Page 1 This program has been supported by an educational grant from Sanofi Aventis Scott K. Stolte, Pharm.D. Associate Dean, Academic Affairs Bernard J. Dunn School of Pharmacy Shenandoah University Winchester, VA Speaker: Dr. Scott Stolte joined the faculty of the Bernard J. Dunn School of Pharmacy at Shenandoah University in 1998. Scott served as a faculty member and as Chair of the Department of Pharmacy Practice prior to assuming his position as Associate Dean for Academic Affairs. Dr. Stolte earned his Doctor of Pharmacy degree from Purdue University in West Lafayette, IN in 1997. Speaker Disclosure: Dr. Stolte has no actual or potential conflicts of interest in relation to this program This program has been supported by an educational grant from Sanofi Aventis PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Accreditation: Pharmacists 798-000-08-082-L01 Pharmacy Technicians 798-000-08-082-L01T Target Audience: Pharmacists and Pharmacy Technicians CE Credits: 1.0 Credit hour Expiration Date: 4/16/2011 Program Overview: This program will educate pharmacists on currently available insulin delivery options and information needed to counsel and treat patients while also improving medication adherence. Objectives: Review the pharmacological approaches to the management of type II diabetes to include their mechanisms of action comparative efficacy, pharmacokinetics and contraindications of agents Compare and contrast the different options for insulin delivery systems Describe the pharmacist s role in counseling and educating patients on drug treatment strategies, use of insulin delivery systems, and medication adherence to improve the quality of life and long-term maintenance of diabetes. This program has been supported by an educational grant from Sanofi Aventis Educational Objectives Review the pharmacological approaches, to include mechanisms of action, comparative efficacy, pharmacokinetics, and contraindications of the agents used to manage type 2 diabetes mellitus. Compare and contrast the different options for insulin delivery systems. Describe the pharmacist s role in counseling and educating patients on drug treatment strategies, use of insulin delivery systems, and medication adherence to improve the quality of life and long-term maintenance of diabetes.
Page 2 Pharmacotherapy for Type 2 Diabetes Mellitus Therapeutic Options Biguanides metformin Sulfonylureas Thiazolidinediones rosiglitazone, pioglitazone Glinides repaglitinide, nataglitinide Alpha-glucosidase inhibitors miglitol, acarbose DPP-4 inhibitors sitagliptan Incretin mimetic exenatide Amylin mimetic pramlintide Insulin Therapeutic Options Glucose Metformin Biguanide Improve insulin sensitivity at the liver (decreases hepatic glucose output) Enhances insulin sensitivity at the peripheral (muscle) tissues Presence of insulin is required
Page 3 Metformin UK-PDS Reduced macrovascularcomplications in obese patients Reduced all-cause mortality and risk of stroke compared to intensive therapy with insulin or a sulfonlyurea Reduced diabetes-related death and MI versus conventional therapy Monotherapy Reduce FBG by 60-80 mg/dl and HbA1C by 1.5-2.0% Other effects Increase HDL cholesterol (2%) Decrease triglycerides (16%) and LDL cholesterol (8%) Weight loss (2-5 kg or 4.4-11 lbs.) Should be part of therapy for ALL TYPE 2 pts w/o contraindications!!! Metformin - Combination therapy Sulfonylureas Further reduction of 25-30% in FBG and 2.2% in HbA1C Glitazones Further reduction of 0.9% in HbA1C Acarbose/miglitol Further reduction of 0.4% HbA1C Glinides Further reduction of 1.4% HbA1C Sitagliptan Further reduction of 0.7% HbA1C Exenatide Further reduction of 0.8% in HbA1C Insulin Further reduction of 1.7% in HbA1C Sulfonylureas Insulin secretagogues Enhance insulin secretion from beta-cells Leads to suppression of hepatic glucose production Increase sensitivity of pancreatic beta cells to glucose Second Generation drugs used primarily Glipizide, glyburide, glimepiride Sulfonylureas Treatment with equipotent doses of all agents will produce a similar response Dosing Lower doses in elderly and compromised renal or hepatic function Titrate every 1 to 2 wks Monotherapy Reduce FBG by 60-70 mg/dl and HbA1C by 1.5-2.0% Primary failure (15-25%) Secondary failure (5-7%/yr)
