FDC vs. Dual
Mono to FDC vs. Dual
+8.6% (1.6-15.6)
+7.7% (5.7-9.6)
5
4
Dual to FDC vs. Dual
+5.0% (3.1-6.8)
3
Impact of Fixed-Dose Combinations on
Self-Reported Adherence and
Cardiovascular Risk Factors
Fixed-dose
Combination (n=256)
Usual Care
(n=257)
Treatment Effect*
(95% CI)
P-value
208 (81)
119 (46)
1.75 (1.52−2.03)
<0.001
Systolic BP
−4.5 (21.0)
−2.3 (18.1)
−2.2 (−5.6−1.2)
0.21
Diastolic BP
−2.1 (11.8)
−0.9 (11.2)
−1.2 (−3.2−0.8)
0.22
−0.20 (0.73)
−0.15 (0.72)
−0.05 (−0.17−0.08)
0.46
Number (%) with self reported
current use of antiplatelet,
statin, and ≥2 BP lowering
drugs at 12 months
Mean (SD) change in BP over
12 months (mmHg):
Mean (SD) change in LDL-C
over 12 months (mmol/L)
BP = blood pressure
*Relative risks for binary outcomes or difference in change between baseline and 12 months or end of follow-up for continuous outcomes; all results
unadjusted.
Selak V et al. BMJ. 2014;348:g3318.
90.0
100.0
80.0
Satisfaction
90.0
80.0
70.0
70.0
60.0
60.0
50.0
50.0
40.0
40.0
30.0
Non-Adherence
30.0
20.0
20.0
10.0
10.0
0.0
0.0
None
One
Two
Three
Percentage Non-adherent
Diabetes Satisfaction Score
Side Effects and Adherence
Side Effects Reported by
Patients with Type 2 Diabetes
N=2074 questionnaires
Hypoglycemia
Constipation/diarrhea
Nausea and Vomiting
Loss of appetite
Headaches
Weight gain
Water retention
57%
28%
7.3%
5.7%
25.6%
22.9%
21%
Four or more
Number of tolerability issues
22% had 1 side effect, 19.9% had 2, 14.1% had 3, and 15.7% had 4 or more
71.7% had at least one side effect in past 2 weeks
For every additional side effect, non-adherence rose 28% (p<0.01)
Pollack MF et al. Diabetes Res Clin Pract. 2010;87(2):204-10.
Socio-economic Factors Affecting
Adherence to Medication
IMPACT OF MEDICATION COST
ON ADHERENCE
Use of essential drugs
Use of less essential drugs
0
Percentage (%)
• High
medication
costs
• Poor social
support
• Low health
literacy
-5
-10
-9.12
-15.14
-14.4
-15
-20
-22.39
-25
Elderly
Wang TY et al. BMC Health Serv Res. 2013;13:442
Welfare recipients
Tell us what you think
What data were most surprising?
Sarah
Medical
History/Previous Medical Records
Upon Further
Questioning…
• Controlled
125/78
mmHg she initially
•BP:
Sarah
reveals
took thehypertension
gliclazideand
asdyslipidemia
prescribed
• T2DM diagnosed
1 yearshe
ago has
BMI:
but33.3
did kg/m
not 2renew the prescription
because
– Metformin 500 mg bid initiated after 3 months
experienced
8 hypoglycemic
episodes and some
Current
Medications
of lifestyle management
gastrointestinal
upset.
• Ramipril
10 mg qd
– Dose increased to 1000 mg bid 6 months
AGE: 69
20 mg qd
•• Rosuvastatin
She did not
want to bring it up with you because she
– Gliclazide initiated 3 months ago at last visit
• Metformin 1000 mg bid
considers herself a “good patient”
and
when A1C
waswas
7.5% embarrassed.
ago
• Gliclazide MR 60 mg qd
Current Laboratory Results
• A1C: 7.5%
• LDL-C: 1.9 mmol/L
• eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• How does this new information change
your interpretation of the fact that
Sarah’s A1C level has not changed
since the last visit?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
• Ramipril 10 mg qd
• Rosuvastatin 20 mg qd
Medical History/Previous Medical Records
•
•
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
–
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
–
Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
Gliclazide initiated 3 months ago at last visit when A1C was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Sarah
• How does this new information affect
your clinical decision making?
