Breaking the Cycle: Using Incretin-Based Therapies to Overcome Clinical Inertia in Type 2 Diabetes

Thursday, April 23, 2009 6:00 AM - 8:00 AM Philadelphia Marriott Downtown

Clinical Inertia: Challenges in Managing Type 2 Diabetes in a Primary Care Setting

Scott V. Joy, MD, FACP Associate Professor of Medicine Medical Director, Duke Primary Care at Pickett Road Duke University Health System Durham, North Carolina

Case Study: Surita Patel

Surita’s Medication List

• 48-year-old female of Indian descent • Type 2 diabetes diagnosed 7 years ago • Obese

• Medications reconciled and entered into electronic prescribing system:

– Weight = 176 lbs – BMI = 31.2 kg/m22

• A1C – Current = 8.0% – Previous (18 months ago) = 7.9%

Additional Issues for Surita • Not at goal with: – Weight (176 lbs, 31.2 kg/m2) – Blood pressure (144/92 mm Hg) – Lipids (LDL = 132 mg/dL)

• Missing appointments (≈ 12-18 months between appointments) • Does not have SMBG results • Feels she is getting inconsistent information from different HCPs in the practice • Admits to not taking her medication regularly

– Metformin: 1000 mg, by mouth, twice daily – Glipizide: 5 mg, by mouth, once daily – Lisinopril: 20 mg, by mouth, once daily – Aspirin: 81 mg, by mouth, once daily – Simvastatin: 40 mg, by mouth, once daily

• Metformin and glipizide doses have not been changed since previous visit (18 months ago)

Which of the following options do you believe would most improve Surita’s diabetes management? 1. Assess barriers with the patient to determine reasons for her nonadherence with medication and lifestyle recommendations 2. Recommend consultation/sessions with diabetes educator 3. Screen for depression 4. Intensify glycemic control therapy 5. Transfer patient to another practice to improve your practice’s pay-for-performance scores 6. Other

Loss of β-cell Function Begins Long Before the Diagnosis of Type 2 Diabetes TZDs may preserve β-cell function*, slow progression from IGT to diabetes

100

Incretin-based therapies may preserve βcell mass*

-Cell Function (%)

Progressive, Multifactorial Pathophysiology Sets the Stage for Clinical Inertia in Type 2 Diabetes

75

50

Postprandial Hyperglycemia

25

0 -12 -10 *Based on mathematical and/or animal models.

Many, if not all, are consequences of increased insulin insulin resistance.  insulin secretion   incretin effect

  lipolysis lipolysis

  glucagon glucagon secretion secretion

Hyperglycemia

  hepatic glucose glucose production

 glucose glucose reabsorption

uptake Neurotransmitter  glucose uptake dysfunction

-6

Type 2 Diabetes Phase I

-2

0

Type 2 Diabetes Phase II

2

Type 2 Diabetes Phase III

6

10

Insulin needed when β-cell function is lost

14

Years From Diagnosis Lebovitz HE. Diabetes Rev. 1999;7:139-153. DeFronzo R. 2008 Banting Memorial Lecture. Available at: http://webcasts.prous.com/netadmin/webcast_viewer/Preview.aspx?type=0&lid=3831.

Ability to Achieve Glycemic Control With Monotherapy Decreases Over Time % Achieving A1C < 7%

“Ominous Octet” Contributes to Hyperglycemia

Secretagogues lose efficacy as β-cell function declines

IGT

100 80 Diet SU MET* Insulin

60 40 20 0 3

6

9

Disease Duration (years) DeFronzo R. 2008 Banting Memorial Lecture. Available at: http://webcasts.prous.com/netadmin/webcast_viewer/Preview.aspx?type=0&lid=3831.

Physician Behaviors Contribute to Clinical Inertia

*Limited to overweight patients.

Turner RC, et al. JAMA. 1999;281:2005-2012.

Definition of Clinical Inertia • General – Recognition of the problem, but failure to act – Failure to initiate or intensify therapy when indicated

• Functional* – Proportion of patients with elevated measures of glycemic control who do not receive therapeutic intensification

*Definition *Definition specific specific to to glycemic glycemic control control in in patients patients with with type type 22 diabetes diabetes and and aa potential potential measure measure of of healthcare healthcare quality. quality. Phillips LS, et al. Ann Intern Med. 2001;135:825-834. Berlowitz DR, et al. Health Serv Res. 2005;40(6 pt 1):1854-1861.

