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Rapid- Acting 5-15 minutes 0.5-3 hours 3-5 hours Meal should be available before administering, ideally taking within 10 minutes of eating). Good in refrigerator (36-46 F) until expiration date. Protect from light. May be mixed with NPH only (draw the rapid acting insulin first then NPH and use immediately). Should be used in regimens with intermediate or long- acting insulin when giving multiple daily injections (MDI). Clear and colorless. Unless for correction, rapid- acting insulin should not be taken if not eating a meal. Insulin Aspart (NovoLog) Novo Nordisk www.novolog.com 1-3 hours Available in FlexPen, NovoPen Echo (delivers 0.5 units and has memory of last dose and time passed since last injection) or vial. May be substituted for insulin lispro (Humalog) and glulisine (Apidra). Approved for use in pregnancy (category B). Both pen and vial good for 28 days at room temperature (<86 F). Novo Nordisk offers instant savings card ($25 per refill for 2 years) for non- government insurance payers (Medicare and Medicaid).

Insulin Lispro (Humalog) 30-90 minutes Available in KwikPen or vial. May be substituted for insulin aspart (NovoLog) and glulisine (Apidra). www.humalog.com Approved for use in pregnancy (category B). Both pen and vial good for 28 days at room temperature (<86 F). Insulin Glulisine (Apidra) 40-120 minutes Available in SoloStar Pen or vial. May be substituted for insulin aspart (NovoLog) or lispro (Humalog). Sanofi Not well studied during pregnancy (category C). www.apidra.com Both pen and vial good for 28 days at room temperature (<77 F). Pen dials up from 1 to 80 U in a single injection. Short acting 30-60 minutes 1.5-4 hours 4-8 hours Should be taken 30 minutes before eating. May be mixed with NPH (draw Regular insulin first). Clear and colorless. Approved for use in pregnancy (category B). Good in refrigerator (36-46 F) until expiration date. Protect from light. Usually preferred in IV drip.

Regular 30-60 minutes 1.5-4 hours 4-8 hours Only available in a vial. Novolin R (U- 100) Novo Nordisk May be mixed with NPH (draw Regular insulin first). Good for 28 days at room temperature (<86 F). Generic versions available (ReliOn/Novolin R)- $25 at Walmart. Should not be taken if not eating a meal. Walmart (ReliOn) Humulin R (U- 100) www.humulin.com/humulin- r- u- 100.aspx Only available in a vial. May be mixed with NPH (draw Regular insulin first). Good for 31 days at room temperature (<86 F). Should not be taken if not eating a meal. 10 ml vial

Humulin R (U- 500) www.humulin.com/ Lasts up to 24 hours (chance for hypoglycemia 18-24 hours after injection) Only available in a vial; use either volumetric (Tuberculin) or U- 100 insulin syringe. Unable to mix with other insulin. Five times stronger than U- 100 (reduces volume by 80%). 20mL vial Given to patients who are very insulin resistant. Patient may be appropriate if TDD >200 units/day. (One vial of U- 500 contains as many units of insulin as 10 vials of U- 100 insulin) Normally dose BID before breakfast & supper but may be taken before each meal. Action is similar to NPH. Good for 31 days at room temperature (<86 F). Intermediate Acting 1-3 hours 4-10 hours 10-16 hours typical Usually dosed BID but may be at bedtime only to but may last up to 20- correct FBG. 24 hours May be mixed with rapid- acting insulin, Novolin R U- 100 and Humulin R U- 100. Cloudy and milky in color; must mix before each use. Approved for use in pregnancy (category B); often preferred for insulin naive moms because small peak seems to better help with FBG control. Good in refrigerator (36-46 F) until expiration date. Protect from light. Usually dosed BID but may be taken only at bedtime to correct FBG.

