Hyperglycemia Management –

Medication TherapyJanice Frueh, PharmD, BCPSAssociate Clinical Professor

SIUE School of Pharmacy

June 2nd , 2015

Objectives

• Compare and contrast differences in the physiologic effects for glucose control of newer anti-hyperglycemia medications

• Describe important considerations for effective and safe use of newer anti-hyperglycemia medications and medication delivery devices

Diabetes Self-

Management Education and

Support=

The City of New York. http://www.nyc.gov/html/doh/html/hcp/diabetes-provider-kit.shtml. Accessed on May 2015

Oral & non-insulin injectable medications

Class Agent(s) Available as-Glucosidase inhibitors

AcarboseMiglitol

Precose or genericGlyset

Amylin analogue Pramlintide Symlin

Biguanide Metformin Glucophage or generic

Bile acid sequestrant Colesevelam WelChol

DPP-4 inhibitorsAlogliptinLinagliptinSaxagliptinSitagliptin

NesinaTradjentaOnglyzaJanuvia

Dopamine-2 agonist Bromocriptine Cycloset

Glinides NateglinideRepaglinide

Starlix or genericPrandin

Class Agent(s) Available as

GLP-1 receptor agonists

AlbiglutideDulaglutideExenatideExenatide XRLiraglutide

TanzeumTrulicityByettaBydureonVictoza

SGLT2 inhibitorsCanagliflozinDapagliflozinEmpagliflozin

InvokanaFarxigaJardiance

Sulfonylureas

GlimepirideGlipizideGlyburide

Amaryl or genericGlucotrol or genericDiaeta, Glynase, Micronase, or generic

Thiazolidinediones PioglitazoneRosiglitazone

Actos or geneticAvandia

DPP-4 = dipeptidyl peptidase; GLP-1 = glucagon-like peptide; SGLT2 = sodium glucose cotransporter 2.

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379..

Insulin medications and delivery devices

V-Go® Insulin Delivery SystemAgent Available as

Basal

NPH

Glargine U-100Glargine U-300Detemir

Lantus (Pen = SoloSTAR)

Levemir (Pen=FlexTouch)

Basal-Prandial

Regular U-500

Prandial

Regular Humulin RNovlooin R

AspartGlulisineLispro

Novolog (Pen=FlexPen)Apidra (Pen = SoloSTAR)Humalog (Pen=KwikPen)

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

Picture from Valertiras. http://www.go-vgo.com/what-is-vgo. Accessed on March 2015

Picture from Sanofi-Aventis. https://www.afrezza.com. Accessed on May 2015

Afrezza ® Inhaled Insulin

Antihyperglycemic therapy in type 2 diabetes: general recommendations.

Silvio E. Inzucchi et al. Type 2 DM Antihyperglycemic Therapy: General Recommendations Diabetes Care 2015;38:140-149

Antihyperglycemic therapy in type 2 diabetes: general recommendations.

Silvio E. Inzucchi et al. Dia Care 2015;38:140-149©2015 by American Diabetes Association

At 3 month f/u = 6 choices for medication management

Silvio E. Inzucchi et al. Type 2 DM Antihyperglycemic Therapy: General Recommendations Diabetes Care 2015;38:140-149

Antihyperglycemic therapy in type 2 diabetes: general recommendations.

At 3 month f/u =LOTS of choices for medication management

Silvio E. Inzucchi et al. Type 2 DM Antihyperglycemic Therapy: General Recommendations Diabetes Care 2015;38:140-149

PATIENT TAKE HOME MESSAGE: Individualized Approach to Blood Sugar

Control Targets

•Medication management of hyperglycemia focuses on:-Efficacy (how much the A1c decreases)-Hypoglycemia risk (patient AND medication risk factors)-Impact on weight-Other side effects-Cost

Silvio E. Inzucchi et al. Type 2 DM Antihyperglycemic Therapy: General Recommendations Diabetes Care 2015;38:140-149

Normal Glucose Levels

Liver Kidney

Non-insulin dependent

• Brain• Neurons

Insulin dependent

• Liver• Muscle

Eliminate Glucose

Produce Glucose

Triplitt CL, Repas T, and Alvarez C. Diabetes. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy, 9th ed. New York: McGraw-Hill; 2014. Accessed Online: http://accesspharmacy.mhmedical.com.libproxy.siue.edu/ May 2015.

Hyperglycemia Pathophysiology: Type 2 DM

Impairments in Glucose Regulation Medications Impacting Glucose Regulation

Impaired insulin secretion Deficient insulin release Decrease in beta-cell mass +/- function

Sulfonylureas

Insulin resistance Muscle cells have impaired intracellular regulation Liver cells are less responsive to insulin and

inadequately suppress glucagon levels

MetforminThiazolidinediones

Blunted incretin effect GLP-1 receptor agonistsDPP-4 inhibitors

DPP-4 = dipeptidyl peptidase; GLP-1 = glucagon-like peptide;

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379..

Triplitt CL, Repas T, and Alvarez C. Diabetes. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy, 9th ed. New York: McGraw-Hill; 2014. Accessed Online: http://accesspharmacy.mhmedical.com.libproxy.siue.edu/ May 2015.

