Connected for Life.

August 12, 2020

Overcoming Therapeutic

Inertia: What You Need to

Know

Kamlesh Khunti, PhD, MD

Stephen Brunton, MD

Thank You to Our Sponsors

2

Strategic Sponsors

Supporting Sponsors

About Today’s Presenters

Kamlesh Khunti, MD, PhD is a Professor of Primary Care Diabetes

and Vascular Medicine at the University of Leicester, UK and Co-

Director of the Leicester Diabetes Centre. Dr. Khunti is a leading

researcher on the impact of therapeutic inertia on diabetes care.

Stephen Brunton, MD is EVP for Education for the Primary Care

Education Consortium and an Adjunct Clinical Professor in the

Department of Pharmacy Practice at Roseman University of Health

Sciences. He currently serves as the Editor-in-Chief for Clinical

Diabetes, a journal of the American Diabetes Association.

Learning Objectives:

• Describe a working definition of therapeutic inertia

• Discuss benefits of the legacy effect and metabolic memory and how they

improve patient outcomes

• Describe evidence for failure to advance or deintensify treatment and the

impact on clinical outcomes

• Identify contributors to therapeutic Inertia in clinical practice

• Describe the pillars of ADAs initiative to identify and promote effective

strategies to reduce therapeutic inertia in clinical practice

4

Disclosures

Kamlesh Khunti, PhD, MD

• I am member of the International Hypoglycemia Study

Group

• Consultant: Amgen, AstraZeneca, BMS, Boehringer

Ingelheim, Janssen, Lilly, MSD, Novartis, Novo Nordisk,

Roche, Sanofi and Servier.

• Research Support: AstraZeneca, Boehringer

Ingelheim, Lilly, MSD, Novartis, Janssen, Novo Nordisk,

Roche and Sanofi

• Speaker’s Bureau: AstraZeneca, Berlin-Chemie AG /

Menarini Group, Boehringer Ingelheim, Janssen, Lilly,

MSD, Napp, Novartis, Novo Nordisk, Roche and Sanofi

5

Therapeutic Advances Over Past 20 Years:

Many Options For Managing T2 Diabetes

GLP-1R agonist

1920 1990 2000 20101970

Insulin SFU

Pramlintide

DPP-4

inhibitor

Bromocriptine

1960 1980

TZD

Metformin

Rapid-actinginsulin

Meglitinide

Basal insulin

2014

αGlucosidase

inhibitor

SGLT-2 Inhibitor

SOC Debuted 1989

6

Advances in health technology, policy, and 10 drug classes and new therapies have NOT translated to improvements in diabetes care quality

Pro

po

rtio

n o

f p

atie

nts

wit

h T

ype

2 D

iab

ete

s

Adapted from: Lipska KJ, Yao X, Herrin J, et al. Trends in drug utilization, glycemic control, and rates of severe hypoglycemia, 2006–2013 [published online September

22, 2016]. Diabetes Care. doi:10.2337/dc16-0985.

DPP-4 and GLP-1 Rx approved

Increased adoption of EHRs, HITECH Act, iPhone

and apps introduced

Affordable Care Act becomes law, proliferation

of “personal tech”

SGLT-2 inhibitor Rx approved

Meaningful UseImplementation, PCMH,

ACO formations

0

10

20

30

40

50

60

70

80

90

100

A1c ≥ …

A1c <…

*Subset of 1.66M patients with an A1c

available

N=424,348*

7

8

Percentage of Patients with Diabetes Achieving A1C <7%

has declined: NHANES Data

56.80%

52.20%

50.90%

0.47

0.48

0.49

0.5

0.51

0.52

0.53

0.54

0.55

0.56

0.57

0.58

2003-2006 2007-2010 2011-2014

Edelman S, Polonsky W. Diabetes Care 201740:1425-1432

Therapeutic Inertia is, in part, responsible for failure to meet goals

THERAPEUTIC INERTIA: The failure to advance or

deintensify the treatment regimen when a patient’s

therapeutic goals are not met.

CLINICAL INERTIA: Includes underuse of therapies and interventions

known to prevent or delay negative outcomes including DSMES, lack of

screening, risk assessment, preventive measures, and referrals.