AGE: 69
BP: 125/78 mmHg
BMI: 33.3 kg/m2
Current Medications
• Ramipril 10 mg qd
• Rosuvastatin 20 mg qd
Medical History/Previous Medical Records
•
•
Controlled hypertension and dyslipidemia
T2DM diagnosed 1 year ago
–
• Metformin 1000 mg bid
• Gliclazide MR 60 mg qd
–
Metformin 500 mg bid initiated after 3 months of lifestyle
management
– Dose increased to 1000 mg bid 6 months ago
Gliclazide initiated 3 months ago at last visit when A1C was 7.5%
Current Laboratory Results
•
•
•
A1C: 7.5%
LDL-C: 1.9 mmol/L
eGFR: 63 mL/min/1.73 m2
bid = twice daily;BMI=body-mass index; eGFR= estimated glomerular filtration rate;
qd = once daily; T2DM=type 2 diabetes mellitus;
Evidence-Based Strategies to
Enhance Adherence
What strategies could you
integrate into your practice?
Strategies to Enhance Adherence
Assess adherence
Empowerment
Education
Reduce side effects
Simplify therapy
1. Brown MT, Bussell JK. Mayo Clin Proc. 2011;86(4):304-14. 2.WHO. Behavioural mechanisms explaining adherence. 2003.
Strategies to Enhance Adherence
Assess
adherence
Empowerment
Education
Reduce side
effects
Simplify
therapy
Assess adherence to current medications
• Periodically
• In a non-judgmental manner
When a change in therapy is indicated
• Explain why
• Discuss available options and their advantages and disadvantages
• Allow the patient to participate in the decision making
When initiating a drug
• Explain the expected benefits
• Provide instructions on dosage and administration
• Describe the expected side effects and ways to reduce their frequency
Choose medications with
• Lowest rates of side effects with the same efficacy
When feasible, simplify regimen by using
• Once-daily agents
• Fixed-dose combinations
• Packaging (pill boxes or blister packs) to simplify the regimen
1. Brown MT, Bussell JK. Mayo Clin Proc. 2011;86(4):304-314. 2. WHO. Behavioural mechanisms explaining adherence. 2003.
Strategies to Assess Adherence
Assess
adherence
Periodically assess adherence to current medications in a
non-judgmental way.
Empowerment
Showing empathy to potentially non-adherent patients will
encourage forthcoming responses.
Education
Reduce side
effects
Simplify
therapy
There is a vital need to reconcile what a patient is actually
taking with the prescribed regimen and to understand why
there is a difference.
•
Patient is non-adherent
•
Physician ignores
•
Poor results = increased medication
•
What is the patient to do?
•
Ignore the new drug = greater gap
•
Take the new drug = risk of side effects and overtreatment
1. Brown, M.T., Bussell, J.K., Mayo Clin Proc, 86(4), 2011, p. 304-314; DOI :10.4065/mcp.2010.0575.
2. OMS, Behavioural mechanisms explaining adherence, 2003.
Strategies to Empower Patients
Assess
adherence
Empowerment
Education
When a change in therapy is indicated, explain why, discuss
the therapeutic options available, their advantages and
disadvantages, and allow the patient to participate in the
decision making.
Example:
• 55-year-old man on metformin, A1C=7.9%
• Secretagogue = lowest price, established long-term
safety, can cause hypoglycemia and weight gain
Reduce side
effects
Simplify
therapy
• DPP-4 inhibitor = no side effects, no hypoglycemia or
weight gain, higher price
• GLP-1R agonist = greater efficacy, promotes weight loss,
no hypoglycemia, given by injection, GI side effects,
highest cost
1. Brown, M.T., Bussell, J.K., Mayo Clin Proc, 86(4), 2011, p. 304-314; DOI :10.4065/mcp.2010.0575.
2. OMS, Behavioural mechanisms explaining adherence, 2003.
Strategies to Educate Patients
Assess
adherence
Empowerment
Education
Reduce side
effects
Simplify
therapy
When initiating a drug, explain the expected benefits,
provide instructions on dosage and administration, and
describe the expected side effects and ways to reduce their
frequency.