Page 4 Sulfonylureas Combination therapy Metformin Glitazones Further reduction of 1.1% in HbA1C Acarbose/miglitol Further reduction in HbA1C of 1.6% Sitagliptan Further reduction in HbA1C of 0.6% Exenatide Further reduction in HbA1C of 0.9% Insulin intermediate or long-acting Further reduction of 1.9% in HbA1C BIDS - Bedtime Insulin Daytime Sulfonylurea Sulfonylureas Positive predictors of response Newly diagnosed Type 2 (no indicators of Type 1) High fasting C-peptide Moderate fasting hyperglycemia (< 250 mg/dl) Extensively metabolized by CYP2C9 CYP2C9 has alleles Thiazolidinediones Activate PPARγ (peroxisome proliferator activator receptor γ) on fat and vascular cells Indirectly improves insulin sensitivity at the skeletal muscle and adipose tissue (and possibly the liver) by enhancing insulin action at the receptor and post receptor level Lowers plasma insulin levels Presence of insulin is required Thiazolidinediones Dosing Onset of action is SLOW (2-3 months) Maximum effect may take 3 to 4 months Can titrate after 12 weeks Monotherapy Reduce FBG by 60-70 mg/dl and HbA1C by 0.5-1.4% Other effects Pioglitazone: TG (10-20%), LDL, HDL Rosiglitazone: TG, LDL (5-15%), HDL Convert small dense LDL to larger, less atherogenic LDL
Page 5 Thiazolidinediones Combination Therapy Metformin Sulfonylureas Glinides Further reduction of 1.7% in HbA1C Sitagliptan Further reduction in HbA1C of 0.9% Exenatide Further reduction of 0.8% in HbA1C Insulin (> 30 units/day) Reduce insulin by 10-25% when FBG < 120 mg/dl Further reduction of 1.2% in HbA1C Glinides Enhance insulin secretion similar to sulfonylureas BUT, require the presence of glucose to stimulate insulin Help restore first-phase insulin secretion Compared to sulfonylureas Increased absorption and shorter half-life Glinides Dosing Up to 30 minutes prior to each meal If meal is skipped, do not take medication Titrate weekly Good to use in elderly and in renal impairment Monotherapy Reduce FBG by 20-30% and HbA1C by 0.8-1% of repaglinide > nateglinide Combination Metformin Thiazolidinediones Alpha-glucosidase inhibitors Competitively inhibits -glucosidases that break down starches in the small intestine Inhibits the breakdown of oligosaccharides and disaccharides into monosaccharides Delay in carbohydrate absorption and reduction in postprandial glucose levels
Page 6 Alpha-glucosidase inhibitors Dosing Take with first bite of meal Titrate to patient tolerance Monotherapy Reduce FBG by 0-15 mg/dl, PPBG by 40-50 mg/dl, and HbA1C by 0.3-0.8% Postprandial glucose improves more than fasting levels Rarely used as monotherapy Combination Therapy Sulfonylureas Metformin Increase in GI side effects Insulin Colesevelam Bile-acid sequestrant known as Welchol Recently approved for management of Type 2 diabetes Unknown Possible link between bile acid and glucose homeostasis? reduce amount of glucose absorbed Dosing 625mg tablets: 6 tablets daily or 3 tablets twice daily with meal or liquid Colesevelam Indicated for adjunctive therapy with metformin, sulfonylureas or insulin Reduces FBG by 13-15 mg/dl and HbA1C by 0.3 to 0.5% Reduces LDL by 12-16% Sitagliptin Dipeptidyl-peptidase-4 inhibitor known as Januvia Endogenous GLP-1 has a short half-life of < 2 minutes due to rapid inactivation by DPP-4 Block the breakdown of GLP-1 by inhibiting DPP-4 Potentates effects of endogenous GLP-1 Potentates glucose-dependent insulin secretion by beta-cells Suppresses glucagon secretion No to marginal slowing of gastric emptying Animal studies: improves islet survival and maintains betacell mass and function
Page 7 Sitagliptin Indicated for monotherapy or adjunctive therapy with metformin or thiazolidinediones Reduces FBG by 12-17 mg/dl, PPBG by 49-62 mg/dl, and HbA1C by 0.7 to 1% Need more long-term studies Only studied early in the treatment of Type 2 diabetes Exenatide Incretin mimetic known as Byetta Biosynthetic form of an incretin, GLP-1 (glucagon-like peptide) From the saliva for the gila monster lizard Potentates glucose-dependent insulin secretion by beta cells Suppresses inappropriately elevated glucagon secretion Slows gastric emptying Reduces food intake Restores first-phase response Animal studies: islet neogenesis, beta-cell proliferation, and increased beta-cell mass Exenatide Approved as adjunctive therapy to metformin, sulfonylureas, or TZDs Reduces FBG by 10-25 mg/dl, PPBG by 71 mg/dl, and HbA1C by 0.8 to 1.1% Weight reductions of 3.5 to 8 lbs at 1 yr and 11 lbs at 2.5 yrs at maximum dose (weight loss continues with duration of use) Pramlintide Amylin mimetic known as Symlin Slows gastric emptying, suppress glucagon secretion, and reduces appetite Reduces FBG by 28 mg/dl, PPBG by 24 mg/dl, and HbA1C by 0.4 to 0.7%, Weight reductions of 2.6 to 6 lbs
Page 8 Fast-acting Insulins Insulin Therapy Insulin Onset (minutes) Peak (hrs) Duration (hrs) Administration Lispro (Humalog) 15-30 1-2 3-4 Within 10 Aspart (NovaLog) 15-30 1-2 3-5 minutes of meal Glulisine (Apidra) 15-30 1-2 3-4 Regular (various) 30-60 2-3 3-6 30 min prior to meal Intermediate and Long-acting Insulins Insulin Therapies Insulin Onset (hrs) Peak (hrs) Duration (hrs) Administration NPH (various) 2-4 4-6 8-12 Twice daily* Glargine (Lantus) 4-5 --- 11 >24 Every 24 hrs* Detemir (Levemir) 2 6-9 6 23 Every 12-24 hrs* *Doses > 90 u/d should be split into 2 injections Detemir may require BID dosing in 33-50% If evidence of detemir or glargine wearing-off consider BID -controlled mid-injection pre-prandial BG and elevated pre-injection pre-prandial BG www.endotext.org