American Diabetes Association Guidelines: Therapeutic Intensification for Glycemic Control • Statement on recent trial results (ACCORD, ADVANCE, VADT) – Glycemic target still A1C < 7% – Emphasis on individualized therapy • Initiate or change therapy at A1C ≥ 7% • More or less stringent goals appropriate for some patients – More stringent: short diabetes duration, long life expectancy, no significant cardiovascular disease – Less stringent: hypoglycemia, advanced complications, extensive comorbid conditions, long-standing diabetes with difficulty achieving treatment goals Skyler JS, et al. Diabetes Care. 2009;32:187-192. Nathan DM, et al. Diabetes Care. 2009;32:193-203. American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S13-S61.

Clinical Inertia is Common in Type 2 Diabetes Studies reveal that therapy is intensified for < 50% of patients with A1C above target. Intensification Rate (%)

(N = 2065)

Schmittdiel et al (N = 64,821)

Shah et al (primary care) (N = 585)

Shah et al (specialist care) (N = 585)

< 7.0

33

≤ 7.0

47

≤ 8.0

37

≤ 8.0

45

5.4 5.4

0 0 1997 1997

2005 2005

Time/Visit Time/Visit (min) (min)

A little more time per visit... *

25 25 20 20

18 18

20.9 20.9

4.5

Time/Item (min)

Items/Visit (n) (n) Items/Visit

5 5

Less time per item!

*

7.1 7.1

4.4

4

• Intensify every 2 to 3 months until glycemic goals are met

AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):3-68. ACE/AACE Diabetes Road Map Task Force. Available at: http://www.aace.com/meetings/consensus/odimplementation/roadmap.pdf.

Missed Intensification Opportunities Result in Poorer Glucose Control *

1.4

1

*

0.8

0.5

0

More Clinical Items and Less Time During Primary Care Visits More items per visit...

• Initiate monotherapy at A1C of 6% to 7% or combination therapy at A1C of 7% to 8%

N N= = 133 133 (13 (13 not not appropriately appropriately intensified) intensified) 24-month 24-month study study

Grant R, et al. Diabetes Care. 2007;30:807-812. Schmittdiel JA, et al. J Intern Med. 2008;23:588-594. Shah B, et al. Diabetes Care. 2005;28:600-606.

10 10

• A1C goal ≤ 6.5%

1.5

A1C Target (%)

Grant et al

Therapeutic Intensification for Glycemic Control

A1C Difference vs Intensified Group (%)

Study

American Association of Clinical Endocrinologists Guidelines:

* 3.8

1 to 2

3 or more

Quarters With No Intensification

*P < .001 for trend; † P < .001 vs no intensification. Similar trends observed for blood pressure and lipids.

Samuels TA, et al. J Gen Intern Med. 2008;23:1770-1777.

Clinical Inertia Physician Contributions • Lack of knowledge – Diabetes is a complex, progressive, multifactorial disease state – Multiple evidence-based practice guidelines – Multiple therapeutic options

• Burden of management tasks

3.5

15 15 1997 1997

2005 2005

* Significant change from 1997 to 2005.

1997

2005

Abbo ED, et al. J Gen Intern Med. 2008;23:2058-2065.

Joy SV. Diabetes Educ. 2008;34:54S-59S. Phillips LS, et al. Ann Intern Med. 2001;135:825-834.

As a provider, what is your biggest reason for clinical inertia in managing type 2 diabetes?

