powerpoint presentation · insulin 35 inhaled insulin •inhaled insulin—afrezza® regular...

4/1/2016

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What’s New in Diabetes Medications

Jena Torpin, PharmD

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• Discuss new medications in the management of diabetes

• Understand the mechanism of the medications discussed

• Understand the side effects of the medications discussed

Objectives

Acknowledgement: Some slides adapted/used with permission from

Dr. Heather Blue’s Presentation, Diabetes Medication Update, 3/5/2015

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•Types of Diabeteso Type 1: complete insulin deficiencyo Type 2: decreased insulin secretion & insulin resistance

Review of Diabetes

Cefalu, Diabetes Care, 2016; Khardori R, www.Medscape.org, 2015

Hepatic Glucose Production

Peripheral Glucose Uptake

Pancreatic Insulin secretion

Blood

Glucose

http://www.medscape.org/

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Review of Diabetes- Diagnosis

Test Dx Criteria

Fasting Plasma Glucose (FPG) ≥ 126 mg/dL

2 Hour Plasma Glucose ≥ 200 mg/dL

A1C ≥ 6.5%

Random Glucose ≥ 200 mg/dL + symptoms of

hyperglycemia/crisis

Cefalu, Diabetes Care, 2016; Khardori R, www.Medscape.org, 2015

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Review of Diabetes-Goals

Patient population A1C Goal (%)

Most adults (non-pregnant) ≤ 7

Select patients (low risk for hypoglycemic events) ≤ 6.5

Select patients (high risk for hypoglycemic events,

advanced age, vascular complications)

≤ 8

Cefalu, Diabetes Care, 2016

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Review of Diabetes- Treatment of Type 2 Diabetes

2nd Line1st Line

Metformin

Oral Agent

GLP-1 Analog

Insulin

• Sulfonylurea

• Thiazolidinedione

• DPP-4 Inhibitor

• SGLT2 Inhibitor

Cefalu, Diabetes Care, 2016


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•Metformin•Sulfonylureas•Thiazolidinediones•Insulin•Meglitinides•Alpha-glucosidase inhibitors

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Previous Toolbox

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•Effectiveness: Decreases A1C by 1-1.5%

•Dosing: titrate to goal 1000mg BID or 2000mg qday if ER

•Adverse Drug Events: GI Side (need to titrate/take with food), Vitamin B12 deficiency, lactic acidosis (rare)

•Cost: $4 list

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Previous Toolbox- Biguanide (Metformin)

Hepatic Glucose

Production

Insulin Sensitivity•Mechanism:

Cefalu, Diabetes Care, 2016; UpToDate; Bahal O’Mara, Pharmacist’s Letter, 2015

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•Mechanism of Action: pancreatic release of insulin


•Dosing: Start low and go slow in elderly patients and those with hepatic or renal disease

•Adverse Drug Events: hypoglycemia

•Cost: $4 list

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Previous Toolbox- Sulfonylureas (Glyburide, Glipizide, Glimepiride)

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015

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•Mechanism of Action: Increased insulin sensitivity


•Dosing: titrate cautiously- monitor for signs of heart failure

•Adverse Drug Events: Edema, heart failure, fractures, increased LDL (rosiglitazone)

•Cost: Low

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Previous Toolbox- Thiazolidinediones (TZDS- Pioglitazone, Rosiglitazone)

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015; UpToDate

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Previous Toolbox-Insulin

Micromedex, Lexicomp, UpToDate

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Previous Toolbox-Insulin Profiles

Micromedex, Lexicomp, UpToDate

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Previous Toolbox

Metformin Sulfonylurea TZD Insulin

Efficacy/A1C

reduction

High: 1-1.5% High: 1-1.5% High: 1-1.5% Highest: 1.5-

3.5%

Hypoglycemia

Risk

Low Moderate Low High

Weight Neutral Gain Gain Gain

Side Effects GI, lactic

acidosis (rare)

Hypoglycemia Edema, Heart

failure,

fractures

Hypoglycemia

Costs Low- $4 list Low- $4 list Low Variable


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• Sodium-glucose cotransporter 2 (SGLT2) Inhibitors

• Dipeptidyl pepidase-4 (DPP-4) Inhibitors (gliptins)

• Injectable glucagon-like peptide 1 (GLP-1) receptor agonists

• New insulin formulations-Inhaled insulin-New concentrations

New Diabetes Medications

Sodium Glucose

Co-Transporter 2

Inhibitors

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•Drugs:o canagliflozin (Invokana®)o dapagliflozin (Farxiga®)o empagliflozin (Jardiance®)

•Mechanism: Prevents glucose from being reabsorbed by kidneys, resulting in glucose loss into urine

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Sodium-glucose transporter 2

inhibitors


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•Reduced A1c by 0.5-1% points

•Weight loss seen in trials (up to 4.5 kg)

•Reduction of blood pressure (up to 7 mmHg)

•No hypoglycemia

•Decreased CVD events/mortality in pt’s with CVD

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Effectiveness of SGLT2 Inhibitors

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015; Nauck, Drug Des Devel

Ther, 2014

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Dosing of SGLT2 Inhibitors

canagliflozin dapagliflozin empagliflozin

Usual adult dose

GFR >60

mL/min/1.73 m(2)

100mg

300mg daily

5mg 10mg

daily

10mg 25mg

daily

GFR 45-60

mL/min/1.73 m(2)

Limit dose at

100mg daily

Do not use 10mg 25mg

daily

GFR <45

mL/min/1.73 m(2)

Do not use Do not use Do not use

Micromedex

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•Urinary tract infections (~5%)•Genital infections (up to ~11%)•Renal impairment•Polyuria (~5%)•Hypovolemia•Increased LDL•Bladder cancer?