Oral & non-insulin injectable medications

Class Agent(s) Available as-Glucosidase inhibitors

AcarboseMiglitol

Precose or genericGlyset

Amylin analogue Pramlintide Symlin

Biguanide Metformin Glucophage or generic

Bile acid sequestrant Colesevelam WelChol

DPP-4 inhibitorsAlogliptinLinagliptinSaxagliptinSitagliptin

NesinaTradjentaOnglyzaJanuvia

Dopamine-2 agonist Bromocriptine Cycloset

Glinides NateglinideRepaglinide

Starlix or genericPrandin

DPP-4 = dipeptidyl peptidase; GLP-1 = glucagon-like peptide; SGLT2 = sodium glucose cotransporter 2.

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379..

Class Agent(s) Available as

GLP-1 receptor agonists

AlbiglutideDulaglutideExenatideExenatide XRLiraglutide

TanzeumTrulicityByettaBydureonVictoza

SGLT2 inhibitorsCanagliflozinDapagliflozinEmpagliflozin

InvokanaFarxigaJardiance

Sulfonylureas

GlimepirideGlipizideGlyburide

Amaryl or genericGlucotrol or genericDiaeta, Glynase, Micronase, or generic

Thiazolidinediones PioglitazoneRosiglitazone

Actos or geneticAvandia

GLP-1 Agonists

Take Home Points: GLP-1 receptor agonists Efficacy: ~1% A1c reduction

- Impact post-prandial glucose- 4 -10 weeks for maximum glucose

lowering effects

Impact on weight: Neutral or Loss

Other Side Effects/Concerns: - Thyroid carcinoma - Acute pancreatitis- Gastroparesis- Narrow therapeutic index

medications

Triplitt CL, Repas T, and Alvarez C. Diabetes. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy, 9th ed. New York: McGraw-Hill; 2014. Accessed Online: http://accesspharmacy.mhmedical.com.libproxy.siue.edu/ May 2015.

Take Home Points: GLP-1 receptor agonists • Short-acting dosage formulations

• Exenatide: Take with a meal. Skip dose if usual meal missed

• Long-acting dosage formulations• Common side effect: palpable nodule, erythema at injection site. • No dependence on meals• If dose is missed, take within 3 days of usual administration day . HAVE 2

ROUTINE ADHERENCE METHODS. • Exenatide, Albiglutide: May need up to 30-60 minutes to prepare and

administer dose. Keep instructions with medication not in use or in a safe location.

• Only use needles provided. • Discontinue use 1 month before planning pregnancy.

DPP-4 Inhibitors

Take Home Points: DPP-4 inhibitorsEfficacy: 0.7-1% A1c reduction

- Impact post-prandial glucose - 4 weeks for maximum glucose

lowering effects

Impact on weight: Neutral

Other Side Effects/Concerns: - Acute pancreatitis

- Liver failure [alogliptin only]

Triplitt CL, Repas T, and Alvarez C. Diabetes. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy, 9th ed. New York: McGraw-Hill; 2014. Accessed Online: http://accesspharmacy.mhmedical.com.libproxy.siue.edu/ May 2015.

SGLT2 Inhibitors

Take Home Points: SGLT2 Inhibitors Efficacy: 0.7-1% A1c reduction

- Impacts fasting glucose

Impact on weight: Loss/Neutral

Other Side Effects/Concerns: - GFR < 30min/ml, ESRD , Dialysis

[Contraindicated]- GU infection

- Ketoacidosis

Triplitt CL, Repas T, and Alvarez C. Diabetes. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy, 9th ed. New York: McGraw-Hill; 2014. Accessed Online: http://accesspharmacy.mhmedical.com.libproxy.siue.edu/ May 2015.

Insulin medications and delivery devices

V-Go® Insulin Delivery SystemAgent Available as

Basal

NPH

Glargine U-100Glargine U-300Detemir

Lantus (Pen = Solostar)

Levemir (Pen=FlexTouch)

Basal-Prandial

Regular U-500 ????

Prandial

Regular Humulin RNovlooin R (??)

AspartGlulisineLispro

Novolog (Pen=???Apidra (Pen=??)Humalog (Pen=??)

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

Picture from Valertiras. http://www.go-vgo.com/what-is-vgo. Accessed on March 2015

Picture from Sanofi-Aventis. https://www.afrezza.com. Accessed on May 2015

Afrezza ® Inhaled Insulin

Picture from Valertiras. http://www.go-vgo.com/why-v-go. Accessed on May 2015

V-Go® Insulin Delivery System• Simple, discrete way to administer insulin• Do not have to travel with needles, pens,

or vials

• Maintenance Dose: Reach 50/50 split on daily basal-bolus insulin dose

V-GO Start Guide. http://www.go-vgo.com/sites/default/files/upload/hcp-start-guide.pdf Accessed on May 2015

23

V-Go® Insulin Delivery System

V-GO Start Guide. http://www.go-vgo.com/sites/default/files/upload/hcp-start-guide.pdf Accessed on May 2015

Afrezza ® Inhaled Insulin

• Indication • Age > 18 years old• Type 1 or 2 DM

• Contraindications• Chronic lung disease

(asthma, COPD)

• Precautions (history of/at risk for)

• Lung cancer• Diabetic ketoacidosis• Hypokalemia

Afrezza ® Inhaled Insulin

Efficacy: similar to prandial insulin options- Impact post-prandial glucose - 3-5 days for maximum glucose

lowering effects

Impact on weight: Weight Gain

Other Side Effects/Concerns:

• Cough (common)• Throat pain/irritation (common)• Hypoglycemia (similar to prandial

insulin options)• Fluid retention

Questions??