Diabetes Care Update 2016elearning.pharmacist.com/.../Diabetes_Update_2016_HANDOUT_021… · Diabetes Care Update 2016, is approved for 1 hour of continuing pharmacy education credit

Diabetes Care Update 2016

Thursday, February 25, 20162:00 PM – 3:00 PM ET

Speaker

Jennifer D. Smith, PharmD, CPP, BC-ADM, CDE

Associate Professor

Campbell University College of Pharmacy & Health Sciences

Clinical Pharmacist Practitioner

Wilson Community Health Center

Wilson, North Carolina

Disclosures

Jennifer D. Smith, PharmD, CPP, BC-ADM, CDE, and APhA’s editorial staff declare no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.

For complete staff disclosures, please go to APhA’s Accreditation Information webpage at www.pharmacist.com/apha-disclosures.

© 2016 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A. 1

http://www.pharmacist.com/apha-disclosures

Development and Support

This activity was developed by the American Pharmacists Association and supported by an independent educational grant from The Kroger Company.

Attendance Code (live webinar only)

DM16To obtain CPE credit for this live webinar, you are required to actively participate in the entire activity. The attendance code is needed to access the assessment questions to complete the CPE form for this activity. Detailed information on how to claim credit will be provided at the end of the webinar.

Your CPE must be filed by March 25, 2016 at 5:00 PM ET in order to receive credit.

Accreditation Information

The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity, Diabetes Care Update 2016, is approved for 1 hour of continuing pharmacy education

credit (0.1 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 0202-0000-16-088-L04-P.

To obtain continuing pharmacy education credit for this activity, participants will be required to actively participate in the entire webinar and complete an assessment and evaluation by March 25, 2016.

Initial Release Date: February 25, 2016Target Audience: Kroger pharmacists providing the best diabetes careActivity Type: Application-basedLearning Level: 2Fee: There is no fee to participate in this activity


Learning Objectives

Summarize important recent changes to the American Diabetes Association (ADA) Standards of Medical Care in Diabetes and other authoritative guidelines.

Describe evidence regarding the risks and benefits of new and emerging medications and products for the management of patients with diabetes.

Identify noteworthy findings from recent large clinical trials that have potential to influence diabetes care.

Explain how to apply emerging information to the care of patients with diabetes.

Question 1SGLT2 inhibitors have been associated with:

A. Joint pain

B. Heart failure

C. Euglycemic diabetic ketoacidosis (DKA)

D. Worsening albuminuria

Question 2In which disease state should DPP-4 inhibitor treatment be used cautiously?

A. Mild renal impairment

B. Rheumatoid arthritis

C. Recurrent UTI

D. Osteoporosis


Question 3Which was a finding of the treatment arm in the EMPA-REG Outcome Study?

A. Increased incidence of DKA

B. Increased incidence of bone fractures

C. Decreased incidence of genital infections

D. Decreased incidence of cardiovascular (CV) death

ADA STANDARDS OF MEDICAL CARE IN DIABETES—2016

Strategies for Improving Care

Recognizes the impact of food insecurity, homelessness, cognitive impairment, and HIV on glycemic control

– Glipizide as preferred sulfonylurea in food insecurity

– Second-generation antipsychotic: monitor changes in weight, blood glucose, and cholesterol and reassess treatment regimen

– Patients with HIV should be screened for diabetes and pre-diabetes with a fasting glucose level before starting antiretroviral therapy and 3 months after starting or changing it

• Normal: check annually

• Pre-diabetes: measure every 3-6 months to monitor for progression

Diabetes Care. 2016;39:S6–S12.