Patient Behaviors Contribute to Clinical Inertia

1. Lack of knowledge of clinical treatment guidelines and therapeutic goals 2. Lack of knowledge of medication indications and safety 3. Perception of poor patient acceptance of additional therapy 4. Lack of adequate time due to volume of patients required to support salary and staff 5. Poor access to diabetes education 6. Other

Factors Associated with First-Fill Adherence Rates for Diabetes Medications

Factors Associated with First-Fill Adherence Rates for Diabetes Medications Prescribed Prescribed Medication Medication

• N = 1132

(Reference: (Reference: Biguanide) Biguanide)

– Patients prescribed a diabetes medication for first time between 2002 and 2006 – Retrospective review of electronic health records and pharmacy claims

SU SU Insulin Insulin†† *,† OTHER OTHER*,†

Copay Copay ≤ ≤ $10 $10††

(Reference: (Reference: Copay Copay > > $10) $10)

• Primary outcome: Naïve prescription filled by patient within 30 days of prescription order date

A1C A1C ≥ ≥ 9% 9%††

(Reference: (Reference: A1C A1C < < 9%) 9%)

00

• Results – Overall first-fill adherence was 85% – Several factors associated with first-fill adherence Shah NR, et al. J Gen Intern Med. 2009;24:233-237.

11

22

33

66

First-fill First-fill adherence adherence not not associated associated with with age, age, sex, sex, or or comorbidity comorbidity score. score. *Includes *Includes initial initial prescription prescription with with > > 11 agent; agent; ††P < .05 vs reference; ‡‡OR > 1 indicates P < .05 vs reference; OR > 1 indicates greater greater likelihood likelihood of of prescription prescription fill. fill.

Clinical Inertia Patient Contributions

• Poor treatment adherence

• Poor understanding

Joy SV. Diabetes Educ. 2008;34:54S-59S. Rubin RR. Am J Med. 2005;118:27S-34S. Odegard PS, Gray SL. Diabetes Educ. 2008;34:692-697.

55

Odds Ratio (95% CI)‡

Clinical Inertia Patient Contributions – Regimen complexity – Lack of perception of treatment benefits – Adverse effects – Cost – Poor emotional well-being – Practical issues (remembering doses, reading labels, obtaining refills)

44

Shah NR, et al. J Gen Intern Med. 2009;24:233-237.

– Importance of self-management – Disease consequences – Therapeutic program and options

• Concerns regarding intensification – Injections – Side effects – Feelings of failure and guilt

Joy SV. Diabetes Educ. 2008;34:54S-59S.

Which strategy are you most likely to try first to improve patient medication adherence?

Patient and Physician Behaviors are Related Poor Medication Adherence Adherence Correlates Correlates With With Lower Lower Therapeutic Therapeutic Intensification Intensification

% of of Patients Patients Receiving Receiving % Therapeutic Intensification Intensification Therapeutic

N N= = 2065 2065 Mean Mean baseline baseline A1C A1C = = 9.4% 9.4%

40 35 30 25 20 15 10 5 0

PP < < .001 .001

Discuss Discuss importance importance of of adherence, adherence, benefits benefits of of therapy therapy using using motivational motivational techniques techniques

2. 2.

Adjust Adjust therapy therapy to to accommodate accommodate patient patient barriers barriers to to adherence adherence (side (side effects, effects, number number of of pills/doses, pills/doses, price, price, etc.) etc.)

3. 3.

Recommend Recommend strategies strategies to to improve improve adherence adherence (pill (pill reminder/organizer, reminder/organizer, mail mail order order refill, refill, medication medication assistance assistance

38 38

PP = = .001 .001

Medication Medication Adherence: Adherence:

32 32 23 23

1. 1.

27 27

90%

21 21

15 15

At At 6 6 Months Months

programs, programs, etc.) etc.)

At At 12 12 Months Months

Patients Patients with with type type 22 diabetes diabetes and and elevated elevated A1C A1C following following initiation initiation of of medication medication for for glycemic glycemic control. control.

4. 4.

Schedule Schedule longer longer and/or and/or more more frequent frequent office office visits visits

5. 5.

Schedule Schedule consultation consultation with with diabetes diabetes educator educator

6. 6.

Referral Referral to to an an endocrinologist endocrinologist

Grant R, et al. Diabetes Care. 2007;30:807-812.

Approaches to Overcoming Clinical Inertia Patient Behaviors • Proactive contact, surveillance, and reminders • Motivational techniques • Improve communication – Verify recall and comprehension regarding new information – Clarify treatment benefits • Minimize adverse effects – Discuss adverse effects – Adjust regimen • Simplify regimens • Methods to improve adherence (pill organizers, easily readable labels, memory systems, etc.) • Minimize cost Joy SV. Diabetes Educ. 2008;34:54S-59S.