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Adverse Effects of SGLT2 Inhibitors

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015; Micromedex, UpToDate

Dipeptidyl

Peptidase-4

Inhibitors

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Dipeptidyl Peptidase-4 Inhibitors

•Drugs:o sitagliptin (Januvia®)o saxagliptin (Onglyza®)o linagliptin (Tradjenta®)o alogliptan (Nesina®)

•Mechanism: Inhibit dipeptidyl peptidase-4 which is an enzyme which breaks down endogenous incretins o e.g. glucagon like peptide 1 (GLP-1)


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Insulin Secretion/Synthesis

Glucagon secretion

Henry RR, www.medscape.org, 2009

Endogenous Incretin Mechanism of Action

23Image: Adapted from Henry RR, www.medscape.org, 2009

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•Reduced A1C by 0.5-1%; some believe to more around ≤ 0.7%

•No hypoglycemia (monotherapy)

•Weight neutral

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Effectiveness of DPP-4 Inhibitors




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Dosing of DPP-4 Inhibitors

sitagliptin saxagliptin linagliptin alogliptin

Usual dose 100 mg daily 2.5-5 mg daily 5 mg daily 25 mg daily

Renal CrCl 30-50

50 mg daily

CrCl <30 25

mg daily

CrCl

<50ml/min

2.5 mg daily

No

adjustments

needed

30-60

12.5 mg daily

<306.25 mg

daily

UpToDate

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•Potential for pancreatitis

•May increase risk of hospitalizations due to heart failure

•Immune –mediated dermatological/angioedema side effects

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Adverse Effects of DPP4-Inhbitors


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Glucagon-Like

Peptide-1 (GLP-1)

Agonist

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•Short Actingo Exenatide (Byetta®)-- twice dailyo Liraglutide (Victoza®) -- once daily

•Long Acting—Weekly dosingo Albiglutide (Tanzeum®) o Exenatide extended release (Bydureon®) o Dulaglutide (Trulicity®)

• Mechanism: bind to GLP-1 receptors

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Glucagon-like peptide 1 receptor agonists


29Image: Adapted from Henry RR, www.medscape.org, 2009

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Effectiveness

• Reduced A1C by 1-1.5%

•Few/no hypoglycemic events (monotherapy)

•Weight loss (~1-2.7kg)

•Some CV risk reduction

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015; Micromedex


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Dosing

Exenatide Liraglutide

Usual dose 5 mcg 10 mcg SubQ BID 0.6 mg 1.2-1.8mg SubQ

qday

Renal CrCl 30-50 mL/min: use caution

CrCl <30 mL/min: not recommended

No adjustment needed

Exenatide (extended

release)

Albiglutide Dulaglutide

Usual

dose

2mg SubQ qWeek 30 mg 50 mg SubQ

qWeek

0.75mg 1.5mg

SubQ qWeek

Renal CrCl 30-50 mL/min: use

caution

CrCl <30 mL/min: not

recommended

No adjustments needed No adjustment

needed (use with

caution)

UpToDate,

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•Boxed warning: thyroid C-cell tumors

•GI Side Effects: Nausea/vomiting/diarrhea: 10-50%

•Potential for pancreatitis

•Renal dysfunction

•Injection site reactions

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Adverse effects of Glucagon-like peptide 1 receptor agonists

Cefalu, Diabetes Care, 2016; Bahal O’Mara, Pharmacist’s Letter, 2015; Micromedex

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New Diabetes Medications

DPP-4 Inhibitor SGLT2 Inhibitor GLP-1 Receptor Agonist

Efficacy/A1C

reduction

Intermediate: 0.5-

1%

Intermediate: 0.5-

1%

High: 1-1.5%

Hypoglycemia

Risk

Low Low Low

Weight Neutral Loss Loss

Side Effects Rare Genitourinary,

dehydration

GI

Costs High High High


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Insulin

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Inhaled Insulin

•Inhaled insulin—Afrezza® regular insulin•4 unit, 8 unit, and 12 unit cartridges

•Dosing:

•Side Effects: hypoglycemia, cough, throat pain

Afrezza®, Prescribing Information, 2014

Injected Prandial Insulin Afrezza Dose

Up to 4 units 4 units

5-8 units 8 units

9-12 units 12 units

13-16 units 16 units



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•Lispro (Humalog KwikPen): 200 units/mL

•Glargine (Toujeo SoloStar): 300 units/mL

•Degludec (Tresiba FlexTouch): 100 units/mL &

200 units/mL

•Degludec/aspart 70/30 (Ryzodeg 70/30): 100

units/mL

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Other/New Insulin Formulations

UpToDate

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Take Away Points

•Many new medications with novel mechanisms

•Mainstay of therapy while patients are in the hospital still remains insulin therapy

[email protected]

thank you!

powerpoint presentation · insulin 35 inhaled insulin •inhaled insulin—afrezza® regular...

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