Classification and Diagnosis of Diabetes

Test all adults at age ≥45 years for diabetes, regardless of weight

Test at any age if overweight/obese and 1+ risk factors for diabetes


Obesity Management for Treatment of T2D

• >16 sessions in 6 months

• Focus on diet, physical activity, and behavioral therapy

• Goal: 500-750 kcal/day energy deficit

• Weight loss medications considered if BMI >27 kg/m2

• Bariatric surgery considered if BMI >35 kg/m2

High-intensity plan to achieve 5% weight loss

• Monthly contact

• Monitor body weight (weekly or more frequently)

• Continue reduced caloric intake

• High levels of physical activity (200–300 minutes/week)

Weight maintenance

program


CV Disease and Risk Management

Pharmacologic treatment to achieve goals of <130/70 mm Hg in older adults is not recommended

Lipid profile if not taking statin: at diabetes diagnosis, at initial medical evaluation, and every 5 years thereafter

Fasting triglyceride levels >500 mg/dL: consider treatment to reduce the risk of pancreatitis

Addition of ezetimibe to moderate-intensity statin therapy may provide additional cardiovascular benefit

– Recent acute coronary syndrome with LDL-C >50 mg/dL

– Cannot tolerate high-intensity statin therapy



CV Disease and Risk Management

Aspirin (75–162 mg/day) for primary prevention in patients at increased risk

– 10-year risk >10%

– Includes men and women >50 years with 1+ major risk factor

Aspirin should not be recommended for patients at low risk

– 10-year risk <5%

– Includes men and women <50 years with no major CV disease risk factors

Clinical judgment for patients with 10-year risk of 5% to 10%


Microvascular Complications

Refer patients for evaluation for renal replacement treatment when eGFR is <30 mL/min/1.73 m2


Older Adults

Assess medical, functional, mental, and social geriatric domains for older diabetics to determine targets and therapeutic approaches

Avoid hypoglycemia: may require adjusting glycemic targets and pharmacological interventions

When palliative care is needed, blood pressure control and intensity of lipid management may be relaxed and therapy adjusted or withdrawn



AACE/ACE CONSENSUS STATEMENT ON THE COMPREHENSIVE TYPE 2 DIABETES (T2D) MANAGEMENT ALGORITHM – 2016

Metformin and B12 Levels

Vitamin B12 levels should be monitored in all patients taking metformin

B12 supplements should be given to affected patients

AACE/ACE Consensus Statement. Endocr Pract. 2016;22(1):84–113.

Blood Pressure Control

<130/80 mm Hg appropriate for most

• Less stringent if frail, complicated comorbidities, or adverse medication effects

• More stringent (e.g., <120/80 mm Hg) if can be reached safely



Lipid Management

High Risk: T2D but no other major risk and/or

age <40 yrs

Very High Risk: T2D (+) >1 major ASCVD risk or established ASCVD

LDL-C (mg/dL) <100 <70

Non-HDL-C (mg/dL) <130 <100

Triglycerides (mg/dL) <150 <150

TC/HDL-C <3.5 <3.0

Apo B (mg/dL) <90 <80

LDL-P (nmol/L) <1,200 <1,000


Insulin Intensification (Prandial Control)

Basal insulin on board but further glycemic control needed:

GLP-1 RA

SGLT2 inhibitor

DPP-4 inhibitor

Prandial insulin

– Basal Plus 1, Plus 2, Plus 3

– 50/50 Basal/Bolus as prandial insulin before each meal based on total daily dose of 0.3–0.5 units/kg


JOINT POSITION STATEMENT OF THE AMERICAN DIABETES ASSOCIATION, THE AMERICAN ASSOCIATION OF DIABETES EDUCATORS, AND THE ACADEMY OF NUTRITION AND DIETETICS


Diabetes Self-Management Education and Support DSME: provision of knowledge and skills necessary to manage

diabetes

– What is diabetes

– How to use a blood glucose meter

– Insulin injection technique

DSMS: support necessary for implementing and maintaining coping skills and behaviors to self-manage the disease

– Refresher courses

– Support groups

– Magazine subscriptionsPowers MA, et al. The Diabetes Educator. 2015;41(4):417–30.

DSME and DSMS for T2D

Powers MA, et al. The Diabetes Educator. 2015;41(4):417–30.