Approaches to Overcoming Clinical Inertia: Clinical Operations

Rubin RR. Am J Med. 2005;118:27S-34S. Odegard PS, Gray SL. Diabetes Educ. 2008;34:692-697.

Three Interventions Improve Diabetes Care in a Primary Care Clinic

N N == 345 345 internal internal medicine medicine residents residents Feedback: Feedback: Individual Individual meeting meeting with with endocrinologist endocrinologist investigator investigator every every 22 weeks weeks Reminders: Reminders: ComputerComputergenerated, generated, patient-specific patient-specific flow flow sheet sheet and and recommendations recommendations Significant Significant Results: Results: Increased Increased intensification intensification for for feedback feedback groups groups vs vs reminders reminders only only and and control control Greater Greater A1C A1C improvements improvements for for feedback feedback ++ reminder reminder vs vs control control

Intensification per per Recommendations Recommendations (%) (%) Intensification

Performance Feedback Improves Treatment Intensification (IPCAAD Study)

•• 33 interventions interventions –– 30-minute appointments every 3 months –– Reminder telephone calls to patients

60

•• Appointment Appointment •• Bring Bring medications medications and and logbooks logbooks •• Arrange Arrange for for blood blood work work

50

40

Feedback + Reminders Feedback Only Reminders Only Control

30 Baseline

1

2

3

4

5

6

6-mo 6-mo Measurement Measurement Interval Interval

Ziemer DC, et al. Arch Intern Med. 2006;166:507-513. Phillips LS, et al. Diabetes Care. 2005;28:2352-2360.

–– Standardized diabetes care flow sheet from Canadian Diabetes Association •• 33 staff staff members members –– 1 physician –– 1 nurse –– 1 secretary •• 3-year 3-year study study

Lin D, et al. Can Fam Physician. 2007;53:73-77.

Three Interventions Improve Diabetes Care in a Primary Care Clinic Reference Group (n = 35)

Indicator

Intervention Group (n = 33)

Before

After

P-value

Before

After

P-value

Aspirin Use (%)*

24

45

.10

30†

70†

< .001

A1C (%)

7.7

7.4

.24

7.8

7.2

< .05

LDL-C (mmol/L)

121

115

.46

124

101

< .01

TC (mmol/L)/ HDL-C (mmol/L)

4.82

4.79

.95

4.76

4.21

< .01

Higher Rate of Medication Reinitiation

Time to Reinitiation (Days)

120 120

Reinitiation (%)

80 80

*

59.3 59.3 42.1 42.1

40 40 20 20

107.4 107.4

100 100 80 80

40 40 20 20 0 0 Intervention Intervention (n = 73 rx)

Control Control (n = 76 rx)

*Significantly different vs control.

Control Control (n = 32 rx)

Lawrence Lawrence DB, DB, et et al. al. Disease Disease Management Management.. 2008;11:141-144. 2008;11:141-144.

Open (Advanced) Access vs Standard Scheduling in Diabetes Management Process Outcomes

0.66 0.66

0.25 0.25

0.47 0.47

0.64 0.64

**

0.37 0.37

**

0.27 0.27

Mean Difference

Probability of of Testing Testing (Odds (Odds ratio) ratio) Probability

1.1 1.1

**

55 44 33 22 11 00

00 A1C A1C

6.4 6.4

66

11

0.5 0.5

*

77

Other

0.75 0.75

LDL LDL

Techniques Techniques for for medication medication behavior behavior change change Readiness Readiness to to change change Motivational Motivational interviewing interviewing Active Active listening listening Common Common barriers barriers to to adherence adherence Available Available resources resources Side Side effect effect management management Mail Mail order order benefits benefits Drug Drug assistance assistance programs programs Medication Medication organizers organizers Reminder Reminder systems systems

Urine Urine Microalbumin Microalbumin

*,† -0.12 -0.12

-0.2 -0.2

-1 -1 A1C A1C (%) (%)

SBP SBP (mm (mm Hg) Hg)

•• Comparison Comparison of of open open access access (same-day, (same-day, not not prebooked) prebooked) and and standard standard (prebooked) (prebooked) scheduling scheduling –– Retrospective study –– One year before and 1 year after open access implementation implementation

•• Outcome Outcome measures measures –– Processes of care (testing for A1C, LDL, urine microalbumin) –– Intermediate outcomes (A1C, LDL, SBP) SBP) –– Health care utilization (hospitalizations, (hospitalizations, ER/urgent ER/urgent care/primary care visits) *Eligibility based on income (< 200% Federal Poverty Level).

