Diabetes 3. Compare and contrast the ADA (American Diabetes [PDF]

SLIDE 1

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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Diabetes

Is your formulary in line with guidelines?

JENNIFER D. GOLDMAN, RPH, PHARMD, CDE, BC-ADM, FCCP PROFESSOR OF PHARMACY PRACTICE, MCPHS UNIVERSITY, BOSTON, MA CLINICAL PHARMACIST, WELL LIFE MEDICAL, PEABODY, MA

Learning Objectives

1. Review the epidemiology and global/US impact on morbidity,

mortality and cost

2. Discuss the metabolic progression of diabetes and why to choose

specific drug therapies for this pathophysiology

3. Compare and contrast the ADA (American Diabetes Association) and

the AACE/ACE (American Association of Clinical Endocrinologists and American College of Endocrinology) guidelines for the therapeutic management of hyperglycemia in patients with diabetes

4. Identify and discuss the rationale for combination therapy for the

treatment of T2DM

5. Utilizing a patient case, apply the guidelines to choose appropriate

drug therapy for treatment

How much experience in the room?

a. < 10 years
b. 11-19 years
c. 20-29 years
d. 30+ years

Do you think your formulary matches the current guidelines?

a.Yes b.No

How many Americans develop diabetes every day (24 hours)?

a. 589

b.1200

c. 2450

d.3250

e. 4109

What was the total cost of diabetes in the US (2017) per day (24 hours)?

a. $27 million
b. $145 million
c. $342 million
d. $578 million
e. $896 million

SLIDE 2

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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What percentage of patients in the US do NOT achieve recommended A1C goals despite initiation of diabetes drug therapy?

a. 8%

b.17%

c. 37%

d.49%

e. 72%

Many patients with diabetes remain above the ADA-recommended A1C target

a 2007-2010 US population. Data derived from the National Health and Nutrition Examination Survey (NHANES)

and from the Behavioral Risk Factor Surveillance System (BRFSS). 1. Ali MK et al. N Engl J Med. 2013;368(17):1613-1624. 8

49%

A1C >7% Total US population with diabetes mellitusa

21%

A1C >8% A1C levels in US patients with diagnosed diabetes

Increasing prevalence of diabetes

In 2015, 30.3 million people in the United States had diabetes By 2030, diabetes is predicted to affect 1 in 3 adults – 55 million adults

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Estimated total cost of Diagnosed diabetes in 2012 was $245 billion

1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Estimates of diabetes and its burden in the United States. Available online:

https://stacks.cdc.gov/view/cdc/46743. Accessed February 23, 2018. 2. Rowley WR, Bezold C, Arikan Y, et al. Diabetes 2030: Insights from yesterday, today, and future trends. Popul Health Manag. 2017;20(1):6-12. 3. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36:1033-1046.

1 2 3 CV death All-cause mortality Hazard ratio (95% CI) (diabetes vs no diabetes)

Type 2 diabetes is increasingly prevalent

IDF DIABETES ATLAS 6TH EDITION 2014 HTTP://WWW.IDF.ORG/DIABETESATLAS; 2. CENTERS FOR DISEASE CONTROL AND PREVENTION 2011; 3. SESHASAI ET AL. N ENGL J MED 2011;364:829-41 10

At least 68% of people >65 years with

diabetes die of heart disease2

This will rise to 592 million by 20351 Mortality risk associated with diabetes (n=820,900)3

Globally, 387 million people are

living with diabetes

Complications of Diabetes – morbidity/morality

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Cardiovascular Disease Stroke 2- to 4-fold increase in cardiovascular mortality and stroke Diabetic Retinopathy Leading cause of blindness in adults Diabetic Nephropathy Leading cause of end-stage renal disease Diabetic Neuropathy Leading cause of non-traumatic lower extremity amputations 8/10 individuals with diabetes die from CVD

a. UKPDSG. Diabetes Res. 1990;13:1-11; b. Fong DS, et al. Diab Care. 2003;26(Suppl 1):S99-S102; c. HDS. J Hypertens. 1993;11:309-317; d. Molitch ME, et al. Diab Care. 2003;26(Suppl

1):S94-S98; e. Kannel WB, et al. Am Heart J. 1990;120:672-676; f. Haffner SM, et al. N Engl J Med. 1998;339:229-234; g. Diabetes organization website; h. Mayfield JA, et al. Diab Care. 2003;26(Suppl 1):S78-S79.

