INJECTABLE THERAPY FOR THE TREATMENT OF DIABETES ARSHNA SANGHRAJKA DIABETES SPECIALIST PRESCRIBING PHARMACIST
OBJECTIVES EXPLORE THE TYPES OF INSULIN AND INJECTABLE DIABETES TREATMENTS AND DEVICES AVAILABLE GAIN AN UNDERSTANDING OF THE TYPES OF INSULINS AND INJECTABLE TREATMENTS AVAILABLE AND THEIR PLACE IN TYPE 2 DIABETES TREATMENT REVIEW INSULIN ADMINISTRATION TECHNIQUES AND EMERGENCY USE OF GLUCAGON YOUR ROLE IN TREATING DIABETES PATIENTS TOP TIPS FOR DIABETES MURS
INJECTABLE PRODUCTS
WHERE DO THEY SIT WITH CURRENT NICE GUIDANCE?
INSULIN OR GLP-1 AGONISTS
GLP-1 AGONISTS
PHYSIOLOGY OF POSTPRANDIAL GLUCOSE REGULATION Meal ❶ ❷ Insulin Rising plasma glucose stimulates pancreatic β-cells to secrete insulin 1 Glucagon Insulin Glucagon Gastric emptying Plasma glucose inhibits glucagon secretion by pancreatic α-cells 1 PPG ❸ Gastric emptying Delaying and/or slowing gastric emptying is a major determinant postprandial glycaemic excursion 2 of Hepatic glucose output + Glucose uptake PPG = postprandial glucose 1 DeFronzo RA. Med Clin North Am 2004;88:787-835 2 Horowitz M et al. Diabet Med 2002;19:177-94
Glucagon-like peptide-1 and incretin effect β-cell α-cell Food intake GLP-1 Incretin effect Pancreatic islet GLP-1 is a major intestinal hormone mediating the incretin effect GLP-1 potentiates insulin release and reduces glucagon secretion in glucose-dependent manner Adapted from Drucker D. Diabetes Care. 2003;26:2929-2940; and Wang Q, et al. Diabetologia. 2004;47(3):478-487.
THE INCRETIN EFFECT oral glucose load (50 g) iv glucose infusion 15 Plasma glucose 270 80 Plasma insulin 10 mmol/l 5 180 mg/dl 90 60 mu/l 40 20 Incretin effect 0 10 5 60 120 180 Time (min) 0 0 10 5 60 120 180 Time (min) Insulin response is greater following oral glucose than iv glucose, despite similar plasma glucose concentrations Nauck MA et al. Diabetologia 1986;29:46 52. Healthy volunteers n=8
GLP-1 MODULATES NUMEROUS FUNCTIONS GLP-1: Secreted upon the ingestion of food Promotes satiety and reduces appetite Alpha cells: Postprandial glucagon secretion Beta cells: Enhances glucosedependent insulin secretion Liver: Glucagon reduces hepatic glucose output Stomach: Helps regulate gastric emptying Data from Flint A, et al. J Clin Invest. 1998;101:515-520; Data from Larsson H, et al. Acta Physiol Scand. 1997;160:413-422 Data from Nauck MA, et al. Diabetologia. 1996;39:1546-1553; Data from Drucker DJ. Diabetes. 1998;47:159-169
GLP-1 IS NORMALLY DEGRADED BY THE DPP-4 ENZYME MEAL DPP-4 inhibitor DPP-4 Enzyme GLP-1 agonist (resistant to DPP-4 degradation) Release of Active GLP-1 Rapid Inactivation Inactive GLP-1
GLP-1 Actions in Peripheral Tissue Heart Brain Neuroprotection Appetite Gastric emptying Stomach Stomach Cardioprotection Cardiac output GI Tract GLP-1 Liver _ Insulin secretion β-cell neogenesis Glucose production Drucker DJ. Cell Metab. 2006;3:153-165. Muscle + Glucose Uptake β-cell apoptosis Glucagon secretion