9

Poll Question #1

ADA Recommendations

to Achieve

Glycemic Targets in

Type 2 Diabetes

Regimen

intensification

Increase dose of

OHA

Add on

Pharmacotherapy

Switch to basal

insulin

Add prandial

insulin

Close Glucose

monitoring

Glycemic targets

A1C

11

Overcoming Therapeutic Inertia Benefit:

Metabolic Memory

Achieving Early Glycemic Control Leads to better Outcomes:

Generates a Positive Legacy Effect (metabolic memory)

Me

dia

n H

bA

1c

(%

)

0

6

7

8

9

UKPDS 1998

ConventionalMetformin

Holman et al 2008

Legacy effect

1997

Difference in HbA1c was lost after first

year but patients in the initial intensive arm

still had lower incidence of any complication:

•24% reduction in microvascular

complications

•15% reduction in MI

•13% reduction in all-cause mortality

2007

MI, myocardial infarction

Diabetes Trials Unit. UKPDS Post Trial Monitoring. UKPDS 80 Slide Set. Available at: http://www.dtu.ox.ac.uk/index.php?maindoc=/ukpds/. Accessed 12

September, 2008;

Adapted from Holman RR, et al. N Engl J Med. 2008; 359: 1577–1589; UKPDS 33. Lancet. 1998; 352: 837–853.13

Adapted from: Khunti K, et al. Diab Care 2013;36:3411–7;’ Del Prato S, et al. Int J Clin Pract 2005;59:1345–1355

HbA

1c

Time

OAD

monotherapy

OAD triple

combination

OAD dual

combinationInsulin

Conventional stepwisetreatment approach

Earlier and more aggressive intervention approach

10

9

8

7

6

8.7%

9.1%

9.7%

8.5%

For all patients

2.9 years 7.2 years

6.7 years

8.4% 8.8%9.0%

For those with HbA1c ≥7%

Early and Appropriate Intervention may

Improve Patients’ Chances of Reaching A1C Goal

14

Legacy Effect in Type 2 Diabetes exists outside

of clinical trial populations

Cohort study of managed care patients with type 2 diabetes and 10 years of survival

followed for 13 years N= 34,737

Diabetes control during the first year after diagnosis was strongly associated with

future risk for diabetes complications and mortality.

15 Laiteerapong N, Ham S, Goo Y, et al. Diabetes Care 2019;42:416-0426

• HR 1.204

• Experiencing micro and macro vascular

complications

Failure to achieve A1C <6.5

In first year

• HR 1.290

• All cause mortalityFailure to achieve A1C<7

In first year

Taking Action to Intensify Therapy Can Reduce Diabetes Related Costs: Retrospective Claims Analysis

21,171 Adults with T2 Diabetes and A1C>7% followed for 18 months

16

• Physician took action

to intensify therapyHigh

Conformance

• Mixed action taken

50% of timeIntermediate

Conformance

• No action taken Low

Conformance

Low vs High Conformance:

• Pharmacy costs were lower in Low

Conformance*

• Diabetes Outpatient related costs 60%

higher in Low Conformance at 18 months*

Intermediate vs High Conformance

• Diabetes related Outpatient Costs were

higher at 12 and 18 months*

*P <.0001

Mehta R, et al. Journal of Clinical & Translational Endocrinology. 19(2020) 100215

Therapeutic Inertia in Clinical Practice

• Khunti K, et al. Diabetes Care 2013;36:3411–7

Substantial inertia exists at each sequential intensification step

6.9-7.2 years11.6-2.9 years1 6-7.1 years1 3.7 years2

Patient

on 1

OAD

Adding

2nd

OAD*

Adding

3rd

OAD*

Adding

insulin*

Adding

GLP-1 RA,

Premixed

and bolus

insulin†

Documented delays in therapy intensification for

people not meeting glycemic targets

*From time when A1c was ≥7.0%, ≥7.5%, or ≥8.0%; †From time when A1c was ≥7.5%.

GLP-1 RA: glucagon-like peptide-1 receptor agonist; OAD: oral antidiabeticdrug.

Slide courtesy of Steve Edelman, MD.1. Khunti K, et al. Diabetes Care. 2013;36:3411-3417. 2. Khunti K, et al. Diabetes Obese Metab.2016;18:401-409.

18

Treatment Intensification In Patients With Type 2 Diabetes Who

Failed Metformin MonotherapyTime To Treatment Intensification For All Patients (A), By Index HbA1c Level (B), By Metformin Daily Dose (C)

0.00

0.25

0.50

0.75

1.00

Pro

po

rtio

n o

f P

ati

en

ts o

n

Metf

orm

in M

on

oth

era

py

A.

Median = 14.0 mo

0 1 2 3 4 5

Years

Index HbA1c 8-<9%Median = 8.7 mo

0.00

0.25

0.50

0.75

1.00

B.