SAFETY COMMUNICATIONS


Multidose Diabetes Pens

“For single patient use only”

www.fda.gov/Drugs/DrugSafety/ucm435271.htm

Repaglinide and Clopidogrel

Clopidogrel inhibits CYP2C8

May inhibit metabolism of repaglinide

Increased risk of hypoglycemia

Concomitant use considered contraindication by Health Canada

www.wolterskluwercdi.com/clinical-notices/special-alerts/

DPP-4 Inhibitors and Joint Pain

New warning and precaution added to labels of all DPP-4 inhibitors

Based on FDA Adverse Event Reporting System database and medical literature

– 33 cases of severe arthralgia (10/16/2006 – 12/31/2013)

– All individuals had decreased level of activity

– 10 required hospitalization for disabling joint pain

Symptoms appeared within 1 day to years after starting medication; most resolved within 1 month of discontinuation

www.fda.gov/Drugs/DrugSafety/ucm459579.htm www.fda.gov/downloads/Drugs/DrugSafety/UCM460038.pdf


Canagliflozin and Bone Fractures

Increased bone fracture associated with canagliflozin

Mean exposure time: 85 weeks

Incidence per 100 patient-years of exposure: – 1.1 (placebo and active comparator)

– 1.4 (canagliflozin 100 mg)

– 1.5 (canagliflozin 300 mg)

Fractures seen as early as 12 weeks of therapy initiation

Mostly due to low trauma (falls from standing height)

Affected upper extremities


Canagliflozin and Bone Mineral Density

Postmarketing safety trial: 714 older individuals with uncontrolled T2DM

– Duration: 2 years

– Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry

Location Canagliflozin 100 mg* Canagliflozin 300 mg*

Total hip 0.9% 1.2%

Lumbar spine 0.3% 0.7%

Femoral neck 0.1% 0.1%

Distal forearm 0% 0.4%

* placebo-corrected decline in BMD


Question of the Day

Based on the available information, should calcium supplementation be recommended to patients who are taking canagliflozin?

Yes No


SGLT2 Inhibitors and Euglycemic DKA

Warning based on 20 cases in the FDA Adverse Event Reporting System database from March 2013 – June 2014

No label change at this time

Factors identified as potential triggers:

– Infection

– Trauma

– Reduced food and fluid intake

– Reduced insulin dosage


SGLT2-Induced Euglycemic Ketoacidosis

↑ urinary glucose

excretion

↑ urinary glucose

excretion

↓ plasma glucose levels

↓ plasma glucose levels

↓ plasma insulin levels

↓ plasma insulin levels

↑ glucagon, lipid oxidation,

and lipolysis

↑ glucagon, lipid oxidation,

and lipolysis

↑ mobilization of FFA and TG

↑ mobilization of FFA and TG

↑ ketogenesis and β-hydroxybutyrate

levels

↑ ketogenesis and β-hydroxybutyrate

levels

Worsened by ↓ insulin and ↓

CHO intake

Worsened by ↓ insulin and ↓

CHO intake

Euglycemic DKAEuglycemic DKA

Rosenstock J, et al. Diabetes Care. 2015;38:1638–42.

CARDIOVASCULAR OUTCOMES STUDIES


Newer Agents for Treatment of T2DM

SAVOR TIMI-53 and EXAMINE Trials

SAVOR TIMI-53 Trial– Hospitalization for heart failure statistically significant (SS) in saxagliptin arm

(3.5% vs 2.8%, HR 1.27, 95% CI 1.07–1.51, P=0.007)

EXAMINE Trial– Increased hospitalizations for heart failure in alogliptin arm; not SS

(3.9% vs 2.8%, HR 1.19, 95% CI 0.90–1.58, P=0.220)

1. Scirica BM, et al. N Engl J Med. 2013;369(14):1317-26.

2. Zannad F, et al. Lancet. 2015;385:2067- 76.

TECOS

14,671 patients from 673 sites in 38 countries

– Type 2 diabetes

– Established CV disease

– >50 years of age

– A1C level 6.5%–8.0%

Sitagliptin or placebo added to current therapy

Median follow-up: 3 years

Green JB, et al. N Engl J Med. 2015;373:232-42.