INCRETIN-BASED THERAPIES GLP-1 RECEPTOR AGONISTS AND DPP-4 INHIBITORS GLP-1 receptor agonists Short-acting BD Exenatide (Byetta) OD Lixisenatide (Lyxumia) Long-acting OD Liraglutide* (Victoza) Longer-acting QW Exenatide (Bydureon) Dulaglutide (Trulicty) DPP-4 inhibitors Sitagliptin Vildagliptin Saxagliptin Linagliptin OD BD OD OD Subcutaneous injection Tablets Mimics endogenous GLP-1 Enhance endogenous GLP-1 *Human GLP-1 analogue, others are exendin-based DPP-4 = dipeptidyl peptidase-4; OD = once daily; BD = twice daily; QW = once weekly Drucker DJ, Nauck MA. Lancet 2006;368:1696 1705
Choice of GLP-1 receptor agonist: short acting versus long acting The pharmacological profile and half-life of a GLP-1 receptor agonist influences its effects on postprandial and basal (fasting) glycaemia SHORT ACTING GLP-1 receptor agonists Lixisenatide OD, Exenatide BD or LONG ACTING GLP-1 receptor agonists Liraglutide OD, Exenatide/Dulaglutide QW Effect on FPG Effect on PPG Effect on FPG Effect on PPG FPG = fasting plasma glucose PPG = postprandial glucose Fineman MS et al. Diabetes Obes Metab 2012;14:675-88
GLP-1 RECEPTOR AGONISTS Contraindications Black Box Warning Adverse Effects Monitoring Interactions Family history of medulary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2* Risk of thyroid tumors (shown in animal models)* Nausea, vomiting, diarrhea, decreased appetite, weight loss, pancreatitis FBG, HBA1c, Serum Creatinine, Kidney Function - Agents that induce hypoglycemia - GLP-1 agonists may reduce rate of absorption of orally administered drugs Clinical pearls - Low hypoglycemia risk - Injectable - Avoid in patients with gastroparesis - May need to reduce dose of insulin and/or secretagogues - Pregnancy category C - All available as SC pens - 1-1.5 % in A1C
SIDE EFFECTS: GLP-1 RECEPTOR AGONISTS AND DPP-4 INHIBITORS GLP-1 Receptor Agonists DPP-4 Inhibitors Side effects Gastrointestinal Well tolerated Weight Administration Other cardiac risk factors > 85% patients lose weight Twice-daily injection Triglycerides HDL Blood pressure Weight neutral Oral, once daily Unknown Davidson JA. Cleve Clin J Med. 2009;76(suppl5):S28-S38.
GLP-1 RA STABILITY GLP-1 RA Stability Once Opened at Room Temperature Byetta (Exenatide IR) 30 Bydureon (Exenatide ER) Victoza (Liraglutide) 28 30 Trulicity (Dulaglutide) 14
GLP1 AGONIST AND COST PER MONTH LIXISENATIDE 20MG OD; 54.14 EXENATIDE (10ΜG BD); 68.24 BYDURON; 73.76 LIRAGLUTIDE (1.2MG OD); 78.48. LIRAGLUTIDE (1.8MG OD); 117.72 DULAGLUTIDE (1.5MG) ; 73 PM IDEGLIRA (50 DOSE DAILY); 159.22
HOW TO USE GLP1-AGONISTS WITH ORAL TREATMENT; USE LEAST EXPENSIVE AGENT (LIXISENTATIDE). CONTINUE WITH METFORMIN AND/OR PIOGLITAZONE. ADD SGLT2 INHIBITOR IF POST-PRANDIAL HYPERGLYCAEMIA. MOVE FROM LIXISENATIDE/EXENATIDE TO A GLUTIDE; IF NAUSEOUS OR SUB-OPTIMAL RESPONSE. TRANSFER TO BIPHASIC INSULIN (HUMULIN M3); IF NO WEIGHT LOSS OR IMPROVED GLYCAEMIC CONTROL. WITH OD HUMAN BASAL (HUMULIN I); WITH DOSE INCREASING BY 10% ALTERNATE DAYS TO REDUCE FBG < 6MMOL.