Lowering your A1C by 1% lowers your risk of microvascular complications (eyes, kidneys, nerves) by approximately _____ %

a. 10%

b.20%

c. 40%

d.60%

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SLIDE 3

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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Percent risk reduction of diabetes-related complications in patients with T2DM for each 1% decrease in A1C

37%

P<0.0001

43%

P<0.0001

21%

P<0.0001

14%

P<0.0001

14%

P<0.0001 MYOCARDIAL INFARCTION DIABETES- RELATED DEATH MICROVASCULAR COMPLICATIONS AMPUTATION OR PVD DEATH ALL-CAUSE MORTALITY

UKPDS 10-year follow-up showed a “legacy” effect: continued risk reduction for microvascular complications and emergent risk reduction for myocardial infarction and death from any cause2 Study design: Prospective observational study of 4585 UKPDS patients with T2DM from 23 hospital-based clinics in the United Kingdom. Total of 3642 patients were included in relative-risk analyses. Data adjusted for age, blood pressure, gender, ethnic background, smoking, albuminuria, HDL, LDL, and triglycerides.

Stratton IM et al. BMJ. 2000;321(7258):405-412. Holman RR et al. N Engl J Med. 2008;359(15):1577-1589.

Patient Case- where do the guidelines fit?

48 year old male, new to practice (6/16), established with PCP, and referred to Pharmacy for medication management. Reports poor diet, but no complaints of fatigue, polyuria, polydipsia, no GI complaints. PMH: T2DM (2005), hypertension, hyperlipidemia, morbid obesity, vitamin D deficiency, previous ETOH abuse (2014) SH: married, 3 children, one PharmD candidate, owner of liquor store and restaurant, past smoker 1 ½ packs per day, NKDA Medications: glipizide 15mg bid and metformin IR 1000mg bid Other: atorvastatin 10mg qd, hctz 12.5mg qd , valsartan 320mg qd, aspirin 81mg qd Pertinent labs/vitals: A1C 9.5%, 404lbs, BMI 63.3, BP 117/79 P79, CMP WNL, eGFR > 60, negative albuminuria, vitamin D 13, vitamin B12 254, FLP TC 124, TG 150, HDL 39, LDL 55, TSH wnl

According to the ADA guidelines which of the following agents should be added after metformin for most patients?

a. Basal insulin (ie glargine/Lantus™)
b. Sulfonylurea (ie glipizide/Glucatrol™)
c. GLP-1RA (ie liraglutide/Victoza™)
d. DPP-4 inhibitor (ie sitagliptin/Januvia™)
e. Any of the above

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According to the AACE guidelines which of the following agents should be added after metformin for most patients?

a. Basal insulin (ie glargine/Lantus™)
b. Sulfonylurea (ie glipizide/Glucatrol™)
c. GLP-1RA (ie liraglutide/Victoza™)
d. DPP-4 inhibitor (ie sitagliptin/Januvia™)
e. Any of the above

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Glycemic Targets Recommended in Consensus-Based Guidelines: Nonpregnant Adults

Parameter

ADA AACE

A1C level <7.0% ≤6.5% Preprandial plasma glucose (fasting) 70–130 mg/dL <110 mg/dL Peak postprandial plasma glucose <180 mg/dL (2 h after start

f meal)

<140 mg/dL (2 h after start

f meal)

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*Appropriate for most, but should be tailored to patient circumstance.