TECOS: Glycemic Control

A1C mean difference: -0.29% (95% CI, -0.32 to -0.27)

– Sitagliptin group received fewer additional antihyperglycemics (HR, 0.72; 95% CI, 0.68 to 0.77; P<0.001)

– Sitagliptin group less likely to start long-term insulin therapy (HR, 0.70; 95% CI, 0.63 to 0.79; P<0.001)


TECOS: CV Outcomes

Primary composite CV outcome: first confirmed event of CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina –11.4% sitagliptin versus 11.6% placebo

– Non-inferiority: HR, 0.98; 95% CI, 0.88 to 1.09; P<0.001

– Superiority: HR, 0.98; 95% CI, 0.89 to 1.108; P=0.65

Secondary composite CV outcome: first confirmed event of CV death, nonfatal MI, or nonfatal stroke

– Non-inferiority: HR, 0.99; 95% CI, 0.89 to 1.11; P<0.001

– Superiority: HR, 0.99; 95% CI, 0.89 to 1.10; P=0.84


TECOS: Heart Failure

Hospitalization for heart failure

– 3.1% sitagliptin and placebo groups (HR, 1.00; 95% CI, 0.83 to 1.20; P=0.98)

Composite outcome of hospitalization for heart failure or CV death

– 7.3% sitagliptin and 7.2% placebo (HR, 1.02; 95% CI, 0.90 to 1.15; P=0.74)



FDA Advisory Panel Recommendations

Addition of a warning about potential risk for heart failure to:

Saxagliptin-containing products – Safe in general population

– Caution and additional monitoring in patients with eGFR <60 mL/min/1.73 m2 and prior history of heart failure

Alogliptin-containing products– Minor concern for heart failure

– Causal link difficult to establish

www..fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm453900.pdf

GLP-1 RA CV Safety Trials

LEADER: liraglutide

EXSCEL: exenatide

REWIND: dulaglutide

ELIXA: lixisenatide*

*New drug application (NDA) for lixisenatide accepted by FDA and awaiting review. Currently available in Europe, Japan, Australia, and Mexico.

ELIXA

6,068 patients from 49 countries– Type 2 diabetes diagnosis, acute coronary syndrome event within 70 days

– Mean duration of diabetes: 9 years

– Average A1C: 7.6%

– Mean BMI: 30 kg/m2

Lixisenatide or placebo added to current therapy

Study duration: 2 years

www.Medscape.com/viewarticle/846074


ELIXA

Primary composite outcome of CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina: no difference (1.02 HR; 95% CI, 0.89-1.17)

No difference between groups for secondary CV end points

www.Medscape.com/viewarticle/846074

EMPA-REG Outcome

7,020 patients from 590 sites in 42 countries

– Established CV disease

– A1C of 7–9% (no therapy) or 7–10% (stable therapy)

– BMI <45

– eGFR >30 mL/min/1.73 m2

Empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily added

Median study duration: 3.1 years

Zinman B, et al. N Engl J Med. 2015;373(22):2117–28.

EMPA-REG Outcome

Placebo (N=2333)

Empagliflozin(N=4687)

Hazard Ratio (95% CI)

P-Value NNT

Primary Outcome 282 (12.1%) 490 (10.5%) 0.86 (0.74-0.99) 62.5

Noninferiority <0.001

Inferiority 0.04

Secondary Outcome 333(14.3) 599 (12.8) 0.89 (0.78-1.01) 66.7

Noninferiority <0.001

Inferiority <0.08

Death

From any cause 194 (8.3) 269 (5.7) 0.68 (0.57-0.82) <0.001 38.5

From CV causes 137 (5.9) 172 (3.7) 0.62 (0.49-0.77) <0.001 45.5


Noninferiority significance: <0.0249 Superiority significance: <0.0498


EMPA-REG Outcome

Individual CV outcome events were all non-significant, except:

– Hospitalization for heart failure

– Hospitalization for heart failure or death from CV causes (excluding fatal stroke)


Placebo (N=2333)

Empagliflozin(N=4687)

