7/23/2015
Financial Disclosures
David Matthews has no relevant financial relationship(s) with any commercial interest(s) to disclose.
Diabetes Update 2015
David E. Matthews, PharmD
Assistant Professor
Department of Pharmacy Practice
Shenandoah University Bernard J. Dunn School of Pharmacy
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Objectives
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Objectives, Continued
• Review the most recent recommendations for diabetes management according to the 2015 American Diabetes Association (ADA), including management of common comorbidities
• Discuss the efficacy, safety, and place in therapy for newly‐approved non‐insulin anti‐
diabetic medications
• Discuss recent developments in insulin therapy, including concentrated insulin products, biosimilar products, and novel routes of administration
• Given a patient case, apply information related to recent developments in diabetes management to provide optimal care
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Presentation Outline
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Patient Case
Diabetes pathophysiology review
Approach to therapy: 2015 ADA Guidelines
Recent advances in non‐insulin therapies
Recent advances in insulin therapies
Patient case
RS is a 54 year old white female who presents to your community pharmacy for a medication therapy management (MTM) visit. She is feeling well, but says she is disappointed that she has been unable to control her diabetes adequately. She was told by her physician at a recent visit that her A1c is 8.4%.
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7/23/2015
Patient Case, Continued
Patient Case, Continued
PMH: T2DM, HTN
SH: non‐smoker, EtOH 1‐2 times per week
FH: Father died of MI at age 55, had DM
Mother died of lung CA at age 78
Blood glucose log over past week:
Date
Pre‐breakfast
(fasting)
Bedtime
(~2hr post‐dinner)
BP today: 138/88, right arm, seated
7/19
7/20
156
168
251
Medication list:
• Metformin 500 mg BID
• Lisinopril 40 mg once daily
• HCTZ 25 mg once daily
• Januvia 100 mg once daily
• Glipizide 10 mg BID
7/21
128
279
7/22
133
240
7/23
170
7/24
7/25
192
155
301
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Patient Case, Continued
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Patient Case: Questions
RS has a prescription for a new medication today:
• How would you assess RS’s current control of her diabetes? What are her goals?
• What changes could you suggest making to RS’s physician after your MTM session?
• Is the new prescription for RS appropriate?
• Would any other new agents be appropriate?
• What counseling points would be appropriate for RS?
Bydureon pen 2mg, inject subQ once weekly
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DM Pathophysiology
DIABETES PATHOPHYSIOLOGY: REVIEW
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7/23/2015
Diagnosis
Glycemic Targets
Any of the following:
• A1c >6.5%*
• Fasting blood glucose (FBG) >126 mg/dL*
• 2hr post‐prandial BG >200 mg/dL following oral glucose tolerance test (OGTT)*
• Random plasma glucose >200 in the presence of classic hyperglycemic symptoms
• A1c <7% for most patients*
• Fasting BG 80‐130 mg/dL*
• Previously 70‐130 mg/dL
• Peak post‐prandial BG <180 mg/dL*
*All goals should be individualized
*In the absence of unequivocal hyperglycemia, must be repeated for confirmation of diagnosis
• Disease duration, life expectancy, comorbidities, risk of hypoglycemia, support system, etc.
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Approach to Therapy: ADA2015
• Lifestyle modification for all
• Metformin preferred initial therapy
• If no contraindications or intolerance
• Add second agent if needed after 3 months
• Tailor to patient‐specific factors
• Add third agent if needed after 3 months
• Tailor to patient‐specific factors
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Approach to Therapy: ADA2015
• Consider starting with dual therapy if A1c >9%
• Consider starting with insulin if:
• BG >300
• A1c >10%
• Catabolic features present
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Diabetes Care. 2015 Jan;38 Supp 1: S1‐S93
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7/23/2015
Hypertension in DM
Cardioprotection in DM
• BP Goal for most diabetic patients 140/90
• Specific LDL target no longer recommended
• Statins recommended for most diabetics
• Change from 140/80 in 2014 Guidelines
• Lower goals may be acceptable in some patients
• ACE or ARB first line due to nephroprotection
BP Goal
JNC 8
ADA 2015 ADA 2014 ADA 2013
140/90
140/90
140/80
• Decrease risk of CV events
• Choice of statin based on patient‐specific factors
• Overt cardiovascular disease / CV risk factors
• Age
• Tolerability
130/80