Index HbA1c 7-<8%Median = 19.0 mo

0 1 2 3 4 5

Years

Index HbA1c ≥9%Median = 4.5 mo

0.00

0.25

0.50

0.75

1.00

C.

Always <1500 mgMedian = 20.0 mo

0 1 2 3 4 5

Years

Ever ≥1500 mgMedian = 8.9 mo

Fu et al. Diabetes, Obesity and Metabolism; 2011;13: 765–769

19

Mean pre-insulin HbA1c by

country is 8.3-9.8%

8.9

8.3

8.5

9.4

9.2

8.4

9.1

8.9

9.8 9.8

7.5

8.0

8.5

9.0

9.5

10.0

Canada China Germany Israel Italy Poland Portugal Spain Turkey UK

Pati

en

ts,

% Patients remain poorly controlled on

OAD treatment for prolonged periods

of time

At insulin initiation in SOLVE, mean

pre-insulin HbA1c range was between

8.3% (China) and 9.8% (Turkey/UK)

SOLVE: 24-week observational study involving 10 countries that assessed safety and effectiveness

of initiating QD insulin detemir in patients with T2DM treated with ≥1 OADs

Insulin Initiation is Generally Delayed

Khunti K, et al. Diab Obes Metabolism. 2012;14:1129‒36

20

a ≥ 6 months after starting basal insulin

Product-limit survival estimate,

with number of patients at risk

Median time from initiation of

basal insulin to intensification

was

3.7 years [95% CI: 3.4;4.0]

1.0

0.8

0.6

0.4

0.2

0.0

Su

rviv

al

pro

bab

ilit

y

Time from HbA1c ≥ 7.5% (58 mmol/mol) to intensification with bolus, premix, or GLP-1 (years)

0

6,072 At risk (n)1,652 461 137 27 04632568723,066

8642 10

Survivalprobability:

0.5

3.7 years[95 CI: 3.4; 4.0]

Patients with HbA1c ≥ 7.5%a

Intensification to Add Basal Insulin Lags Time from initiation of basal insulin therapy to intensification with bolus or premix insulin or GLP-1

(n= 11,696)

Khunti K, et al. Diabetes Obes Metab. 2016. DOI:10.1111/dom.12626.

21

0.00

0.10

0.20

0.30

0.40

0.50

China Poland UK Germany Israel Spain Turkey Canada Portugal Italy

In

su

lin

do

se,

U/

kg

Insulin at start

Final visit dose

n = 17,374

SOLVE:1,2 24 week observational study of once-daily (QD) insulin detemir in patients with T2DM receiving OADs

Treat-to-target trials often report higher insulin doses

compared to those recorded in observational trials, such as

SOLVE

In one treat-to-target trial, insulin-naïve patients were titrated to receive insulin

detemir QD or glargine QD3

After 52 weeks, the mean daily insulin detemir dose (n=227)

was 0.78 U/kg

Titration Inertia: Patients Remain at Low Basal Insulin

Doses

1. Khunti K, et al. Diabetes Obes Metab 2012;14:654–661

2. Khunti K, et al. Diabetes Obes Metab 2012;14:1129–36

3. Rosenstock J, et al. Diabetologia 2008;51:408–16

22

Legacy Effect: Achieving Control Early in Diagnosis and

Treatment Creates Metabolic Memory

• Early glycemic control leads to lower A1C

• Early intensification of treatment is associated with a shorter time to

achieving glycemic control

• Early glycemic control leads to better maintenance of control for a

longer period of time

• Early glycemic control leads to better long term health outcomes and

lower risk of microvascular and macrovascular complications.1

1. M Abdul-Ghani, C Puckett, et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in

subjects with new-onset diabetes. Results from the efficacy and durability of initial combination therapy for type 2 diabetes (EDICT): a randomized trial. Diabetes

Obes Metab 2015; 17: 268–275.

2. D Mauricio, L Meneghini, et al. Change in insulin dose and HbA1c by geographical region—results from the diabetes unmet need with basal insulin evaluation

(DUNE) Study. Diabetes 2018; 67(Suppl. 1). DOI: 10.2337/db18-1037-P.

3. U Desai, NY Kirson et al. Time to treatment intensification after monotherapy failure and its association with subsequent glycemic control among 93,515 patients

with type 2 diabetes. Diabetes Care 2018; 41: 2096–2104.23

Disclosures

Stephen Brunton, MD

Advisory Panel – Abbott, AstraZeneca Diabetes NovoNordisk

Bayer U.S.., Xeris Pharmaceuticals, Sanofi Inc.