Strategies to Reduce Side Effects
Assess
adherence
Empowerment
Education
Reduce side
effects
Choose medications with the lowest rates of side effects for
the same efficacy.
Simplify
therapy
Harper, W., Clement, M., Goldenberg, R. et coll., Canadian Journal of Diabetes, 37, 2013, p. S61-S68;
Overview of Side Effects of
Antihyperglycemic Agents
2013 CDA Guidelines: Add an agent best suited to the individual
(agents listed in alphabetical order)1
Class
Relative A1C
lowering
↓
Hypoglycemia
Rare
Weight
↓↓
↓↓ to ↓↓↓
↓↓↓
Rare
Rare
Yes
Neutral to ↓
GI side effects
↓↓
↑↑
No dose ceiling, flexible regimens
↓↓
↓↓
Yes
Yes
↑
↑
Less hypoglycemia in context of missed
meals but usually requires tid to qid
dosing Gliclazide and glimeride
associated with less hypoglycemia than
glyburide
$$
$
TZDs
↓↓
Rare
↑↑
$$
Weight loss agent (orlistat)
↓
None
↓
CHF, edema, fracture, rare bladder
cancer (pioglitazone), CV controversy
(rosiglitazone), 6-12 weeks required for
maximal effect
GI side effects
Alpha-glucosidase inhibitor
(acarbose)
Incretin agents
DPP-4 inhibitors
GLP-1 receptor agonists
Insulin
Insulin secretagogues
Meglitinides
Sulfonylureas
Other therapeutic considerations
Neutral to ↓ Improved postprandial control
GI side effects
Cost
$$
$$$
$$$
$-$$$$
$$$
1. Adapted from Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37, S1-S212.
A new class, SGLT-2 inhibitors, have entered the market since the CDA guidelines publication in 2013.
The features below do NOT represent the views of the CDA 2013 guidelines.
SGLT-2 inhibitors2,3
↓↓ to ↓↓↓
Rare
2. Rosentock J, et al. Diabetes Care. 2012; 35(6): 1232-1238;
3. Mikhail, N. Curr Drug Saf, 2014 Jan 19.
↓↓
Increased frequency of genital mycotic
infections
Othostatic/postural hypotension
Increased risk of hypoglycemia if used in
conjunction with insulin or sulfonureas
$$$
Strategies to Simplify Therapy
Assess When feasible use:
adherence
• Once-daily agents
• Fixed-dose combinations
Empowerment
• Convenient packaging (pill boxes or blister packs)
Education
Reminders to take medications can also be useful:
• Alarm or SmartPhone reminders
Reduce side
• Taking medication in conjunction with a regular activity
effects
(e.g., brushing teeth)
Simplify therapy
Screen for cognitive impairment starting at age 70 years using
simple tests like the Mini-Cog.
Borson, S. et coll., Int J Geriatr Psychiatry, 15(11), 2000, p. 1021-1027.
Factors Affecting
Adherence to Medication (WHO)
Complexity of regimen: pill burden
Predictors of poor adherence:
Predictor
Value
Number of medications
≥5
Number of daily doses
≥12
Number of prescribing physicians
≥3
Changes in medications in the last year
≥4
Number of diseases treated
≥3
Examples of pill burden:
Therapy
Number of Different Medications
Number of Pills
Frequently used triple therapy
3
7
Hypertension
3
3
Lipids
1
1
ASA
1
1
Adapted from the World Health Organization (WHO). Behavioural mechanisms explaining adherence. 2003.
Mini-Cog Test
1. Instruct the patient to remember three
unrelated words. For example:
– Blue
– Apple
– Train
2. Instruct the patient to draw the face of a
clock, and then to place the arms of the
clock to indicate a specific time (for
example,10 minutes past 11).