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Classification of Statins
• Based on percentage of LDL lowering
High Intensity
(LDL lowering >50%)
Moderate Intensity
(LDL lowering 30‐50%)
Low‐Intensity
(LDL lowering <30%)
Atorvastatin 40*‐80 mg
Atorvastatin 10‐20 mg
Pravastatin 10‐20 mg
Rosuvastatin 20‐40 mg
Rosuvastatin 10 mg
Lovastatin 20 mg
Simvastatin 20‐40 mg
Pravastatin 40 mg
Lovastatin 40 mg
Diabetes Care. 2015 Jan;38 Supp 1: S1‐S93
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Immunizations
Pneumococcal Update
• Pneumococcal polysaccharide vaccine (PPSV23)
• Influenza annually for patients >6 mo. • Pneumococcal vaccination (PCV13 / PPSV23)
• First dose >2yo
• Second dose >65yo
• Minimum 5 years between doses
• See next slide
• Hepatitis B series
• Pneumococcal conjugate vaccine (PCV13)
• Recommended for ages 19‐59
• Consider for age >60
• Now recommended for all adults >65yo
• Adults >65yo should receive PCV13 first, then PPSV23 6‐12 months later
• If already received PPSV23, give PCV13 12 months later
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7/23/2015
Summary of Major Changes
• Fasting blood glucose goal now 80‐130 mg/dL
• (previously 70‐130 mg/dL)
RECENT ADVANCES:
NON‐INSULIN THERAPIES
• BP goal now <140/90
• (previously <140/80)
• Lipid goal now risk‐based similar to 2013 ACC/AHA guidelines
• (previously targeted LDL levels)
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Non‐Insulin Anti‐Diabetic Agents
SGLT‐2s: Available Agents
• Most recently approved therapies
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• SGLT‐2 inhibitors
• GLP‐1 agonists • Daily or twice daily
• Once weekly
Canagliflozin (Invokana®)
Dapagliflozin (Farxiga®)
Empagliflozin (Jardiance®)
Others under investigation
www.invokana.com/
• DPP‐4 inhibitors
https://www.farxiga.com/
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SGLT‐2 Inhibitors: MOA
https://www.jardiance.com/
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SGLT‐2 Inhibitors: MOA
• SGLT = sodium‐glucose transport protein
• Expressed in kidney and promotes glucose reabsorption
• SGLT‐2 is responsible for ~90% of glucose reabsorption in the kidney
• Inhibition leads to increased glucose excretion in the urine
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SGLT2 inhibitor
SGLT2 inhibitor
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7/23/2015
SGLT‐2 Inhibitors
SGLT‐2s: “The Good” • Do not use in:
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• Renal impairment
• Patients predisposed to side effects (use caution)
May decrease BP
Weight loss
Once daily PO
Rarely cause hypoglycemia
More potent than DPP‐4 Inhibitors
• A1c lowering ~1%
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SGLT‐2s: “The Bad” SGLT‐2s: Place in Therapy
• Lack long‐term safety data
• Increase LDL
• Side effects
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• Consider as add‐on therapy AFTER usual second‐line options
• Patients who decline insulin who need additional oral therapy
• Patients at low risk of side effects
Urinary tract and genital yeast infections
Hyperkalemia
Hypotension
Ketoacidosis?
• Cost
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GLP‐1 Agonists: Available Agents
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The Incretin Effect
• Agents given once or twice daily
• Exenatide (Byetta®)—twice daily before meals
• Liraglutide (Victoza®)—once daily
• Agents given once weekly
• Exenatide extended release (Bydureon®)
• Albiglutide (Tanzeum®)
• Dulaglutide (Trulicity®)
https://www.trulicity.com/
https://www.byetta.com/
www.victoza.com/
https://bydureon.com/
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http://www.tanzeum.com/
http://www.medscape.org/viewarticle/702364
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7/23/2015
GLP‐1 Agonists: MOA
GLP‐1 Agonists
• Mimics endogenous glucagon‐like peptide‐1
• Do not use in:
• History of pancreatitis
• History of thyroid carcinoma
• Gastroparesis
• Effect on BG:
• Shortest acting agent (Byetta®) mostly post‐prandial
• Weekly agents affect fasting AND post‐prandial readings
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GLP‐1 Administration
GLP‐1s: “The Good”
• Byetta® and Victoza®: pen injector
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• Prime prior to first use only
• Byetta® before meals; Victoza without regard to meals
• Bydureon®: vial for reconstitution OR pen
• Tanzeum® and Trulicity®: pen injector
• Trulicity® pen requires no mixing Weight loss
Relatively potent “Glucose‐dependent” action
Synergistic with insulin
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GLP‐1s: “The Bad”
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GLP‐1s: Place in Therapy
GI Upset
Injection only
Pancreatitis / thyroid tumors?