Hazard Ratio (95% CI)

P-Value

Hospitalization for heart failure 95 (4.1) 126 (2.7)0.65

(0.50–0.85)0.002

Hospitalization for heart failure or death from CV causes excluding fatal stroke

198 (8.5) 265 (5.7)0.66

(0.55–0.79)<0.001

EMPA-REG Outcome

Adverse events favoring empagliflozin:

– Any adverse event (P<0.001)

– UTI in female patients (P<0.05)

– Acute kidney injury (P<0.05)

– Acute renal failure (P<0.01)

Adverse events favoring placebo:

– Male and female genital infections (P<0.001)


EMPA-REG Outcome

If not an atherosclerotic benefit, then

HOW???

Benefit in patients without

established CV disease?

Is this a class effect?

What dose of empagliflozin

should be used?

Should empagliflozinbe a “go-to”

agent for patients with ↑ risk for heart

failure?


EMPA-REG Outcome – CKD Patients

Evaluated renal outcomes in patients with T2D and CKD:

– New-onset or worsening nephropathy

– Doubling of serum creatinine (+) eGFR <45 mL/min/1.73 m2

– Initiation of renal replacement therapy

– Death due to renal disease

Brunk D. Clinical Endocrinology News. 2015;10(12):12–15.Wanner C, et al. (Abstract HR-OR01). J Am Soc Nephrol. 2015;26:1133.

Outcome Effect Hazard Ratio

New-onset or worsening

nephropathy

39% decrease in empagliflozin

compared with placebo0.61; P<0.0001

Composite of doubling SCr,

renal replacement initiation,

death due to renal disease

46% decrease in empagliflozin

compared with placebo0.54; P=0.0002

EMPA-REG Outcome – CKD Patients

eGFR <60 eGFR >60

Primary outcome: 3

point major adverse

cardiac events

15% empagliflozin;

16% placebo (HR, 0.88)

9% empagliflozin;


CV death6% empagliflozin;


3% empagliflozin;


Hospitalization for

heart failure

4% empagliflozin;


2% empagliflozin;


All-cause mortality9% empagliflozin;


4% empagliflozin;

7% placebo (HR 0.62)

Brunk D. Clinical Endocrinology News. 2015;10(12):12–15.Wanner C, et al. (Abstract HR-OR01). J Am Soc Nephrol. 2015;26:1133.

Empagliflozin reduces CV morbidity and mortality in patients with T2D and various degrees of CKD

NEW AGENTS


Available Bolus Insulin Options

• Short acting: Regular (Novolin and Humulin R)

• Rapid acting:

• Aspart (NovoLog)

• Lispro (Humalog) **U-100 and U-200

• Glulisine (Apidra)

• Ultra-rapid acting: inhaled (Afrezza)

Lispro U-200

Similar efficacy to lispro U-100

Each 3-mL pen contains 600 units of insulin

No dose conversion between U-100 and U-200

U-100 U-200

Same units of insulin in half the volume of liquid

Fewer insulin pen device changes per week

uspl.lilly.com/humalog/humalog.html#pi

Basal Insulin Options

Intermediate acting: neutral protamine Hagedorn (Novolin and Humulin NPH)

Long acting:

– Detemir (Levemir)

– Glargine U-100 (Lantus)

– Glargine U-100 (Basaglar)

– Glargine U-300 (Toujeo)

– Degludec U-100 and U-200 (Tresiba)


“Follow-on” Insulin Glargine

Received tentative FDA approval in 2014 and final approval in 2015

– Abbreviated approval pathway

– Sufficiently similar to traditional insulin glargine U-100

Available in pen device for adult and pediatric patients with type 1 or type 2 diabetes

www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm477734.htmhttps://investor.lilly.com/releasedetail.cfm?ReleaseID=947336

Glargine U-300

More concentrated: increased dose of insulin in less volume

Flatter and longer profile of action than glargine U-100

– Onset of action: 6 hours

– Maximum glucose lowering effect: up to 5 days

– Once-daily dosing

Less nocturnal hypoglycemia (compared with glargine U-100)

products.sanofi.us/toujeo/toujeo.pdf

Titrate every 5 days!