Borson S. et al. Int J Geriatr Psychiatry. 2000;15(11):1021-7.
Example of Mini-Cog Test
Outcome
Mini-Cog Test
3. Ask the patient to repeat the 3 words
previously stated.
Borson S. et al. Int J Geriatr Psychiatry. 2000;15(11):1021-7.
Mini-Cog Interpretation
• 0 words retained = cognitive defect
• 1 or 2 words retained: look at the clock
– Abnormal clock = cognitive defect
– Normal clock = no cognitive defect
• 3 words retained = no cognitive defect, no need to
look at the clock
Borson S. et al. Int J Geriatr Psychiatry. 2000;15(11):1021-7.
Currently Available Oral Fixed Dose
Combination for T2DM Patients
in Canada*
Dose
Agent
+
Metformin
Metformin
type
Second
agent
IR
Rosiglitazon
e
Avandamet
2 or 4 mg
500 or 1000
mg
1 tab BID
IR
Sitagliptin
Janumet
50 mg
500 or 850
or 1000 mg
1 tab BID
XR
Sitagliptin
Janumet XR
50 mg
1000 mg
2 tabs OD
IR
Linagliptin
Jentadueto
2.5 mg
500 or 850
or 1000 mg
1 tab BID
IR
Saxagliptin
Komboglyze
2.5 mg
500 or 850
or 1000 mg
1 tab BID
Brand name
*Agents presented in alphabetical order by brand name
BID = twice daily; IR = immediate release; OD = once daily; XR = extended release
Adapted from Health Canada Drug Product Database, Accessed May 24, 2014.
Frequency
DPP-4 Inhibitors and Metformin Target
the Metabolic Defects of Type 2 Diabetes
DPP-4 inhibitors
improve beta-cell
function and
increase insulin
synthesis and
release.1
Beta-cell
Dysfunction
DPP-4 inhibitors reduce HGO
through suppression of glucagon
secretion from alpha cells.
Hepatic Glucose
Overproduction
(HGO)
Insulin
Resistance
Metformin has
insulin-sensitizing
properties.2–4
(Liver > Muscle)
Metformin decreases HGO
by targeting the liver to
decrease gluconeogenesis
and glycogenolysis.3
DPP-4 = didpetidyl peptidase-4
1. Aschner P et al. Diabetes Care. 2006;29(12):2632-7; 2. Abbasi F et al. Diabetes Care. 1998;21(8):1301-5; 3. Kirpichnikov D et al. Ann Intern Med.
2002;137(1):25-33; 4. Zhou G et al. J Clin Invest. 2001;108(8):1167-74.
Adherence by Patients Switched
from Metformin IR to Metformin XL
Adherence (%) Before and After
Switch from Standard Metformin
Adherence (%) Overall Population
90
80
70
60
90
*p = 0.0026
80%
72%
*p = 0.0001
85
80
81%
75
50
70
40
65
30
20
60
10
55
0
50
Metformin IR (n=10 019) Metformin XL (n=80)
62%
Metformin IR (n=40)
Metformin XL (n=40)
Retrospective observational study of patients with T2DM from a single diabetes clinic in Scotland.
Clinical value of retrospective data is not as robust as data from
prospective randomized controlled trials.
IR = immediate release; T2DM = type 2 diabetes mellitus; XR = extended release
MET XL = GLUCOPHAGE SR ©
Adapted from Donnelly LA et al. Diabetes Obes Metab. 2009;11(4):338-42.
The ODYSSEE Study
• Sulfonylurea and DPP-4 inhibitors are usually
prescribed in combination with metformin
• ODYSSEE was:
– A prospective, real-world, observational study
– Conducted in France in primary care practices
• Comparison of the duration of maintenance
treatment without modification between:
– Metformin + sitagliptin (MetSita, 1874 patients)
– Metformin + sulfonylurea (MetSU, 733 patients)
• Group assignments were based on physician choice.