Cost
• Add‐on therapy to metformin
• Patients within 1‐1.5% of A1c goal
• In combination with insulin (unlabeled but common)
• Patients who desire weight loss or have concerns regarding weight gain with insulin
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7/23/2015
DPP‐4 Inhibitors: Available Agents
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DPP‐4 Inhibitors: MOA
Sitagliptin (Januvia®)
Saxagliptin (Onglyza®)
Linagliptin (Tradjenta®)
Alogliptin (Nesina®)
Combination products (with metformin, sulfonylureas etc.)
www.januvia.com/
https://www.onglyza.com/
https://www.tradjenta.com/
• Dipeptidyl peptidase 4 (DPP‐4) is an enzyme that breaks down GLP‐1
• Inhibition of DPP‐4 increases levels of endogenous GLP‐1 by preventing breakdown
• End result = enhanced incretin effect in response to a meal
• Affects only post‐prandial BG
www.nesina.com/
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DPP‐4 Inhibitors: MOA
DPP‐4s: “The Good”
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Usually well tolerated
Weight neutral
Does not cause hypoglycemia
Once daily PO
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DPP‐4s: “The Bad”
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DPP‐4s: Place in Therapy
• Not very potent and only affects post‐prandial blood glucose
• Heart failure?
• Pancreatitis (rare)
• Little to no effect on fasting BG
• Cost
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• Add‐on to be considered after metformin / possibly other oral agents
• Patient with elevated post‐prandial readings who is otherwise near goal
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7/23/2015
Developments in Insulin Therapy
• Concentrated insulin • Insulin glargine U‐300 (Toujeo®)
• Insulin lispro U‐200 (Humalog U‐200®)
RECENT ADVANCES:
INSULIN THERAPIES
• Biosimilar products (on the horizon)
• Inhaled insulin (Afrezza®)
• Disposable insulin delivery systems (V‐Go®)
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Insulin Glargine U‐300 (Toujeo®)
Toujeo® vs. Lantus®
• What it is:
• Non‐inferior in terms of A1c reduction
• No difference in overall hypoglycemic events
• Significantly fewer episodes of nocturnal hypoglycemia
• Patients on Toujeo® required 10‐17% more insulin to maintain glycemic control
• Concentrated version of Lantus® that allows for small injection volume
• Slower onset and longer duration than Lantus®
• May cause less nocturnal hypoglycemia
• What it IS NOT:
• Substitute for Humulin U‐500 in patients requiring high dose insulin
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Toujeo® Solostar® Pen
Insulin Lispro U‐200 (Humalog®)
• Administration similar to Lantus® Solostar®
• 1 pen = 450 units
• 1 box = 3 pens = 1350 units
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• Compared to 1500 units for Lantus® Solostar®
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Approved late May 2015
Comes in Kwikpen® device (same as U‐100)
1 pen = 600 units
Marketed by Eli Lilly as a method to reduce the need for frequently switching pens
http://www.humalog.com/
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7/23/2015
Biosimilar Agents
Biosimilar Pathway for Approval
• January 2014: Eli Lilly’s application for glargine
biosimilar blocked by Sanofi lawsuit
• August 2014: FDA tentatively approves glargine
biosimilar pending outcome of lawsuit
• September 2014: EC approves glargine biosimilar in Europe
• March 2015: FDA approves first biosimilar in US market (Zarxio®, biosimilar to filgrastim)
• August‐September 2015: Anticipated launch of glargine biosimilar in Europe
• Future: ??????
• Products derived from living organisms have interbatch variability no “generics”
• FDA created pathway for approval of “biosimilar” agents
• Biosimilar vs. interchangable
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Inhaled Insulin (Afrezza®)
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Afrezza® Inhaler
• Inhaled insulin was previously available as Exubera® (Pfizer) but discontinued in 2007
• Concept reintroduced in 2015 by Sanofi under the name Afrezza®
• Smaller inhaler with easier administration
www.afrezza.com/
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Afrezza® Inhalation
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Afrezza® Components
Open inhaler and insert cartridge; keep level
Lower mouthpiece to close inhaler
Exhale completely
Place mouthpiece in mouth, tilt inhaler down slightly toward chin
• Inhale deeply, hold breath as long as comfortable before exhaling
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• Each Rx comes with 2 inhalers
• Each inhaler lasts 15 days
• Each package = 3 foil packs
• Each foil pack = 2 blister cards with 15 cartridges
• Cartridges in groups of 3 per blister
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7/23/2015
Afrezza® Storage
• Unopened: refrigerate (cartridge should be at room temp for 10 min before use)
• Opened foil pack
• Good for 10 days at room temperature
• Opened blister (group of 3 cartridges)
• Good for 3 days at room temperature
• Inhaler device
• Good for 15 days
http://www.healthline.com/diabetesmine/test‐driving‐new‐inhaled‐insulin‐afrezza
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Afrezza®: “The Good”
Afrezza®: “The Bad”
• Option for patients who dislike multiple daily injections
• Relatively easy administration compared to predecessor product
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Confusing storage requirements
Must be dosed in 4 unit increments
Cough common
Possible decrease in lung function
• Spirometry required at baseline, 6 months, then annually during therapy
• Cost
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Novel Delivery Devices
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V‐Go® system
• V‐Go® disposable insulin delivery system
• “Patch pump” system replaced each day
• Releases rapid acting insulin (lispro or aspart) at slow controlled “basal” rate
• 20, 30, or 40 units/day
• Ability to “bolus” increments of 2 units at mealtime
• Maximum 36 bolus units per 24 hours
• 1 click = 2 units
http://www.go‐vgo.com/
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V‐Go® System
V‐Go® System
• A new patch must be prepared each day
• A new patch must be prepared each day
http://www.go‐vgo.com/sites/default/files/upload/patient‐start‐guide.pdf
http://www.go‐vgo.com/sites/default/files/upload/patient‐start‐guide.pdf
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V‐Go® System: “The Good”
V‐Go® System: “The Bad”
• Option for patients who need prandial coverage but do not want or refuse to give multiple daily injections
• Small and discreet
• Patient’s insulin requirements must match system’s capabilities:
• Basal rate limited to 20, 30, or 40 units/day
• Bolus max of 36 units/day
• Must prepare new patch each day, somewhat complicated
• Cost
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Patient Case
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Patient Case, Continued
RS is a 54 year old white female who presents to your community pharmacy for an MTM visit. She is feeling well, but says she is disappointed that she has been unable to control her diabetes adequately. She was told by her physician at a recent visit that her A1c is 8.4%.