Glargine U-300

Higher dose of glargine U-300 needed than glargine U-100 to achieve same level of glycemic control

Glargine U-300 stable out of refrigerator for 42 days

products.sanofi.us/toujeo/toujeo.pdfLexicomp Online

Conversion Recommendation

Glargine U-100 to Glargine U-3001:1 conversion, but higher dose of

U-300 will be required

Glargine U-300 to Glargine U-100Use 80% of dose (20% dose

reduction) and adjust as needed


Degludec

Initiation:

• Type 1 (insulin naive): 0.2-0.4

units/kg/day –OR– ⅓ to ½ of total daily

dose (TDD)

• Type 2 (insulin naive): 10 units QD

General Dosing:

• Once daily any time of day

• Doses must be at least 8 hours apart

• No dose conversion between U-100 and

U-200

Titration: every 3-4 daysStable out of refrigerator up to

56 days (8 weeks)

www.novo-pi.com/tresiba.pdf

Basal Insulins

Onset Peak Duration

NPH 2-4 hours 6-10 hours 10-16 hours

Glargine U-100 5 hours NA 20-24 hours

Glargine U-300 6 hours NA 24-36 hours

Detemir 2 hours NA 6-24 hours

Degludec 1 hour NA >42 hours

Pre-Mixed Insulin

Insulin aspart/protamine (Novolog Mix)

Insulin lispro/protamine (Humalog Mix)

Insulin degludec/insulin aspart (Ryzodeg 70/30)


Insulin Degludec/Insulin Aspart

First combination of basal insulin with long duration of action

Once or twice daily dosing

Initiation– T1D (insulin naïve): 50% of total daily dose; give bolus at other meals– T2D (insulin naïve): 10 units once daily

– Conversion from pre-mixed or multiple daily injections: Divide total dose into 2 equal doses

– Once or twice daily basal insulin: unit to unit conversion and maintain dosing schedule

Storage: stable for 28 days out of refrigerator

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002499/WC500139011.pdfwww.accessdata.fda.gov/drugsatfda_docs/label/2015/203313lbl.pdf

Conclusions

The ADA and AACE/ACE differ on the management of diabetes.

DPP-4 inhibitors have been associated with joint pain. Use cautiously in pre-existing joint diseases.

Heart failure associated with DPP-4 inhibitors does not appear to be a class effect.

SGLT2 inhibitors have been associated with euglycemicketoacidosis.

Empagliflozin reduced CV morbidity and mortality in patients with T2DM and CVD.

Available U-200 insulin products are for volume only. No dose conversion needed!

Question 1SGLT2 inhibitors have been associated with:

A. Joint pain

B. Heart failure

C. Euglycemic DKA

D. Worsening albuminuria


Question 2In which disease state should DPP-4 inhibitor treatment be used cautiously?

A. Mild renal impairment

B. Rheumatoid arthritis

C. Recurrent UTI

D. Osteoporosis

Question 3Which was a finding of the treatment arm in the EMPA-REG Outcome Study?

A. Increased incidence of diabetic ketoacidosis

B. Increased incidence of bone fractures

C. Decreased incidence of genital infections

D. Decreased incidence of CV death

Questions?


Attendance Code and Claiming Credit

DM16To obtain CPE credit for participating in this live webinar:

1. Go to:

http://elearning.pharmacist.com/products/4515/diabetes-care-update-2016-live-2-25-16

2. Login using your APhA username and password

3. Click “Enroll Now” button to begin the assessment and evaluation

4. Once you have successfully completed the assessment and evaluation, you may then claim credit. You must claim credit for attending the live webinar by March 25, 2016.


http://elearning.pharmacist.com/products/4515/diabetes-care-update-2016-live-2-25-16

Documents

Diabetes Care Update 2016elearning.pharmacist.com/.../Diabetes_Update_2016_HANDOUT_021… · Diabetes Care Update 2016, is approved for 1 hour of continuing pharmacy education credit