Hyperglycemia Management – Medication Therapy Janice Frueh, PharmD, BCPS Associate 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 Acarbose Miglitol Precose or generic Glyset Amylin analogue Pramlintide Symlin Biguanide Metformin Glucophage or generic Bile acid sequestrant Colesevelam WelChol DPP-4 inhibitors Alogliptin Linagliptin Saxagliptin Sitagliptin Nesina Tradjenta Onglyza Januvia Dopamine-2 agonist Bromocriptine Cycloset Glinides Nateglinide Repaglinide Starlix or generic Prandin Class Agent(s) Available as GLP-1 receptor agonists Albiglutide Dulaglutide Exenatide Exenatide XR Liraglutide Tanzeum Trulicity Byetta Bydureon Victoza SGLT2 inhibitors Canagliflozin Dapagliflozin Empagliflozin Invokana Farxiga Jardiance Sulfonylureas Glimepiride Glipizide Glyburide Amaryl or generic Glucotrol or generic Diaeta, Glynase, Micronase, or generic Thiazolidinediones Pioglitazone Rosiglitazone Actos or genetic Avandia 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 System Agent Available as Basal NPH Glargine U-100 Glargine U-300 Detemir Lantus (Pen = SoloSTAR) Levemir (Pen=FlexTouch) Basal-Prandial Regular U-500 Prandial Regular Humulin R Novlooin R Aspart Glulisine Lispro Novolog (Pen=FlexPen) Apidra (Pen = SoloSTAR) Humalog (Pen=KwikPen) Afrezza ® Inhaled Insulin 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

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

At 3 month f/u = 6 choices for medication management Antihyperglycemic therapy in type 2 diabetes: general recommendations. 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 Silvio E. Inzucchi et al. Dia Care 2015;38:140-149 ©2015 by American Diabetes Association

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

Non-insulin dependent Produce Glucose Kidney Liver Normal Glucose Levels Eliminate Glucose Non-insulin dependent Brain Neurons Insulin dependent Liver Muscle 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 Metformin Thiazolidinediones Blunted incretin effect GLP-1 receptor agonists DPP-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 Acarbose Miglitol Precose or generic Glyset Amylin analogue Pramlintide Symlin Biguanide Metformin Glucophage or generic Bile acid sequestrant Colesevelam WelChol DPP-4 inhibitors Alogliptin Linagliptin Saxagliptin Sitagliptin Nesina Tradjenta Onglyza Januvia Dopamine-2 agonist Bromocriptine Cycloset Glinides Nateglinide Repaglinide Starlix or generic Prandin Class Agent(s) Available as GLP-1 receptor agonists Albiglutide Dulaglutide Exenatide Exenatide XR Liraglutide Tanzeum Trulicity Byetta Bydureon Victoza SGLT2 inhibitors Canagliflozin Dapagliflozin Empagliflozin Invokana Farxiga Jardiance Sulfonylureas Glimepiride Glipizide Glyburide Amaryl or generic Glucotrol or generic Diaeta, Glynase, Micronase, or generic Thiazolidinediones Pioglitazone Rosiglitazone Actos or genetic Avandia 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..

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 inhibitors Efficacy: 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 System Agent Available as Basal NPH Glargine U-100 Glargine U-300 Detemir Lantus (Pen = Solostar) Levemir (Pen=FlexTouch) Basal-Prandial Regular U-500 ???? Prandial Regular Humulin R Novlooin R (??) Aspart Glulisine Lispro Novolog (Pen=??? Apidra (Pen=??) Humalog (Pen=??) Afrezza ® Inhaled Insulin 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

Picture from Valertiras. http://www. go-vgo. com/why-v-go 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

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??