Subramanian U, et al. J Gen Intern Med. 2009;24:327-333.

• Elicit feedback on performance from partners and specialists • Implement patient-specific reminders • Utilize standardized flow sheets • Exploit clinical information systems for data management • Delegate responsibilities to other HCPs

LDL LDL (mg/dL) (mg/dL)

Test Test Type Type Significant Significant differences differences between between open open access access and and standard standard clinics clinics included included patient patient characteristics characteristics (age, (age, race, race, comorbidity comorbidity index, index, insulin insulin use, use, and and use use of of managed managed care) care) and and support support staff staff to to MD MD ratio. ratio. No No significant significant differences differences observed observed for for health health care care utilization. utilization.

*P < .05 for open access vs standard scheduling. †Clinically meaningful difference = 0.5%.

Lawrence DB, et al. Disease Management. 2008;11:141-144.

Overcoming Clinical Inertia in Your Practice

Intermediate Outcomes

African American

1.25 1.25

–– –– –– –– –– ––

•• N N == 4060 4060 –– Adult patients with type 2 diabetes –– Indiana University Medical Group-Primary Care –– Wishard Advantage Health Plan* participants

*

59.5 59.5

60 60

0 0

1.5 1.5

•• Care Care managers managers received received focused focused training training on: on:

Open (Advanced) Access vs Standard Scheduling in Diabetes Management

Shorter Time to Medication Reinitiation

100 100

Intervention Intervention (n = 123 rx)

•• Care Care managers managers informed informed of of nonadherence nonadherence

Lin D, et al. Can Fam Physician. 2007;53:73-77.

Targeted, Technology-Driven Disease Management Intervention

60 60

•• 155 155 patients patients who who were were nonadherent nonadherent to to medication medication identified identified through through pharmacy pharmacy claims claims data data

•• •• •• •• ••

Ophthalmology Ophthalmology referrals referrals also also significantly significantly increased increased in in the the intervention intervention group. group. No No significant significant changes changes in in pneumonia pneumonia or or influenza influenza vaccination vaccination rates, rates, systolic systolic blood blood pressure, pressure, diastolic diastolic blood blood pressure, pressure, or or weight. weight. *Indication of guideline adherence; †n = 30.

Targeted, Technology-Driven Disease Management Intervention

Subramanian U, et al. J Gen Intern Med. 2009;24:327-333.

Joy SV. Diabetes Educ. 2008;34:54S-59S. Phillips LS, et al. Diabetes Care. 2005;28:2352-2360. Ziemer DC, et al. Arch Intern Med. 2006;166:507-513. Lin D, et al. Can Fam Phys. 2007;53:73-77.

Learning Organization “…Organization that has developed the capacity to continuously adapt and change because all members take an active role in identifying and resolving work related issues…”

Case Study: Overcoming Clinical Inertia with Surita Patel – 3 months later • Actions following previous office visit – Surita was referred to a diabetes educator for information regarding self-management – Phone call reminders of appointments and necessary test results (including SMBG) were initiated

Robbins SP, DeCenzo DA. Fundamentals of Management: Essential Concepts and Applications. 5th ed. Upper Saddle River, NJ: Pearson Prentice Hall;2007.

Case Study: Overcoming Clinical Inertia with Surita Patel – 3 months later • This office visit – Surita kept her appointment and brought SMBG and lab results – Her current A1C is 7.7%, and she has lost 3 lbs – She is taking her medication regularly, although side effects are uncomfortable • Metformin causes occasional GI upset • Feels bloated with glipizide

– She is encouraged by her weight loss and would like to lose more

How would you modify Surita’s regimen to improve glycemic control, promote adherence, and address underlying diabetes pathophysiology? 1. Stop MET and SU due to side effects and initiate different therapy 2. Add TZD 3. Add GLP-1 agonist 4. Add DPP-4 inhibitor 5. Start insulin 6. Other