NPH (Novolin N) Novo Nordisk Only available in vial. Good for 42 days at room temperature (<77 F). Generic versions available (ReliOn/Novolin N)- $25 at Walmart. Walmart (ReliOn) NPH (Humulin N) Available in KwikPen or vial. Vial: good for 31 days at room temperature (<86 F). www.humulin.com/humulin- n.aspx Pen: good for 14 days at room temperature (<86 F). Long- Acting Usually taken at bedtime but can be taken in the morning if worried about nocturnal hypoglycemia or twice a day if looks like wearing off (ideal to space 12 hours between injections). Best to take at same time daily. Clear and colorless. Good in refrigerator (36-46 F) until expiration date. Protect from light.

Insulin Glargine (Lantus) 1-2 hours None 20-24 hours Available in SoloStar pen or vial. Both pen and vial good for 28 days at room temperature (<86 F). Sanofi Pen dials up from 1 to 80 U in a single injection. Not studied for use during pregnancy (category C). www.lantus.com If changing from once daily NPH to Lantus, keep dose the same; if changing from twice daily NPH to Lantus, recommend to reduce dose by 20% to reduce risk of hypoglycemia. Dose can be kept the same if changing from determir (Levemir) to glargine (Lantus). Insulin Determir (Levemir) 1-2 hours Relatively flat; possible small peak 6-8 hours. 12-20 hours, but may Available in FlexTouch pen (no push button last for 24 hours in extension; replacing FlexPen) or vial. some patients. Novo Nordisk www.levemir.com Both pen and vial good for 42 days at room temperature (<86 F). Pen dials up from 1 to 80 U in a single injection. Approved for use during pregnancy (category B). If changing from once daily NPH to Levemir, keep dose the same; if changing from twice daily NPH to Levemir, recommend to reduce dose by 20% to reduce risk of hypoglycemia. Dose can be kept the same if changing from glargine (Lantus) to determir (Levemir). Novo Nordisk offers instant savings card ($25 per refill for 2 years) for non- government insurance payers (Medicare and Medicaid).

Pre- Mixed Usually dosed BID at breakfast and dinner. Dual peak for action to try to control meals and overnight BG. Cloudy and milky in color; must mix before each use; helps to eat on schedule and time 2nd meal 4-6 hours later. Good in refrigerator (36-46 F) until expiration date. Protect from light. 70% NPH and 30% Regular 30-60 minutes 2-12 hours 10-18 hours. Novolin 70/30 only available in vial; Generic versions available (ReliOn/Novolin 70/30)- $25 at Walmart. (Novolin 70/30) (Humulin 70/30) Good for 10 days at room temperature (<86 F). Take 30 minutes before eating. Humulin 70/30 comes in KwikPen or vial. Pen only good for 10 days at room temperature but vial good for 31 days at room temperature (<86 F). www.humulin.com/humulin- 70-30.aspx Take 30 minutes before eating. Humulin 50/50 was discontinued in 2010.

70% insulin aspart protamine suspension and 10-15 minutes 1-4 hours 10-16 hours Available in FlexPen or vial. 30% insulin aspart (NovoLog Mix 70/30) Vial good for 28 days at room temperature (<86 F). Pen good for 14 days at room temperature (<86 F). Novo Nordisk www.novologmix70-30.com/ When mixing insulin, need to have at least 12 units left in pen to mix well. If not, new pen use recommended. Take within 15 minutes of eating a meal. Novo Nordisk offers instant savings card ($25 per refill for 2 years) for non- government insurance payers (Medicare and Medicaid). 70% insulin lispro protamine suspension and 10-15 minutes 1-4 hours 10-16 hours For both Humalog 75/25 and Humalog 50/50: 30% insulin lispro (Humalog 75/25) Available in KwikPen or vial. Take within 15 minutes of eating a meal. 50% insulin lispro protamine suspension and 50% insulin lispro (Humalog 50/50) www.humalog.com/humalog- kwikpen- insulin- pen.aspx 1-5 hours 10-16 hours Vial: good for 28 days at room temperature (<86 F). Pen good for 10 days at room temperature (<86 F).