Page 9 Insulin Therapy Formulations Vials Pen devices SC pumps CSII (continuous subcutaneous insulin infusion) Insulin Therapy Vials: drawing up insulin dose Wash hands and sterilize top of insulin vial Use a new syringe and needle every time Draw air into the syringe equal to dosage Inject the air into the vial (do not remove syringe) Draw up dose into syringe Remove air bubbles (while syringe in vial) Tap syringe to get air bubbles to top of syringe Carefully eject air and draw in dose Insulin Therapy Pens: setting the dose Injecting insulin Determine injection site Clean skin Pinch skin fold Insert needle into skin fold at a 90 o angle Slowly inject the insulin by pushing the plunger or button all of the way Pull needle straight out Do NOT rub the area Discard syringe and/or needle Insulin Delivery Devices
Page 10 Insulin Delivery Pens Disposable Pens Humulin N, 70/30 Humalog 75/25, 50/50 Humalog Humalog KwikPen Novolin R, N Novolog 70/30 Novolog Levemir Lantus Solostar Kwik Pen (for humalog types of insulin) Reusable Pens HumaPen Memoir HumaPen Luxura HD NovoPen 3 NovoPen 4 NovoPen Junior Opticlik for Lantus and Apidra Disposable Insulin pens Lilly Pens Humalog Humalog 75/25 Humalog 50/50 Humulin 70/30 Humulin N Multiple dose device containing 3 ml (300 units) of U-100 insulin Up to 60 units per dose Dialed by single units (can be dialed in the opposite direction if needed to correct dose amount) Disposable Insulin Pens Kwik Pen Prefilled with Humalog types of insulin Same as Lilly pens Lightweight Easy hand position Disposable Insulin Pens Novo Nordisk Pens Novolog Mix 70/30, Novolog, Novo Levemir Contains 3mL (300 units) of insulin, up to 60 units per dose. Dose in 1-unit increments and can be turned backward and forward to adjust dose. Larger dialing window.
Page 11 Disposable Insulin Pens Sanofi Aventis pen Reusable Insulin Pens Lilly Pen Lantus SoloSTAR Similar to Flex Pens Contains 3mL (300 units) of insulin, up to 80 units per dose. 1-unit increments and can be turn forward and backward to adjust dose. HumaPen Memoir Only for use with Humalog and uses 3mL Cartridges (100IU/mL) Up to 60 units per dose and can be dialed forward or backward for adjusting dose. 1 unit increment doses Remembers last 16 doses Reusable Insulin Pens Lilly Pens Reusable Insulin Pens Novo Nordisk HumaPen Luxura HD Only for use with Humalog and uses 3mL Cartridges (100IU/mL) Up to 30 units per dose and can be dialed forward or backward for adjusting dose. ½ unit increment doses NovoPen 3 NovoPen 4 Used with Penfill 3mL insulin cartridges 2 to 70 units per dose in 1 unit increments NovoPen 3 cannot be dialed backwards (have to reset back to 0) NovoPen 4 can be dialed backwards and has a larger dose viewing screen
Page 12 Reusable Insulin Pens Novo Nordisk Reusable Insulin Pens Opticlik Pen NovoPen Junior Used with Penfill 3mL insulin cartridges 1 to 35 units per dose in ½ unit increments Cannot be dialed backwards (have to reset back to 0) Lantus and Apidra Uses 3mL Lantus or Apidra cartridges Up to 80 units per dose in 1 unit increments Structurally different Other Insulin Delivery Systems Novo Nordisk Key Features Other Delivery Pen Lilly Pen Key Features InnoLet Prefilled with 3 ml (300 units) of Novolin insulin Disposable and easy to read Up to 50 units per dose in 1 unit increments Byetta- incretin hormone 5mcg and 10mcg Contains 60 doses for 30 days of BID dosing Similar to other Lilly pens
Page 13 Pen Needles BD Pen Needles Make sure to use a new needle each time Prime the pen Do not store your pen with the needle attached Do not push the injection button until the needle is attached Pen Needles BD Ultra-Fine Mini Pen Needle may be used for: Patients who want the shortest pen needle available in the U.S. Patients who have needle phobia Children; very thin or muscular people Patients who don t' want to pinch-up Patients who use Exenatide BD Ultra-Fine Short Pen Needle may be used for: Most patients - it's a size that is appropriate for many people Patients who want a thinner 8mm needle* Patients who use OptiClik pen for Lantus and Apidra insulins Roles for the Pharmacist Medication/Device Selection and Education Which medication is best suited for a patient? Will patients take the medications they are prescribed? What concerns do the patients have about their diabetes regimen? Which blood glucose meter will best meet the patient s needs? Which insulin delivery system will best meet the patient s needs?