• Patients were followed up for up to 3 years
DPP-4 = didpetidyl peptidase-4
P. Valensi et al. ADA abstract- 2014-LBA-5979
ODYSSEE Study:
Treatment Maintenance Duration
Probability for maintenance of
initial dual therapy
Product-Limit Survival Estimates
with Number of Subjects at Risk and 95% Hall-Wellner Bands
1.0
Logrank p<0.0001
0.8
MetSita
0.6
MetSU
0.4
0.2
0.0
1 1874 1293 1071 890
2 733 441 345 269
0
10
20
766
229
666
203
30
405
113
45
14
40
0
0
50
Maintenance duration (months) until treatment modification
• Median treatment maintenance durations for study treatments were:
– Metformin + sitagliptin (MetSita group) : 43.2 months [95%CI: 41.4 – NE]
– Metformin + sulfonylurea (MetSU group): 20.2 months [95%CI: 17.0 – 25.1]
P. Valensi et al. ADA abstract- 2014-LBA-5979
Mean A1C (%)
ODYSSEE Study:
Change of A1C Over Time
Changes in A1C level up to the modification
of the initial dual therapy
7.6
Group: p=0.024
Time: p<0.001
7.4
Interaction: p=0.014
MetSU
7.2
7.0
MetSita
6.8
6.6
6.4
N=1735 N=1263 N=1089 N=921 N=793
N=678 N=490 N=370 N=286 N=245
Inclusion
6
12
18
24
30
N=688 N=592
N=206 N=190
36
Follow-up duration (in months)
A reduction in A1C level (about -0.6%) was observed during the first 6 months of treatment in both
study arms and was maintained until the end of the observation period.
P. Valensi et al. ADA abstract- 2014-LBA-5979
Occurrence of asymptomatic
hypoglycemia episode (%)
ODYSSEE Study:
Hypoglycemia and Safety
25
21%
20
15
9.7%
10
5
0
MetSita Group
N=1874
MetSU Group
N=733
• Overall rates of adverse events (AEs) were:
– MetSita Group: 130 (6.9%) patients reported a total of 159 AEs
– MetSu Group: 58 (7.9%) patients reported a total of 79 AEs
• Rates of adverse events potentially related to treatment were:
– MetSita Group: 52 (2.8%) patients reported a total of 60 AEs
– MetSu Group: 20 (2.7%) patients reported a total of 24 AEs
P. Valensi et al. ADA abstract- 2014-LBA-5979
• What strategies could be used
to help Sarah reach her A1C
target?
A1C = glycosylated hemoglobin
Reflection on Your Practice
Describe the strategies you are
most likely to use in your practice
to increase patient adherence.
Reflection on Your Practice
What do clinicians need to help
facilitate adoption of strategies to
increase patient adherence?
Sarah
AGE: 69
Medical History and Medical Records
BP: 125/78 mmHg
• Controlled hypertension and dyslipidemia
• T2DM diagnosed 1 year ago
BMI: 33.3 kg/m2
Previous Medications
•
•
•
•
Ramipril 10 mg qd
Rosuvastatin 20 mg qd
Metformin 1000 mg bid
Gliclazide MR 60 mg qd
Newly Adjusted Medications
• Ramipril 10 mg qd
• Rosuvastatin 20 mg qd
• Metformin/Sitagliptin XR
1000/50 mg 2 tabs qd
– Metformin 500 mg bid initiated after 3 months of
lifestyle management
– Dose increased to 1000 mg bid 6 months ago
– Gliclazide initiated 3 months ago at last visit
when A1C was 7.5%
Previous Laboratory Results
• A1C: 7.5%
• LDL-C: 1.9 mmol/L
• eGFR: 63 mL/min/1.73 m2
Benefits
• Reduction in number of pills per day from 8 to 4
• Cessation of hypoglycemic episodes
• Better tolerance of metformin
Roundtable Feedback
What are the key insights you
gained in this session?
Key Points
• Non-adherence to medication is a very frequent
problem that is too often ignored.
• It is important to routinely assess adherence to
medications before adding a new drug.
• If non-adherence seems to be present, assess
what factors may be enhancing the problem.
• Educate patients and, if required, make changes
to medications to improve adherence.