Glycemic Targets: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S55-S64

Approach to the Management of Hyperglycemia

low high newly diagnosed long-standing long short absent severe Few/mild absent severe Few/mild

highly motivated, adherent, excellent self-care capabilities

readily available limited

less motivated, nonadherent, poor self-care capabilities

A1C 7% more stringent less stringent

Patient/Disease Features

Risk of hypoglycemia/drug adverse effects Disease Duration Life expectancy Important comorbidities Established vascular complications Patient attitude & expected treatment efforts Resources & support system

Glycemic Targets: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S55-S64

SLIDE 4

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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30% 70% 70% 30% 20 40 60 80 100 <7.3 7.3-8.4 8.5-9.2 9.3-10.2 >10.2

Both PPG and FPG contribute to A1C in patients with diabetes

A1C ranges (%) A1C >8.4%:

FPG contributes 50%
r more to

hyperglycemia A1C ≤8.4%:

PPG contributes 50%
r more to

hyperglycemia Contribution (%)

Study design: A consecutive 1-day study of 290 insulin-naive patients with T2DM. Overnight-fasted patients were divided into 5 groups of A1C ranges, based on high-pressure liquid chromatography assays. Blood samples were drawn at 3-hour intervals from 8:00 am to 5:00 pm. Patients received standard meals. On study days, patients took usual doses of metformin, glyburide, or both.

Monnier L et al. Diabetes Care. 2003;26(3):881-885. FPG PPG

T2DM Is a Progressive Disease Involving Multiple Metabolic Abnormalities

Insulin resistance Insulin level Glucagon level Incretin effect Beta-cell function Pre-diabetes (IFG/IGT) Diabetes diagnosis

250 200 150 100 50

Relative Amount

–15 – 10 – 5 5 10 15 20 25 30

Diagnosis of Diabetes (years)

Onset Diabetes Kendall DM et al. Am J Med. 2009;122(6A):S37-S50 Gromada J et al. Endocr Rev. 2007;28(1):84-116.

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Class A1C lowering (%)

monotherapy

Insulin (add on) 1.5-3.5 (or >) Sulfonylureas 1-2 Biguanides 1-2 Alpha-glucosidase inhibitors 0.5-0.8 Glitazones 0.5-1.4 Glinides 0.5-1.5 GLP-1 RAs 0.5-1.6 Amylin analogues 0.5-1 DPP-4 inhibitors 0.5-0.8 Bile acid sequestrants 0.5 Dopamine 2 agonists 0.5 SGLT2 inhibitors 0.5-1.2

Type 2 diabetes: A multifactorial disease OMINOUS OCTET

HYPERGLYCEMIA

LIVER

Increased endogenous glucose production

MUSCLE

Reduced glucose uptake

PANCREAS (b-cells) Decreased

insulin secretion

FAT

Increased free fatty acids (lipolysis)

BRAIN

Neurotransmitter dysfunction

KIDNEY

Increased glucose reabsorption

PANCREAS (α-cells)

Increased glucagon secretion

INTESTINE

Decreased incretin effect

DeFronzo RA. Diabetes. 2009;58(4):773-795. Shwartz et al. Diabetes Care. 2016;39(2):179-86. Egregious Eleven 1. Incretin effect 2. Immune dysregulation & inflammation 3. Colon/biome

Consider combining therapies that target different pathophysiologic abnormalities

AGi, α-glucosidase inhibitor; DPP4i, dipeptidyl peptidase-4 inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonist; MET, metformin; SGLT2i, sodium-glucose co-transporter-2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione.

HYPERGLYCEMIA

Insulin, TZD, MET GLP-1-RA, DPP-4-I

LIVER

Insulin, TZD

MUSCLE

GLP-1-RA, DPP-4-i, SU

PANCREATIC β-CELLS

Insulin, TZD

FAT

GLP-1-RA

BRAIN

SGLT2-I

KIDNEY

GLP-1-RA, DPP-4-I

PANCREATIC α-CELLS

AGi, GLP-1- RA

INTESTINE Ferrannini E et al. Eur Heart J. 2015;36(34):2288-2296. ADA. Diabetes Care. 2017;40(suppl 1):S1-S135. 24

“Star Struck”

Ralph Defronzo, January 2016

SLIDE 5

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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25 American Diabetes Association Standards of Medical Care in Diabetes. Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74

According to the ADA guidelines which of the following agents should be added after metformin for most patients?

a. Basal insulin (ie glargine/Lantus™)
b. Sulfonylurea (ie glipizide/Glucatrol™)
c. GLP-1RA (ie liraglutide/Victoza™)
d. DPP-4 inhibitor (ie sitagliptin/Januvia™)
e. Any of the above

26

Antihyperglycemic Therapy in Adults with T2DM

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85 Next 2 slides- blown up Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85 Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

In patients with T2DM and established ASCVD, antihyperglycemic therapy

should begin with lifestyle management and metformin and subsequently incorporate an agent proven to reduce major adverse CV events and CV mortality (currently empagliflozin and liraglutide), after considering drug-specific and patient factors (Table 8.1).