Speaker's Bureau – AstraZeneca Lilly Diabetes. Novo Nordisk,

Xeris.

24

Contributing Factors to

Therapeutic Inertia

The Causes of Therapeutic inertia are Multifactorial:

• People with diabetes

• Clinicians and healthcare providers

• Healthcare systems

• Payors

• Industry

26

What stakeholders say is needed to REDUCE therapeutic inertia…

Most Frequently Cited Promotors of Therapeutic Inertia

Adapted from :G Reach, V Pechtner, et al.; Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus; Diabetes &

Metabolism Vol 43, Issue 6, Dec. 2017, 501-511

Addressing Therapeutic Inertia in 2020 and Beyond: A 3-Year Initiative of the American Diabetes Association, Clinical Diabetes July 31, 2020;

Physician-Related

• Time constraints and

overwhelming

requirements

• Fear of aggressive therapy

causing side effects such as

hypoglycemia.

• Failure to initiate, evaluate

or intensify treatment

using goals and targets.

• Underestimation of

patient's needs and abilities

to manage their own

diabetes

Patient-Related

• Cost of and access to

medication/poor insurance

coverage

• Limited understanding of

the chronic nature of

diabetes & treatment as

progressive

• Poor participation in

diabetes education (6%)

• Poor communication/trust

between physician and

patient

System-Related

• Failure of system to

identify patients at risk

of TI

• Lack of transparency or

accuracy in formulary at

POC

• Failure to provide access

to Diabetes Ed. (DSMES)

• No team approach to

care

28

Overcoming Therapeutic Inertia Initiative

AIM: Promote the adoption of evidence-

based practices, strategies, programs and

tools that address key determinants of

therapeutic inertia in diabetes care,

leading to improved, timely treatment

modification and improved glycemic

control in adult patients with type 2

diabetes.

Overcoming Therapeutic Inertia Initiative

31

Through the OTI initiative, ADA is ushering in

a paradigm shift in the care of type 2

diabetes, advancing the latest thought-

leadership, resources, and tools in

overcoming therapeutic inertia for primary

care.

Make Information Accessible

Improve Processes and

Workflow

Develop Consensus and Evaluate Impact

• Develop professional and patient education resources

• Carry out multidimensional awareness campaign

• Supervise research• Curate effective approaches

database• Plan potential pragmatic trials• Evaluate success

• Develop consensus• Encourage innovative EHR tools• Improve payer practices• Support ADA policy initiatives

RESEARCH(Identifying

Best Practices)

EDUCATION &

AWARENESS(Promoting

Clinician Success)

COLLABORATIVE

BARRIER BUSTING(Forming Alliances)

Initiative Priorities

OTI Best Practices Framework Overview

Pillar 1: Empower Patients (build engagement and trust)

1. Schedule Diabetes-Only Visits

2. Set & Track Shared Targets & Timeframes

3. Integrate Screening for Social, Emotional,

Cultural and Health Literacy Issues and Provide

Support

4. Use Thoughtful Prescribing – Consider cost,

insurance, preferences, etc.

5. Refer to Diabetes Self Management Education &

Support - DSMES (refer, follow-up, refer again)

Be a

Barrier

Buster

CORE QUESTION…Does every patient know you are their champion?

Pillar 2: Optimize Care & Treatment (person-centered and evidence-based)

1. Conduct Practice-Based Screening for Likely

Therapeutic Inertia

2. Use Personalized Diabetes Care Plans

3. Use a Team-Based Approach to increase frequency and

quality of engagement (leverage everybody at the top

of the license)

4. Use Glucose Data + A1C to Drive Rapid Cycle

Treatment Intensification (go beyond A1C)

5. Stratify Follow Up Based on A1C & Recent Therapy

Change

Act Now

CORE QUESTON…Have you done everything in your control

to optimize therapy and support adherence at every visit?

And between visits?

Pillar 3: Leverage Tools and Tech (for enhanced decision support)

1. Adopt a Diabetes Treatment Algorithm and have it

available at POC (simple and unambiguous) –

consider ADA’s SOC App.

2. Create & Use a Patient Registry

3. Integrate Decision Support into Workflow

4. Adopt Technology to Increase Number and Quality of

Touchpoints (telehealth, texting, patient portals)

5. Disseminate Unblinded Quality Metrics – Learn from

other’s successes

Improve

Decision

Making

CORE QUESTION…Have you made it easy for everyone in

your practice to make high quality treatment decisions

quickly and consistently?