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PMH: T2DM, HTN
SH: non‐smoker, EtOH 1‐2 times per week
FH: Father died of MI at age 55, had DM
Mother died of lung CA at age 78
BP today: 138/88, right arm, seated
Medication list:
• Metformin 500 mg BID
• Lisinopril 40 mg once daily
• HCTZ 25 mg once daily
• Januvia 100 mg once daily
• Glipizide 10 mg BID
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7/23/2015
Patient Case, Continued
Patient Case, Continued
Blood glucose log over past week:
Date
Pre‐breakfast
(fasting)
Bedtime
(~2hr post‐dinner)
7/19
7/20
156
168
251
7/21
128
279
7/22
133
240
7/23
170
7/24
7/25
192
155
RS has a prescription for a new medication today:
Bydureon pen 2mg, inject subQ once weekly
301
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Patient Case: Questions
Thank You for Coming!
• How would you assess RS’s current control of her diabetes? What are her goals?
• What changes could you suggest making to RS’s physician after your MTM session?
• Is the new prescription for RS appropriate?
• Would any other new agents be appropriate?
• What counseling points would be appropriate for RS?
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Afrezza® [package insert]. Bridgewater, NJ: Sanofi; 2015.
American Diabetes Association. Standards of medical care in diabetes—2015. Diabetes Care. 2015;38(suppl1):S1‐S93.
Baruah MP, Kalra S.. The novel use of GLP‐1 analogue and insulin combination in type 2 diabetes mellitus. Recent Pat Endocr Metab
Immune Drug Discov. 2012 May;6(2):129‐35.
Bydureon® [package insert]. Wilmington, DE: AstraZeneca; 2015.
Byetta® [package insert]. Wilmington, DE: AstraZeneca; 2015.
Centers for Disease Control and Prevention PCV13 (Pneumococcal Conjugate Vaccine). Accessed July 22, 2015.
Farxiga® [package insert]. Wilmington, DE: AstraZeneca; 2015.
Humalog® [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2015.
Januvia® [package insert]. Kenilworth, NJ: Merck and Company; 2015.
Jardiance® [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
PL Detail‐Document, Comparison of Insulins and Injectable Diabetes Meds. Pharmacist’s Letter/Prescriber’s Letter. March 2015.
Riddle MC, Yki‐Järvinen H, Bolli GB, Ziemen M, Muehlen‐Bartmer I, Cissokho S, Home PD. One‐year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal‐
time insulin: the EDITION 1 12‐month randomized trial, including 6‐month extension. Diabetes Obes Metab. 2015 Apr 2. Role of the Inhaled Insulin, Afrezza, for Diabetes. Pharmacist's Letter 2015; 31:
SGLT2 Inhibitors (Flozins) and Risk of Ketoacidosis. Pharmacist's Letter 2015; 31(7):310704. Accessed July 22, 2015.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation. Published online November 12, 2013.
Tanzeum® [package insert]. Philadelphia, PA; GlaxoSmithKline; 2015.
Toujeo® [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
Tradjenta® [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
Trulicity® [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
Victoza® [package insert]. Plainsboro, NJ: Novo Nordisk, Inc,; 2015.
Winter A, Lintner M, Knezevich E. V‐Go Insulin Delivery System Versus Multiple Daily Insulin Injections for Patients With Uncontrolled Type 2 Diabetes Mellitus. J Diabetes Sci Technol. 2015 Apr 21.
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Diabetes Update 2015
David E. Matthews, PharmD
Assistant Professor
Department of Pharmacy Practice
Shenandoah University Bernard J. Dunn School of Pharmacy
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