INSULIN
INSULIN MOA Dosing Adverse Effects Monitoring Interactions Clinical pearls Insulin is endogenously produced in the beta islet cells of the pancreas and allows glucose to enter cells to be used as energy Initiate basal (long-acting) insulin at 0.2 units/kg at bedtime and increase by 2 units every 2-3 days until FBG levels are at goal Weight gain, injection site reactions, lipoatrophy, lipohypertrophy, hypoglycemia FBG, HBA1c Any agents which promote hypoglycemia - Most effective method to lower HBA1c - 1.5-3.5 % in HBA1c
INSULIN: DURATION OF ACTION Insulin: Duration of Action
INSULIN DEGLUDEC (TRESIBA ) DURATION: > 42 HOURS (DOSED ONCE DAILY) STEADY STATE ACHIEVED AFTER 3-4 DAYS OF THERAPY HALF LIFE ~ 25 HOURS CAUTION WHEN PATIENTS ARE SICK
INSULIN DEGLUDEC (TRESIBA )
HUMULIN R U-500 5X AS CONCENTRATED AS HUMULIN R U-100 SLIGHTLY DELAYED ONSET AND LONGER DURATION OF ACTION PRESCRIBED IN UNITS OF INSULIN INSTRUCTIONS FOR ADMINISTRATION VARY BY SYRINGE USED U-100 SYRINGE, DIVIDE PRESCRIBED DOSE BY 5 TUBERCULIN SYRINGE, DIVIDE PRESCRIBED DOSE BY 500 RISK OF OVERDOSE IF USED INCORRECTLY http://www.medscape.com/viewarticle/857811
OTHER CONCENTRATED INSULINS AGENTS: U-300 GLARGINE (TOUJEO) U-200 DEGLUDEC (TRESIBA) U-200 LISPRO (HUMALOG) PRESCRIBED IN UNITS OF INSULIN MUST CALCULATE WHAT MARKING PATIENT WILL DRAW UP TO USING SYRINGE ALLOW SMALLER VOLUME ADMINISTRATION
ADMINISTERING INSULIN USING A PEN http://pi.lilly.com/us/humalog-kwikpen-um.pdf
http://pi.lilly.com/us/humalog-kwikpen-um.pdf PREPARING THE INSULIN PEN
http://pi.lilly.com/us/humalog-kwikpen-um.pdf PRIMING THE INSULIN PEN
http://pi.lilly.com/us/humalog-kwikpen-um.pdf SELECTING THE INSULIN DOSE
ADMINISTERING THE INSULIN DOSE http://pi.lilly.com/us/humalog-kwikpen-um.pdf
PREPARING THE PEN FOR FUTURE USE http://pi.lilly.com/us/humalog-kwikpen-um.pdf
PREPARING THE PEN FOR FUTURE USE http://pi.lilly.com/us/humalog-kwikpen-um.pdf
NEEDLES NEEDLES SHOULD NOT BE RE- USED!
INJECTING INSULIN INSERT NEEDLE AT A 90º ANGLE (45º FOR VERY THIN) DEPRESS PLUNGER HOLD FOR 5 SECONDS WITHDRAW NEEDLE DISPOSE IN SHARPS CONTAINER ROTATE INJECTION SITES! https://www.bd.com/resource.aspx?idx=3260 http://www.drugs.com/cg/giving-an-insulin-injection.html
http://www.lillyglucagon.com/important-safety-information GLUCAGON EMERGENCY KIT
http://www.lillyglucagon.com/important-safety-information GLUCAGON EMERGENCY KIT (CONTINUED )
OTHER CONSIDERATIONS DISPOSAL OF SHARPS DRIVING AND THE DVLA TRAVEL SICK DAY RULES HYPOGLYCAEMIA
ADHERENCE BARRIERS TO INJECTABLE AGENTS COST UNWILLING TO INJECT FEAR OF HYPOGLYCEMIA FORGETFULNESS LOW HEALTH LITERACY
THANK YOU! http://co9to25.org/
USEFUL RESOURCES DIABETES PATIENT LEAFLETS ON HYPOGLYCAEMIA, DRIVING AND TRAVEL: HTTP://TREND-UK.ORG/ DIABETES UK WEBSITE: HTTPS://WWW.DIABETES.ORG.UK/ TIMESULIN DEVICES: HTTPS://TIMESULIN.COM/ INFORMATION ON THE SPC OF INSULINS AND GLP1 AGONISTS: HTTP://WWW.MEDICINES.ORG.UK/EMC/ NICE GUIDANCE ON TYPE 2 DIABETES IN ADULTS: HTTPS://WWW.NICE.ORG.UK/GUIDANCE/NG28
USEFUL RESOURCES DIABETES PATIENT SELF CARE LEAFLET: HTTP://WWW.NHS.UK/CONDITIONS/DIABETES- TYPE2/PAGES/LIVING-WITH.ASPX THINK KIDNEYS WEBSITE: HTTPS://WWW.THINKKIDNEYS.NHS.UK/ SICK DAY RULES CARD AND LEAFLET (SCOTTISH) - HTTP://WWW.SCOTTISHPATIENTSAFETYPROGRAMME.SCOT.NHS.UK/P ROGRAMMES/PRIMARY-CARE/MEDICINE-SICK-DAY-RULES-CARD DIABETES DRUG COMPANY PROFILES AND CONTACTS: HTTPS://DIABETES.CO.UK/DIABETES-INDUSTRIES.HTML