Understand

therapeutic

inertia (TI)

Notice TI in

People with

Diabetes

Inform PWD

about Long-Term

Diabetes

Management

Create

Personalized

Treatment and

Care Plans

Engage a

Multidisciplinary

Team &

Community

Support

Detect Barriers

to Self-

Management

and Refer

UNITED in

Overcoming

Therapeutic Inertia

Timely Therapy Optimization

Do something at every visit over target

Improved CarePlan Adherence

Continuously assess and address

barriers

All Strategies Aim to Drive Either…

Inertia

Busting

At the end of each visit, ask the question…

Do I feel reasonably certain that I have done everything

within my sphere of control to help this patient with

optimizing therapy & removing barriers to achieve the

agreed upon A1C target within the next 3 months?

38

Adopt a “Barrier Busting” Mentality

7 Easy Strategies to Overcome Inertia Tomorrow

1. Identify and engage patients with “Likely TI” in your clinical practice. For example,

obtain list of all patients with no office visit in the last 4 months and an A1C > 9%.

2. Start scheduling “diabetes only” visits where you and your patients can focus solely on

diabetes. Ask your office staff to remind patients to bring their glucose logs, list of

medications, and monitoring devices.

3. Arrange more frequent office visits based on A1C and recent treatment change.

Leverage telehealth to make this happen. For example, every 6 to 8 weeks for those at

9% or higher, every 2 to 3 months for those between 7 and 8.9%, and every 3 to 6 months

for those <7% or at their personal target.

4. Check patients for barriers such as diabetes distress, depression, low health literacy,

and social determinants of health.

5. Refer all patients for DSMES – it works!

6. Develop a care and treatment plan with each patient that includes a personalized A1C

target and takes his or her needs, concerns, and wishes into account. Review and update

it regularly.

7. Aim to adjust therapy any time a patient’s A1C or other targets are not at goal.

Consider making changes between A1C tests based on monitoring results. Start utilizing

A1C + glucose data to drive rapid cycle treatment optimization – Go Beyond A1C

39

Poll Question #2

Summary

• Therapeutic Inertia is the failure to advance or de-intensify the

treatment regimen when a patient’s therapeutic goals are not met.

• Early glycemic control provides a legacy effect positively impacting

patient outcomes

• Addressing contributors to therapeutic inertia at the patient, practice,

and system can help overcome therapeutic inertia

• There are simple things you can do right now to more rapidly

optimize treatment and to remove barriers to care plan adherence –

both essential to overcoming therapeutic inertia

41

Tom was devasted by his diagnosis of diabetes 3 months

ago. His dad had type 2 diabetes and died within a year of

going on insulin. He wants to use weight loss to get his

A1C of 9.5 % down but admits it is hard.

At his appointment this week Tom’s A1C is 9.2%. You

discuss adding metformin and an SGLT2 and refer him to

the local diabetes educator and dietitian. He does not

want to take 2 medications due to cost and doesn’t think

he is that sick.

Tom lives by himself an hour away from your office and

from the diabetes educator at the hospital. You ask him to

schedule a follow up in 30 days.42

CASE STUDY: What might be contributing to therapeutic

inertia in this scenario? What could you do?

Questions?

43

Your Action Assignment - Should you choose to accept it!

1. Download and share: (also available on website below)

• OTI Fact Sheet: Getting to Goal: Overcoming

Therapeutic Inertia in Diabetes Care

• OTI Best Practices Framework

• OTI White Paper - Addressing Therapeutic Inertia in

2020 and Beyond: A 3-Year Initiative of the American

Diabetes Association

2. Take the post-webinar survey

Learn more at…TherapeuticInertia.Diabetes.org

44

Upcoming Therapeutic Inertia Webinars

9/23/2020 Busting Inertia: Identifying and Engaging High-Risk

Patients

11/4/2020 Leveraging Personalized Diabetes Care Plans to

Overcome Therapeutic Inertia

12/16/2020 Break Through Inertia: Strategies to Make Your Practice

the Intervention

1/27/2021 Engaging Your Community as an Inertia Buster

3/10/2021 Optimize the Patient Journey: A Case-Based Approach

45

Other Therapeutic Inertia Components Coming Soon…

1. Practice Pearls videos series on overcoming

therapeutic inertia

2. Online OTI Self-Assessment Tool for Clinicians

3. Free Online “Diabetes Consumer Guide Tool” –

compare devices, drugs and more!

4. Patient & Provider Conversation Guide and Toolkit

5. Customizable Patient Care and Treatment Plan

46

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