In patients with T2DM and established ASCVD, after lifestyle management and

metformin, the antihyperglycemic agent canagliflozin may be considered to reduce major adverse CV events, based on drug-specific and patient factors (Table 8.1).

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

Pharmacologic Therapy For T2DM: Recommendations

SLIDE 6

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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32 Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes -

2018. Diabetes Care 2018; 41 (Suppl.

1): S73-S85

According to the AACE guidelines which of the following agents should be added after metformin for most patients?

a. Basal insulin (ie glargine/Lantus™)
b. Sulfonylurea (ie glipizide/Glucatrol™)
c. GLP-1RA (ie liraglutide/Victoza™)
d. DPP-4 inhibitor (ie sitagliptin/Januvia™)
e. Any of the above

34

SLIDE 7

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

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Approximately how many emergency room visits yearly for hypoglycemia in patients over 18yo with diabetes?

a. 10,000

b.70,000

c. 150,000

d.280,000

37

10

Many patients not assessed per guidelines

A study evaluated patients for assessment per

ADA guidelines in the following manner:

42,837 patients were evaluated for A1C

testing frequency

Follow up A1C test within 3 months if

A1C value ≥ 7%

Follow up A1C test within 6 months if

A1C value < 7%

95,330 patients were evaluated for antidiabetic

treatment modification

Modification within 45 days of A1C ≥ 7%

Study Results

14% 18% 3%

Met A1C testing frequency guideline Met guideline for both A1C testing frequency and treatment modification Met treatment modification guideline American Diabetes Association. Standards of medical care in diabetes –2018. Diabetes Care. 2018;41(suppl 1):S1-S159. LianJ, Liang Y. Diabetes management in the real world and the impact of adherence to guideline recommendations. Curr Med Res Opin. 2014;30(11):2233-2240.

There Is a Delay in Intensifying Treatment in Those With Type 2 Diabetes and Suboptimal Glycemic Control

7 6 5 4 3 2 1 6.9 years 3.7 years 1.6 years 3 months Patients with A1C ≥8% taking 2 OADs Patients with A1C ≥7.5% on basal insulin Patients with A1C ≥ 8 taking 1 OAD ADA and AACE recommendation

American diabetes association. Standards of medical care in diabetes –2018. Diabetes care. 2018;41(suppl 1):S1-S159. Garber AJ, abrahamson MJ, barzilay JI, et al. Consensus statement by the american association of clinical endocrinologists and american college

f endocrinology on the comprehensive type 2 diabetes management algorithm –2018 executive summary. Endocr pract. 2018;24(1):91-120. Khunti K, wolden ML, thorsted BL, andersen M, davies MJ. Clinical inertia in people with type 2 diabetes. Diabetes care.

2013;36(11):3411-3417. Khunti K, nikolajsen A thorsted BL, andersen M, davies MJ, paul SK. Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. Diabetes obes metab. 2016;18(4):401-409.

Drug Selection Degree

f A1C-

lowering required Which glucose level is not at target? Side-effect profile Coexisting medical conditions Duration of disease Patient preferences

Selecting Pharmacotherapy: Individualization Is the Key

40

Do you think your formulary matches the current guidelines?

