What s New in Diabetes Medications Jena Torpin, PharmD 1
Objectives Discuss new medications in the management of diabetes Understand the mechanism of the medications discussed Understand the side effects of the medications discussed 2 Acknowledgement: Some slides adapted/used with permission from Dr. Heather Blue s Presentation, Diabetes Medication Update, 3/5/2015
Review of Diabetes Types of Diabetes o o Type 1: complete insulin deficiency Type 2: decreased insulin secretion & insulin resistance Hepatic Glucose Production Blood Glucose Pancreatic Insulin secretion Peripheral Glucose Uptake 3 Cefalu, Diabetes Care, 2016; Khardori R, www.medscape.org, 2015
Review of Diabetes- Diagnosis Test Fasting Plasma Glucose (FPG) Dx Criteria 126 mg/dl 2 Hour Plasma Glucose 200 mg/dl A1C 6.5% Random Glucose 200 mg/dl + symptoms of hyperglycemia/crisis 4 Cefalu, Diabetes Care, 2016; Khardori R, www.medscape.org, 2015
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 5 Cefalu, Diabetes Care, 2016
Review of Diabetes- Treatment of Type 2 Diabetes 1 st Line 2 nd Line Metformin Oral Agent GLP-1 Analog Insulin Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT2 Inhibitor 6 Cefalu, Diabetes Care, 2016
Previous Toolbox Metformin Sulfonylureas Thiazolidinediones Insulin Meglitinides Alpha-glucosidase inhibitors 7
Previous Toolbox- Biguanide (Metformin) Mechanism: Hepatic Glucose Production Insulin Sensitivity 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 8 Cefalu, Diabetes Care, 2016; UpToDate; Bahal O Mara, Pharmacist s Letter, 2015
Previous Toolbox- Sulfonylureas (Glyburide, Glipizide, Glimepiride) Mechanism of Action: pancreatic release of insulin Effectiveness: Decreases A1C by 1-1.5% Dosing: Start low and go slow in elderly patients and those with hepatic or renal disease Adverse Drug Events: hypoglycemia Cost: $4 list 9 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
Previous Toolbox- Thiazolidinediones (TZDS- Pioglitazone, Rosiglitazone) Mechanism of Action: Increased insulin sensitivity Effectiveness: Decreases A1C by 1-1.5% Dosing: titrate cautiously- monitor for signs of heart failure Adverse Drug Events: Edema, heart failure, fractures, increased LDL (rosiglitazone) Cost: Low 10 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; UpToDate
Previous Toolbox-Insulin 11 Micromedex, Lexicomp, UpToDate
Previous Toolbox-Insulin Profiles 12 Micromedex, Lexicomp, UpToDate
Previous Toolbox Efficacy/A1C reduction Hypoglycemia Risk Metformin Sulfonylurea TZD Insulin High: 1-1.5% High: 1-1.5% High: 1-1.5% Highest: 1.5-3.5% 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 13 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
New Diabetes Medications 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 14
Sodium Glucose Co-Transporter 2 Inhibitors 15
Sodium-glucose transporter 2 inhibitors Drugs: o canagliflozin (Invokana ) o dapagliflozin (Farxiga ) o empagliflozin (Jardiance ) Mechanism: Prevents glucose from being reabsorbed by kidneys, resulting in glucose loss into urine 16 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; UpToDate
Effectiveness of SGLT2 Inhibitors 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 17 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; Nauck, Drug Des Devel Ther, 2014
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 18 Micromedex
Adverse Effects of SGLT2 Inhibitors Urinary tract infections (~5%) Genital infections (up to ~11%) Renal impairment Polyuria (~5%) Hypovolemia Increased LDL Bladder cancer? 19 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; Micromedex, UpToDate
Dipeptidyl Peptidase-4 Inhibitors 20
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) 21 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
Endogenous Incretin Mechanism of Action Insulin Secretion/Synthesis Glucagon secretion 22 Henry RR, www.medscape.org, 2009
23 Image: Adapted from Henry RR, www.medscape.org, 2009
Effectiveness of DPP-4 Inhibitors Reduced A1C by 0.5-1%; some believe to more around 0.7% No hypoglycemia (monotherapy) Weight neutral 24 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
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 <30 6.25 mg daily 25 UpToDate
Adverse Effects of DPP4-Inhbitors Potential for pancreatitis May increase risk of hospitalizations due to heart failure Immune mediated dermatological/angioedema side effects 26 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
Glucagon-Like Peptide-1 (GLP-1) Agonist 27
Glucagon-like peptide 1 receptor agonists Short Acting o Exenatide (Byetta )-- twice daily o Liraglutide (Victoza ) -- once daily Long Acting Weekly dosing o Albiglutide (Tanzeum ) o Exenatide extended release (Bydureon ) o Dulaglutide (Trulicity ) Mechanism: bind to GLP-1 receptors 28 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; UpToDate
29 Image: Adapted from Henry RR, www.medscape.org, 2009
Effectiveness Reduced A1C by 1-1.5% Few/no hypoglycemic events (monotherapy) Weight loss (~1-2.7kg) Some CV risk reduction 30 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; Micromedex
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) 31 UpToDate,
Adverse effects of Glucagon-like peptide 1 receptor agonists Boxed warning: thyroid C-cell tumors GI Side Effects: Nausea/vomiting/diarrhea: 10-50% Potential for pancreatitis Renal dysfunction Injection site reactions 32 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015; Micromedex
New Diabetes Medications Efficacy/A1C reduction Hypoglycemia Risk DPP-4 Inhibitor SGLT2 Inhibitor GLP-1 Receptor Agonist Intermediate: 0.5-1% Intermediate: 0.5-1% Low Low Low Weight Neutral Loss Loss Side Effects Rare Genitourinary, dehydration Costs High High High High: 1-1.5% GI 33 Cefalu, Diabetes Care, 2016; Bahal O Mara, Pharmacist s Letter, 2015
34 Insulin
Inhaled Insulin Inhaled insulin Afrezza regular insulin 4 unit, 8 unit, and 12 unit cartridges Dosing: Injected Prandial Insulin Up to 4 units Afrezza Dose 4 units 5-8 units 8 units 9-12 units 12 units 13-16 units 16 units 17-20 units 20 units 21-24 units 24 units Side Effects: hypoglycemia, cough, throat pain 35 Afrezza, Prescribing Information, 2014
Other/New Insulin Formulations 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 36 UpToDate
Take Away Points Many new medications with novel mechanisms Mainstay of therapy while patients are in the hospital still remains insulin therapy 37
thank you! Jena.Torpin@allina.com