V- Go 5-15 minutes No peak but have option to bolus meals in 2 Unit increments, up to 36 units daily for each V- Go 24 hours (delivers continuous basal rate for 24 hours) V- Go is attached to the skin and whole device is changed and disposed of daily. Disposable Insulin Delivery Device (Uses vials of rapid- acting insulin; tested with Humalog and NovoLog; not tested with Apidra) Comes in different delivery options but patient must be able to tolerate minimum basal rate of 20 units/day since unable to adjust basal rate: Valeritas V- Go 20 (basal rate 20 units/day (0.83 U/hr) and bolus up to 36 units in 2- unit increments). V- Go 30 (basal rate 30 units/day (1.25 U/hr) and bolus up to 36 units in 2- unit increments). V- Go 40 (basal rate 40 units/day (1.67 U/hr) and bolus up to 36 units in 2- unit increments). www.go- vgo.com/ Insulin is filled into each separate V- Go delivery device through the EZ Fill product (transfers insulin from the vial into the V- Go ); patient gets new EZ Fill with each 30- day V- Go supply. Uses U- 100 fast- acting insulin and ordered for a 30- day supply (patient needs 2 vials each month for V- Go 20 and 3 vials each month for V- Go 30 and 40). May be beneficial for patients on <100 units insulin daily (usually recommended patient's total daily dose of insulin is reduced by 25-30%). May be beneficial for patients that do not want hassle of multiple injections and are not well controlled on basal insulin (at 50+ Units) and oral meds. Can be worn on abdomen or back side of the arm.

Afrezza 5-15 minutes 0.5-3 hours 3-5 hours Inhaled insulin taken at the beginning of a meal. (insulin human) inhalation powder Dispensed in 4 unit (blue) and 8 unit (green) cartridges; able to take maximum 24 units per meal (3 cartridges per use). This is a rapid- acting insulin and needs to be paired with long- acting (basal) insulin. Inhaled insulin approved by FDA but not available to market yet. Lung function needs to be assessed before starting (spirometry, a physical and medical history); Not recommended for those who have chronic lung disease (asthma or COPD) or people who smoke or recently stopped smoking. MannKind looks to be partnering with Sanofi for marketing. Not studied with pregnancy (category C). Inhaler can be stored in refrigerator or at room temperature (30-77 F) but needs to be at room temperature before use. Inhaler must be replaced every 15 days. Cartridges are sold in foil package with 2 sealed blister cards that contain 5 strips of 3 cartridges (i.e. 30 cartridges per foil package). Unopened foil packages are good in refrigerator (36-46 F) until expiration date but cartridges being used need to sit at room temperature at least 10 minutes before use. Unopened blister card and strips good for 10 days at room temperature (<77 F). Opened strips good for 3 days at room temperature (<77 F).

Special Notes: Pen Needles: Syringes: Injection Tips: Insulin's mechanism of action: Most vials of insulin contain 1000 Units (10 ml). The higher the gauge for pen needle, the thinner the pen needle. 1/3 ml syringe = 30 units Always wash hands and injection site. The primary activity of insulin is the regulation of glucose metabolism. Insulin exert their specific action through binding to insulin receptors. This lowers blood glucose by facilitating cellular uptake of glucose into receptor- bound insulin skeletal muscle and adipose tissue and by inhibiting the output of glucose from the liver. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis, and enhances protein synthesis. Most pens contain 300 units (3 ml) and 5 pens come to a box (pharmacy cannot split boxes). Needle length: 31G and either 4 or 5 mm appropriate for most patients using insulin. 1/2 ml syringe = 50 units Rotate injection sites to prevent lipodystrophy, which may interfere with insulin absorption For safety, patients starting insulin should notify the department of motor vehicles about insulin use and should start carrying rapid- acting source of glucose and medical ID at all times incase of hypoglycemia. Pen needles and insulin syringes need to be ordered separately from prescription. Most people do not need to pinch skin unless 1 ml syringe = thin and worried about 100 units going into muscle. Can be injected in fatty tissue in abdomen, outer thighs, upper arm Discuss appropriate sharps disposal. and in buttock; may see better absorption in abdomen. Prime insulin pen before each use (2 unit air shot). New needle for each injection; do not store with needle. Last Revised: 10/2014