a.Yes b.No

Patient Case

48 year old male, new to practice (6/16), established with PCP, and referred to Pharmacy for medication management. Reports poor diet, but no complaints of fatigue, polyuria, polydipsia, no GI complaints. PMH: T2DM (2005), hypertension, hyperlipidemia, morbid obesity, vitamin D deficiency, previous ETOH abuse (2014) SH: married, 3 children, one PharmD candidate, owner of liquor store and restaurant, past smoker 1 ½ packs per day, NKDA Medications: glipizide 15mg bid and metformin IR 1000mg bid Other: atorvastatin 10mg qd, hctz 12.5mg qd , valsartan 320mg qd, aspirin 81mg qd Pertinent labs/vitals: A1C 9.5%, 404lbs, BMI 63.3, BP 117/79 P79, CMP WNL, eGFR > 60, negative albuminuria, vitamin D 13, vitamin B12 254, FLP TC 124, TG 150, HDL 39, LDL 55, TSH wnl

SLIDE 8

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

8 Course of treatment - Pharmacy visit 1 6/16

At that first visit the following occurred (besides education)

Start tapering off glipizide; decrease from 30mg daily to 15mg daily

with plan to stop in 1 month (WHY???)

Initiate liraglutide 0.6mg daily x 7 days, then increase to 1.2mg daily

x 7 days, then 1.8mg daily thereafter

PATIENT COUNSELING
Reassess and determine if basal insulin or SGLT-2 inhibitor may be

needed next visit

Course of treatment: Pharmacy visit 2 8/16, PCP-10/16

Monitoring PP and FBS at home; brought to visit
Weight is now 395lbs (13lb weight loss 2 months), BP 121/79
Discontinue the 15mg of glipizide
Continue liraglutide 1.8mg daily
Initiate empagliflozin 10mg x 2 weeks then increase to 25mg; discontinue HCTZ 12.5mg
PATIENT COUNSELING
Reassess; if symptomatic consider basal insulin
F/U with PCP 10/16 A1C 6.6%: continue metformin IR 1000mg bid, liraglutide 1.8mg qd,

empagliflozin 25mg qd, weight 372 (36lbs), BP 120/67

Course of treatment: Pharmacy visit 3 1/17, PCP 4/17, 7/17

A1C 7.2%, weight 354lbs (54lb weight loss), BP 124/60
Continue liraglutide 1.8mg daily; change to empagliflozin/metformin

ER 12.5/1000mg 2 tablets once a day (why?)

4/17 PCP F/U DM: A1C 6.3%, 340lbs (68lb weight loss), BP 124/70
7/17 PCP Physical: A1C 6.0%, 327lbs (81lbs weight loss), BP 124/64

Course of treatment: Pharmacy visit 4 8/17 visit 5 11/17

Visit 4

A1C 6% (last month), 315lbs (93lb weight loss), BP 118/78
Decrease liraglutide 1.2mg daily and continue empagliflozin/metformin ER

12.5mg/1000mg 2 tablets daily Visit 5

A1C 6% 310lbs (98lbs weight loss), BP 108/66
Monitor BP and symptoms of hypotension; consider decreasing valsartan

Course of treatment: Pharmacy visit 6, combined with PCP 3/18

A1C 5.9%, 297lbs (111lb weight loss), BP 124/74, rare dizziness

when bends over at restaurant

Decrease valsartan from 320mg daily to 160mg daily; reassess in 1

month

Continue current therapy for diabetes, monitor for hypoglycemia- if

needed

Chronic disease state management Collaborative practice

Must include the patient on the team
Prioritize timely and appropriate intensification of therapy
Include all members of a care team, including nurses, dieticians, pharmacists
Team based diabetes care supported by all major organizations
Combination therapy is key*
Choose the best therapy for the patient following established guidelines and what is BEST for

that individual patient

Improving Care and Promoting Health in Population: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S7-S12

SLIDE 9

August 2018 Jennifer D. Goldman, PharmD, CDE, BC-ADM, FCCP Professor of Pharmacy, MCPHS Unversity

9 Contact information

Email: jennifer.goldman@mcphs.edu
Linkedin: www.linkedin.com/in/jenniferdgoldman
Twitter: @jennifergoldman
Practice website: https://www.welllifemedical.org/
MCPHS University: www.mcphs.edu
ADA 2018 standards of care available at: https://professional.diabetes.org/content-page/standards-

medical-care-diabetes

AACE 2018 comprehensive algorithm available at: https://www.aace.com/publications/algorithm